ALBERT

Notes: (+)-Pisiferic acid (1), an antibiotic active against Gram-negative and Gram-positive bacteria, was synthesized starting from dehydroabietic acid (2) or abietic acid (26). The terpene ring system was functionalized and a Barton reaction used to oxidize Me(20). The intermediates of this photochemical reaction were isolated and characterized.

Notes: Oligonucleotides containing 4-aminobenzimidazole 2′-deoxyribofuranoside (1,3-dideaza-2′-deoxyadenosine; c1c3Ad, 1) were synthesized. For this purpose, various NH2-protecting groups were investigated, and the [(9H-fluoren-9-yl)methoxy]carbonyl group was selected for phosphoramidite protection (→ 4c). Apart from the phosphoramidite 3, the phosphonate 2 was prepared. Compound 1 was incorporated in a homooligonuclectide as well as in oligomers containing naturally occurring nucleosides. The Tm values and the thermodynamic data of various duplexes (11 · 10, 17 · 10, 18 · 10) containing 4-aminobenzimidazole were determined. Although d[(c1c3A)20] (11) does not form a Hoogsteen duplex with d(T20) (10) as observed with d[(c1A)20], it destabilizes the Watson-Crick duplexes to a much smaller extent than it was expected from a bulged loop structure. Apparently, 4-aminobenz-imidazole interacts with regular nucleoside residues within a Watson-Crick duplex structure, most likely by vertical stacking. According to the low basicity of the amino group, only weak H-bonding is expected.

Notes: On the Biosynthesis of γ-Dodecanolactone in Ripening Fruits: Flavor Constituents from Strawberries (Fragaria ananassa) and Peaches (Prunus persica)Administration of deuterium-labelled 9,10-expoxy[8,8-2H2]heptadecanoic acid 8a/b and 9,10-dihydroxy-[8,8-2H2]methylheptadecanoate 9 as lower analogues of oleic acid 1 to ripening fruits of strawberries (Fragaria ananassa) and peaches (Prunus persica) results in the emission of labelled γ-undecanolactone (5) as the lower analog of γ-dodecanolactone (2). The transformation proceeds with loss of a single D-atom from C(8) of the precursors. Early precursors, like the C17-epoxy-acids 8a/b yield (4R)-γ-undecanolactone (5) of high enantiomeric purity, while later intermediates results in (4R)-γ-undecanolactone (5) of low purity. The data support a biosynthetic sequence involving the consecutive action of an epoxide hydrolase and β-oxidation to generate the correct chain length of the lactone percursor. The final steps proceed via cyclization of the 3,4-dihydroxyundecanoic acid 13 to the 3-hydroxy-γ-undecanolactone 14. Elimination of H2O and reduction of the intermediate γ-undec-2-enolactone 15 terminate the biosynthesis of 5. The sequence is representative for the biosynthesis of naturally occurring γ-dodecanolactone (2).

Notes: Derivatives of fully cross-conjugated tetraethynylethene (3,4-diethynylhex-3-ene-1,5-diyne) 1 are versatile precursors to multinanometer-sized molecular rods with all-C-backbones. Oxidative polymerization (CuCl, N,N,N′,N′-tetramethylethylenthylenediamine (TMEDA), O2) of the trans-bis-deprotected trans-bis(triisopropylsilyl)-protected tetraethynylethene 2 yielded, after end-capping with phenylacetylene, the remarkably stable, soluble oligomers 3-7 with a persilylethynylated poly(triacetylene) (PTA) backbone [—(C≡C—CR=CR—C≡C)n—] and a length of 19.4 (3), 26.8 (4), 34.3 (5), 41.8 (6), and 49.2 (7) Å (Scheme 1). These compounds underwent facile one-electron reductions with the number of reversible reduction steps being equal to the number of tetraethynylethene moieties in each molecular rod. Oxidative Eglinton-Glaser homo-coupling of tetraethynylethenes 8-10 with a single free ethynyl group provided the fully silyl-protected 3,4,9,10-tetraethynyl-substituted dodeca-3,9-diene-1,5,7,11-tetraynes 11-13 (Scheme 2) and, after alkyne deprotection, the novel hydrocarbon 14, a C20H6 isomer, and its partially silyl-protected derivative 15. Oxidative hetero-coupling between two different tetraethynylethene derivatives, one with a single and the other with two free terminal ethynyl groups, yielded the extended chromophores 16-21 composed of 3 or 4 tetraethynylethene moieties (Scheme 3). The linearly conjugated oligomers 16 and 17 with the PTA backbone are isomeric to 19 and 20, respectively, which are members of the cross-conjugated expanded dendralenes, i.e., dendralenes with butadiynediyl fragments inserted between each pair of double bonds [—(C≡C—C(=CR2)—C≡C)n—]. The electronic absorption spectra of these compounds were compared and analyzed in terms of the competition between linear and cross-conjugation in determining the extent of π-electron delocalization. Although steric factors on π-electron conjugation remain to be clarified, this analysis strongly suggests that cross-conjugation is not an efficient mechanism for π-electron delocalization. All extended acetylenic-olefinic chromophores considered in this study exhibited remarkably high stability and did not decompose when exposed to laboratory air and light for months. In agreement with this observation, electrochemical studies demonstrated that the compounds are difficult to oxidize with the oxidation potentials in THF (0.1M(Bu4N)PF6) being higher than 1.0 V (vs. the ferrocene/ferrocenium couple).

Notes: Optically Active 3-Amino-2H-azirines as Synthons for Enantiomerically Pure αα-Disubstituted α-Amino Acids: Synthesis of the α-Methylphenylalanine Synthons and Some Model PeptidesThe synthesis of a novel 2-benzyl-2-methyl-3-amino-2H-azirine derivative with a chiral amino group is described. Chromatographic separation of the diastereoisomer mixture yielded the pure diastereoisomers 9a and 9b (Scheme 4) which are the D- and L-2-methylphenylalanine ((α-Me)Phe) synthons, respectively. The reaction of 9a and 9b with thiobenzoic acid and with Z-leucine yielded the monothiodiamides 10a and 10b (Scheme 5) and the dipeptide derivatives 11a and 11b (Scheme 6), respectively. Methanolysis of 11b yielded 12b. The absolute configuration of 10a was established by X-ray crystallography. The absolute configuration of (α-Me)Phe in 12b has been deduced from the known configuration of L-leucine.

Notes: Upon heating in AcOH, the stereoisomeric (Z)- and (R)-6,9-dioxocyclodex-3-enyl derivatives, 5 and 6, respectively, obtained by HgO/I2 oxidation of 5-hydroxy-8-oxo-8,14-seco-5α-androstane-3β,17β-diyl diacetate (3), undergo an unusual intramolecular rearrangement to give the corresponding unsaturated (5R,9R)- and (5R,9S)-spiro-lactones 7 and 8, respectively. Hydroxylation of the C=C bond in 7 and 8, and subsequent glycol cleavage of the resulting diols 9 and 10 afforded the epimeric spiro-lactones (5R,9S)-11 and (5R,9R)-14, respectively, and in both cases, the ring-D-containing fragments 12 and 13.

Notes: The N′-(glycofuranosylidene)toluene-4-sulfonohydrazides 5 and 10 (Scheme 1) were prepared in good yields by oxidation (1,3-dibromo-5,5-dimethylhydantoin/Et3N) of the N′-glycosyltoluene-4-sulfonohydrazides 4 and 9, which were obtained from 2,3,5-tri-O-benzyl-D-ribose (3) and 2,3,5-tri-O-benzyl-D-arabinose (8), respectively, and toluene-4-sulfonohydrazide. The analogous naphthalene-2-sulfonohydrazides 7 and 12 were similarly prepared from 3 and 8 via 6 and 11. Photolysis in the presence of phenol of the sodium salt 15 (Scheme 2), best generated in situ, yielded the anomeric glycosides 16, some 5, and traces of the glycosides (1R)/(1S)-17. Photolysis of 15 in THF gave the sulfones α-D/β-D-18. Photolysis of 15 (quartz filter) and dimethyl fumarate led to a single cyclopropane 19, the sulfones α-D/β-D-18, and the N-(ribofuranosyl)-N′-(ribofuranosylidene)toluene-4-sulfonohydrazide 20. Similarly, N-phenylmaleimide afforded the cyclopropanes 21 and 22. Photolysis of the sodium salt of 10 and phenol afforded the anomeric glycosides α-D/β-D-23, the C-glycoside 24, and the sulfone 25. Photolytic glycosidation of 15 with N6-benzyladenine gave the two nucleosides 26 and 27 (Scheme 3).

Notes: First Example of an H-Shift in ‘Thiocarbonyl Aminides’ (N-(Alkylidenesulfonio)aminides)Reaction of benzyl azide (15a) with the sterically hindered C=S group of 4,4-dimethyl-1,3-thiazole-5(4H)-thiones 14 (Scheme 3) and 1,1,3,3-tetramethylindane-2-thione (17, Scheme 4) at 80° leads to the corresponding imines in high yield, without formation of any by-product. In contrast, 15a and 2,2,4,4-tetramethyl-3-thioxocyclobutanone (7) under the same conditions yielded, in addition to imine 19, products 20a and 21 (Scheme 5). For the formation of 20a, a reaction mechanism via [1,4]-H shift in the intermediate ‘thiocarbonyl aminides’ 23 is proposed (Scheme 6). Product 21 as well as the dithiazole derivative 22, which is formed only in the reaction with 4-nitrobenzyl azide (15c), are formal adducts of the dipole 23. Whereas precedents are known for the formation of cycloadducts of type 22, the pathway to 21 is not known. Two possible mechanisms of its formation are proposed in Schemes 8 and 9.

Notes: Synthetic attempts towards fully conjugated polymers 9 with pentafulvene-diyl structural units are described. Cationic polymerization of pentafulvenes 1a (R = X = Me) and 1b (R = X = MeS) nearly quantitatively gives polymers 8a and 8b with typical Mn and Mw values of 38800 and 53750, respectively, for 8a, and 12000 and 35900, respectively, for 8b. Key step of the conversion 8a → 9a (Scheme 6) is a quantitative bromination 8a → 32a, the structure of 32a being confirmed by analytical data as well as by spectroscopic comparison with model compound 23. Best results in view of two-fold the HBr elimination 32a → 9a are obtained with Et3N, but so far elimination has not been complete. Synthetic sequences are optimized with model compound 21 (Scheme 4). Here again, bromination 21 → 23 is quantitative, while two-fold HBr elimination 23 → 22 with Et3N proceeds in 51% yield. Dibromide 23 easily undergoes HBr elimination followed by a Br shift to give bromide 29. Contrary to cationic polymerization, anionic polymerization of simple pentafulvenes 1 to 2 (which would be attractive in view of the conjugated polymers 3) is not successful: For pentafulvene 1b (R = X = MeS), the main reaction is Diels-Alder-type dimerization 1b → 15b (Scheme 2), even under anionic conditions.

Notes: Copper(II)-Chloride Catalyzed ‘Carbene Dimerization’ of 1-Halogeno-1-lithiocyclopropanes: A Simple Access to Bi(cyclopropylidenes)A series of 13 bi(cyclopropylidenes) 11 are prepared in a simple one-pot reaction by halogeno-lithio exchange between 1,1-dibromocyclopropanes 1a-n and BuLi, in most cases at -95°, to give 1-bromo-1-lithiocyclopropanes 2a-n, followed by treatment with CuCl2 at low temperature and a simple workup at room temperature (Scheme 3c and Table 1). The yields of bi(cyclopropylidenes) 11 strongly depend on reaction parameters, as explicitly shown for the conversion 1f →→ 11f (Tables 2-8). Mixed couplings between two different carbenoids are possible (Scheme 4), while diastereoselectivity of the active transition-metal complex seems to be low. The structures of bi(cyclopropylidenes) 11 are confirmed by spectroscopic data as well as by X-ray analysis of an isolated crystalline diastereoisomer of 11k (Fig. 1).

Notes: Several compounds, structurally related to the insect-growth regulator Fenoxycarb (1), were designed and synthesized. These compounds were tested as growth inhibitors of Trypanosoma cruzi cells (epimastigotes). Compounds 6, 16, 18, and 22 were very active against T. cruzi making them promising good candidates either for blood-bank sterilization of Chagas'-disease surveillance, while compounds 11, 12, 13, and 19 showed a moderate degree of activity.

Notes: The reactions of azetidin-3-ones 6-10, readily available from the amino acids L-alanine, L-phenylalanine, L-valine, L-lysine, and L-aspartic acid, via the corresponding diazo ketones, with nucleophilic reagents such as complex hydrides, Grignard compounds, an ester enolate, and a Wittig ylide give the expected products 11-19 in good yields and mostly in high diastereoselectivities. New amino-alcohol, γ-amino- and γ-amino-β-hydroxy-carboxylic-acid derivatives of known configurations are thus available.

Notes: Irradiation (λ 〉 390 nm) of 2H-1-benzothiopyran-2-one (1) in the solid state affords selectively 6aα,6bα,12bα,12cα -tetrahydrocyclobuta[1,2-c:4,3-c′]bis[1]benzothiopyran -6,7-dione (2), the head-to-head (HH) cis-cisoid-cis-dimer, while irradiation of 1 in the solid state using shorter wavelengths (λ 〉 340 nm) affords a mixture of all four cis-fused tricyclic dimers 2-5. These results represent a novel wavelength effect in solid-state photochemistry.

Notes: The synthesis of 7-chloro-, 7-bromo-, and 7-iodo-substituted 7-deaza-2′-deoxyguanosine derivatives 2b-d is described. The regioselective 7-halogenation with N-halogenosuccinimides was accomplished using 7-[2-deoxy-3,5-O-di(2-methylpropanoyl)-β-D-erythro- pentofuranosyl]-2-(formylamino)-4-methoxy-7H-pyrrolo[2,3-d]- pyrimidine (4) as the common precursor. A one-pot reaction (2N aq. NaOH) of the halogenated intermediates 5a-c furnished the desired compounds. Also the 7-hexynyl derivative 2e of 7-deaza-2′-deoxyguanosine is described.

Notes: The 5-methyl(15N2)[O2,O4-17O2]uridine (= (15N2)[O2,O4-17O 2]ribosylthymine; 15) was synthesized and analyzed by 15N- and 17O-NMR spectroscopy. (15N2)Urea was condensed with 2,3-dibromo-2-methylpropanoyl chloride (3) and cyclized to form (15N2)thymine (5). After glycosidation, the 17O isotopes were introduced in two separate steps: hydrolytic ring opening of 2,5′-anhydro derivative 9 and hydrolysis of 3-nitro-1H-1,2,4-triazole derivative 12 with labelled water in the presence of a strong base. The 15N- and 17O-NMR spectra (Fig.) of 15 in phosphate-buffered water serve as references for heteronuclear NMR spectra of labelled RNA fragments.

Notes: Hetero-Diels-Alder cycloaddition of acylnitroso dienophile 4 with the N-(butadienyl)pyrrolidinone derivatives 2a, b led with complete regioselectivity to the oxazine adducts 5a, b (Scheme 1). Sequential osmylation, protection of the ensuing glycol, and reduction of the N—O bond gave the expected hemiaminals 11a, b which were characterized by their crystalline sulfite adducts 12a, b (Schemes 1 and 2). Deprotection and saponification of the latter led to aminodeoxyerythrose and to aminodeoxyribose derivatives as an equilibrium of pyrrolidinose equivalents, i.e., hemiaminals 14a, b, imines 14′a, b, and dimers 14″a,b, respectively (Scheme 3). Hydrocyanic acid addition to 11a, b led ultimately to the proline derivatives 16a, b (Scheme 2). Compound 11b proved to be an inhibitor of syncytium formation in AIDS-infected cells.

Notes: The thermal properties of two ferrocene derivatives, substituted by either one or two cholesteryloxycarbonyl units, were investigated. While the monosubstituted ferrocene derivative 1 was found to be non-mesomorphic, the disubstituted ferrocene derivative 2 exhibited a crystal smectic-B phase. This result shows that ferrocene-containing thermotropic liquid crystals, despite the bulkiness of the metallocene core, are not limited to disordered calamitic phases.

Notes: NaSMe in toluene leads to regioselective de-C-silylation of the bis[(trimethylsilyl)ethynyl]saccharide 2, but to decomposition of butadiynes such as 1 or 12. We have, therefore, combined the known reagent-controlled, regioselective desilylation of 2 and of 12 (AgNO2/KCN) with a substrate-controlled regioselective de-C-silylation, based on C-silyl groups of different size. This combination was studied with the fully protected 3 which was mono-desilylated to 4 or to 5 (Scheme 1). Triethylsilylation of 5 (→ 6) was followed by removal of the Me3Si group (→ 7), introduction of a (t-Bu)Me2Si group (→ 8) and removal of the Et3Si group yielded 9; these high-yielding transformations proceed with a high degree of selectivity. Iodination of 4 gave 10. The latter was coupled with 5 to the homodimer 11 and the heterodimer 12, which was desilylated to 13. The second building block for the tetramer was obtained by coupling 14 (from 7) with 5, leading to 15 and 16. Removal of the Me3Si group (→ 17) and iodination led to 18 which was coupled with 13 to the homotetramer 20 and the heterotetramer 19 (Scheme 2). Deprotection of 19 gave 21, which was, on the one hand, iodinated to 22, and, on the other hand, protected by the (t-Bu)Me2Si group (→ 23). Removal of the Et3Si group (→ 24) and coupling afforded the homooctamer 26 and the heterooctamer 25. Yields of iodination, silylation, and desilylation were consistently high, while heterocoupling proceeded in only 50-55%. Cleavage of the (i-Pr)3SiC and MeOCH2O groups of 11 (→ 27), 15 (→ 28), 20 (→ 29) and 26 (→ 30) proceeded in high yields (Scheme 3). Complete deprotection in two steps of the heterocoupling products 16 (→ 31 → 32), 19 (→ 33 → 34), and 25 (→ 35 → 36) gave the unprotected dimer 32, tetramer 34, and octamer 36 in high yields (Scheme 4). Only the dimer 32 is soluble in H2O; the 1H-NMR spectra of 32, 34, and 36 in (D6)DMSO (relatively low concentration) show no signs of association.

Notes: A two-step synthesis of 4-methylcolchicine (13), starting from colchicine (2), has been developed (Scheme 5). In three steps, 4-ethylcolchicine (28) is also accessible from 2 (Scheme 8). Colchicine (2) and its derivatives 13 and 28 have been transformed into the benzo[a]heptalene derivatives 9, 18, and 34, respectively, by Hofmann degradation of the corresponding deacetylcolchiceine 3, 19, and 29, respectively, followed by methylation of the two O-functions first with diazomethane and then with trimethoxonium tetrafluoroborate (Scheme 2 and 6). The thus formed tropylium salts gave, on deprotonation with Me3N in CHCl3, the expected pentamethoxybenzo[a]heptalenes 9, 18, and 34, respectively. X-Ray crystal-structure analysis of 9 (Fig.3) and 18 (Fig. 7), determination of the vicinal coupling constants of the H-atoms at the heptalene skeleton as well as the measurement of the racemization rate of the new benzo[a]heptalenes revealed a marked influence of the substituent at C(4) on the degree of twisting of the heptalene skeleton. The absolute configuration of the resolved heptalenes was deduced from their long-wavelength CD maxima around 350 nm. The heptalenes with a negative maximum in this range possess (7aP)-configuration.

Notes: The Reaction of 1-Halogeno-1-lithiocyclopropanes with CuCl2: Competition between ‘Carbene Dimerization’ and Oxidative CouplingThe 1-chloro-1-lithiocyclopropanes 2a-d react at low temperature with CuCl2 to give diastereoisomeric mixtures of oxidative-coupling products 5a-d and of ‘carbene dimers’ 6a-d. The relative amount of 5a-d increases with CuCl2 concentration and reaction time. Diastereoselectivity of the reaction seems to be low, and separation as well as spectroscopic structure assignment of single diastereoselectivity of the reaction seems to be low, and separation as well as spectroscopic structure assignment of single diastereoisomers are difficult. The conformational behavior of 1,1′-dichloro-1,1′-bi(cyclopropyls) 5c and 5d is discussed. Contrary to 2a-d, 1-bromo-1-lithiocyclopropanes normally react with CuCl2 to give ‘carbene dimers’ 6 and no coupling products 5. So far the only exception is 1-bromo-1-lithio-2-phenylcyclopropane 2e which in the presence of CuCl2 gives some percents of coupling products 5e besides carbene dimers 6b as main products. An X-ray structure analysis of the predominant diastereoisomer 5e was performed.

Notes: In contrast to organic reactions, which can almost always be described in terms of a single multiplicity, in organometallic systems, quite often more than one state may be involved. The phenomenon of two states of different multiplicities that determine the minimum-energy pathway of a reaction is classified as two-state reactivity (TSR). As an example, the ion/molecule reactions of ‘bare’ transition-metal-monoxide cations with dihydrogen and hydrocarbons have been analyzed in terms of the corresponding potential-energy hypersurfaces. It turns out that, besides classical factors, such as the barrier heights, the spin-orbit coupling factor is essential, since curve crossing between the high- and low-spin states constitutes a distinct mechanistic step along the reaction coordinates. Thus, TSR may evolve as a new paradigm for describing the chemistry of coordinatively unsaturated transition-metal complexes. This concept may contribute to the understanding of organometallic chemistry in general and for the development of oxidation catalysts in particular.

Notes: Funicolides A-C (1-3), D (5), and E (7) and 7-epifunicolide A (4), new 5,8(17)-diunsaturated briarane diterpenes, as well as the known analogue brianthein W (6), were isolated from the pennatulacean coral Funiculina quadrangularis (PALLAS, 1766) collected in the Tuscan archipelago. Easy degradation under oxidative and/or basic conditions served to assign the ester groups at C(2) or C(14), while revealing bis-allylic reactivity at C(7) with formation of 16-nortaxane derivatives.

Notes: 4-Amino-1,5-dihydro-2H-pyrrol-2-ones from Boron Trifluoride Catalyzed Reactions of 3-Amino-2H-azirines with Carboxylic Acid DerivativesReaction of 3-amino-2H-azirines 1 with ethyl 2-nitroacetate (6a) in refluxing MeCN affords 4-amino-1,5-dihydro-2H-pyrrol-2-ones 7 and 3,6-diamino-2,5-dihydropyrazines 8, the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH-acidic compound by C—C bond formation via C-nucleophilic attack of deprotonated 6a onto the amidinium-C-atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2-substituted 2-nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF3 catalysis to give 4-amino-1,5-dihydro-2H-pyrrol-2-ones 12 in 50-80% yield (Scheme 3, Table 2). In an analogous reaction, 3-amino-2H-pyrrole 13 is formed from 1c and the Li-enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF3 catalysis is proposed in Scheme 6.

Notes: In connection with the proposed structure of a trans-membrane cellular ion channel consisting of a complex between poly[(R)-3-hydroxy butanoate] (P(3-HB)) and calcium polyphosphate, CaPPi (ca. 150 units each), which is supposed to contain s-cis-bonds or even more highly strained ester conformations, we have prepared and studied the properties of the cyclic dimer of 3-HB, the diolide 1. All possible forms of 1, the rac-, the meso-, and the enantiomerically pure (R,R)- and (S,S)-compounds were prepared, purified, and characterized. The synthesis (Scheme 1) started from dimethyl succinate with the key step being the Baeyer-Villiger oxidation of the rac- and meso-2,5-dimethylcyclohexane-1,4-diones 5. The rac-diolide 1 was resolved by preparative chromatography on a Chiralcel OD column (Fig.1). The crystal structures of rac- 1 (Fig.3) and of meso- 1 (Fig.5) were determined by X-ray diffraction: the diolides 1 contain s-cis-ester bonds and an ester group with a conformation half way to the transition state of rotation (Fig.2). Strain energies for the diolides 1 of up to 17.8 kcal/mol are suggested. Accordingly, these compounds show reactivities similar to those of carboxylic-acid anhydrides or even acid chlorides. They cannot be chromatographed on silica gel, and they react with primary, secondary, and tertiary alcohols, and with amines to form derivatives of open chain 3-HB ‘dimers’, hydroxy acids 6, esters 7, and amides 8 (Scheme 2). The rate of acid-catalyzed ring opening of the diolides 1 with alcohols has been measured (Fig.6 and 7). From the results described, we conclude that it is unlikely for strained and reactive ester conformations to occur as part of ion channels through phospholipid bilayers of cells.

Notes: An efficient combination of electrospray mass spectrometry (ES-MS), spectrophotometric and 1H-NMR titrations in solution is used to characterize the assembly of the segmental ligand 2-{6-[1-(3,5-dimethoxybenzyl)-1H-benzimidazol-2-yl]pyridin-2-yl}-1, 1′-dimethyl-5,5′-methylene-2′-(5-methylpyridin-2-yl)bis[1H- benzimidazole] (L2) with ZnII and 4f metal ions, LnIII. Ligand L2 reacts with Zn(ClO4)2 in MeCN to give successively [Zn(L2)2]2+, where the metal ion is coordinated by the tridentate binding units of the ligands, and the double-helical head-to-head complex [Zn2(L2)2]4+. When L2 reacts with Ln(ClO4)3 (Ln = La, Eu, Lu), LaIII only leads to a well-defined cylindrical C1-symmetrical homodinuclear head-to-tail complex [La2(L2)3]6+ in solution, while chemical-exchange processes prevent the 1H-NMR characterization of [Eu2(L2)3]6+, and LuIII gives complicated mixtures of complexes. However, stoichiometric amounts of LnIII (Ln = La, Ce, Pr, Nd, Sm, Eu, Tb, Y, Lu), ZnII, and L2 in a 1:1:3 ratio lead to the selective formation of the C3-symmetrical heterodinuclear complexes [LnZn(L2)3]5+ under thermodynamic control. Detailed NOE studies show that the ligands are wrapped about the C3 axis defined by the metal ions, and the separation of dipolar and contact contributions to the 1H-NMR paramagnetic shifts of the axial complexes [LnZn(L2)3]5+ (Ln = Ce, Pr, Nd, Sm, Eu) in MeCN establishes that ZnII occupies the pseudo-octahedral capping coordination site defined by the three bidentate binding units, while LnIII lies in the resulting ‘facial’ pseudo-tricapped trigonal prismatic site produced by the three remaining tridentate units. Photophysical measurements show that [LnZn(L2)3]5+ (Ln = Eu, Tb) are only weakly luminescent because of quenching processes associated with the C3-cylindrical structure of the complexes. The use of 3d metal ions to control and design isomerically pure ‘facial’ tricapped trigonal prismatic lanthanide building blocks is discussed together with the calculation of a new nephelauxetic parameter associated with heterocyclic N-atoms coordinated to LnIII.

Notes: Reaction of the tartrate-derived diol (R,R)-α,α,α′,α′-tetraphenyl-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (TADDOL) with chlorodiphenylphosphane gives a new bis(diphenylphosphanyl) ligand (TADDOP). The complex 4 formed with PdCl2 has been crystallized and its structure determined by X-ray diffraction (Fig.1). The complex is used for Pd-catalyzed enantioselective 1,3-diphenylallylations of various nucleophiles which give products with enantiomer ratios of up to 88:12 (Scheme 2). Crystallization procedures lead to the enantiomerically pure (〉 99:1) product 11 derived from dimethyl malonate. The structure of the TADDOP complex 4 is compared with those of other transition-metal complexes containing chelating bis(diphenylphosphanyl) ligands (Fig.2). A crystallographic data base search reveals that the structures of transition-metal complexes containing two Ph2P groups (superpositions in Fig.3) fall into one of two categories: one with approximate C2 symmetry and the other with C1 symmetry (20 and 19 examples, resp.). A mechanistic model is proposed which correlates the conformational chirality (δ or λ) of the four Ph groups' arrangement in such complexes with the topicity of nucleophile approach on Pd-bound trans,trans-1,3-diphenylallyl groups (Scheme 3 and Table).

Notes: The regioselectivity of multiple cyclopropanations of C70 with 2-bromopropanedioates in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base (Bingel reaction) was investigated in a systematic study. Bisadduct formation occurred preferentially at the 6—6 bonds formed by the most pyramidalized sp2-C-atoms at the two opposite poles of the fullerene and, in the reaction with achiral bis[(ethoxycarbonyl)methyl]2-bromopropanedioate (13a), yielded three constitutionally isomeric bis(methano)fullerenes (Scheme 2). Two of them, C2-symmetrical (±)-1 and (±)-2, are chiral; a fact which had not been considered in previous investigations. Formation of the third, C2v-symmetrical isomer 3 was observed for the first time. Configurational descriptions for fullerene derivatives which possess a chiral chromophore as a result of specific functionalization patterns are proposed. Cyclopropanations of C70 with optically active bis[(S)-1-phenylbutyl] 2-bromopropanedioate (13b) yielded five optically active, C2-symmetrical bis-adducts 7-11 which could be separated by preparative HPLC and fully characterized (Scheme 3, Fig.4). Compounds 7/8 and 9/10 represent two constitutionally isomeric pairs of diastereoisomers, and their circular dichroism (CD) spectra show pronounced Cotton effects mainly due to strong chiroptical contributions from the chirally functionalized fullerene chromophores (Fig.7). Since the addition patterns on the fullerene surface in each pair of diastereoisomers have an enantiomeric relationship, their CD spectra closely resemble those expected for two enantiomers. In the third constitutional isomer 11, the addition pattern on the fullerene surface is C2v-symmetrical, and optical activity only results from the chiral addends. Its CD spectrum shows weak Cotton effects mainly from induced circular dichroism originating from the perturbation of the achiral fullerene chromophore by the attached chiral addends. Addition of diethyl 2-bromopropanedioate (2 equiv.) to the C2-symmetrical racemic bis-adduct (±)-2 yielded a mixture of tris-adducts and one major, C2-symmetrical tetrakis-adduct (±)-4 which was isolated in pure form (Scheme 4). Starting from the achiral C2v-symmetrical bis-adduct 3, one single Cs-symmetrical tris-(5) and one C2v-symmetrical tetrakis-adduct (6) were obtained as major products which were isolated and fully characterized (Scheme 5). The regioselectivity for introduction of a second addend in the same hemisphere of C70 is high and resembles the preferred pattern of bis-addition seen in the functionalization of C60.

Notes: It is shown that strains of the marine ciliate Euplotes raikovi are subtly variable in their production of secondary metabolites. Strains GA8 and 39W from Mediterranean and SB8 from Californian coasts produce the sesquiterpenoid epiraikovenal (3), while strains GA8 and SB8 also produce secoepiraikovenal (4), which play an instrumental niche-exploitation role and have also taxonomic significance. Comparison of 3 and 4 with raikovenal (2) and its putative biogenetic precursor 1, which have similar roles in the conspecific strain Morl from Casablanca coast in the Atlantic Ocean, inspired us the first case of intramolecular tele-dienone-olefin [2+2] photocycloaddition, exemplified here by the transformation of 1 into ent-3. This served also to unequivocally clarify the stereochemical relationship between 3 and 2.

Notes: The 5′-amino-5′-deoxy-2′,3′-O-isopropylideneadenosine (4) was obtained in pure form from 2′,3′-O-isopropylideneadenosine (1), without isolation of intermediates 2 and 3. The 2-(4-nitrophenyl)ethoxycarbonyl group was used for protection of the NH2 functions of 4 (→7). The selective introduction of the palmitoyl (= hexadecanoyl) group into the 5′-N-position of 4 was achieved by its treatment with palmitoyl chloride in MeCN in the presence of Et3N (→5). The 3′-O-silyl derivatives 11 and 14 were isolated by column chromatography after treatment of the 2′,3′-O-deprotected compounds 8 and 9, respectively, with (tert-butyl)dimethylsilyl chloride and 1H-imidazole in pyridine. The corresponding phosphoramidites 16 and 17 were synthesized from nucleosides 11 and 14, respectively, and (cyanoethoxy)bis(diisopropylamino)phosphane in CH2Cl2. The trimeric (2′-5′)-linked adenylates 25 and 26 having the 5′-amino-5′-deoxyadenosine and 5′-deoxy-5′-(palmitoylamino)adenosine residue, respectively, at the 5′-end were prepared by the phosphoramidite method. Similarly, the corresponding 5′-amino derivatives 27 and 28 carrying the 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus, were obtained. The newly synthesized compounds were characterized by physical means. The synthesized trimers 25-28 were 3-, 15-, 25-, and 34-fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the trimer (2′-5′)ApApA.

Notes: The 1′,2′-unsaturated 2′,3′-secoadenosine and 2′,3′-secouridine analogues were synthesized by the regioselective elimination of the corresponding 2′,3′-ditosylates, 2 and 18, respectively, under basic conditions. The observed regioselectivity may be explained by the higher acidity and, hence, preferential elimination of the anomeric H-C(1′) in comparison to H—C(4′). The retained (tol-4-yl)sulfonyloxy group at C(3′) of 3 allowed the preparation of the 3′-azido, 3′-chloro, and 3′-hydroxy derivatives 5-7 by nucleophilic substitution. ZnBr2 in dry CH2Cl2 was found to be successful in the removal (85%) of the trityl group without any cleavage of the acid-sensitive, ketene-derived N,O-ketal function. In the uridine series, base-promoted regioselective elimination (→19), nucleophilic displacement of the tosyl group by azide (→20), and debenzylation of the protected N(3)-imide function gave 1′,2′-unsaturated 5′-O-trityl-3′-azido-secouridine derivative 21. The same compound was also obtained by the elimination performed on 2,2′-anhydro-3′-azido-3′-azido-3′-deoxy-5′-O-2′,3′-secouridine (22) that reacted with KO(t-Bu) under opening of the oxazole ring and double-bond formation at C(1′).

Notes: An eight-step synthetic sequence led from the known D-xylo-pentodialdose 8 to imidazo-L-xylo-piperidinose 15, the key steps being the build-up of imidazole compound 12 by a van Leusen methodology and the intramolecular SN2 ring closure of the O-triflated benzylidene derivative 13. xylo-Piperidinose 15 appears in a half-chair conformation like the oxocarbonium ions which are the postulated intermediates in the glycoprocessing of the pyranose polysaccharides. This bicyclic azasugar should be a glycosidase inhibitor.

Notes: In 10 steps, 3′,4′-diethynyl-2′,3′,5′-trideoxy-5′-noruridine (14) was synthesized in 5% overall yield from commercial uridine, using conventional methods of nucleoside chemistry. As two functional groups capable to react with each other are present in the same molecule, the synthetic compound is able to form polymers, similar to the polynucleotides, by an acetylene coupling reaction.

Notes: The synthesis of spiropyrans 11 and 12 and spirooxazines 13-17 containing a thiophene moiety is described. Two different synthetic approaches were used. The spectrokinetic properties of these new compounds are reported.

Notes: A conformational analysis of the (3′S,5′R)-2′-deoxy-3′,5′-ethano-α-D-ribonucleosides (a-D-bicyclodeoxynucleosides) based on the X-ray analysis of N4-benzoyl-α-D-(bicyclodeoxycytidine) 6 and on 1H-NMR analysis of the α-D-bicyclodeoxynucleoside derivatives 1-7 reveals a rigid sugar structure with the furanose units in the l′-exo/2′-endo conformation and the secondary OH groups on the carbocyclic ring in the pseudoequatorial orientation. Oligonucleotides consisting of α-D-bicyclothymidine and α-D-bicyclodeoxyadenosine were successfully synthesized from the corresponding nucleosides by phosphoramidite methodology on a DNA synthesizer. An evaluation of their pairing properties with complementary natural RNA and DNA by means of UV/melting curves and CD spectroscopy show the following characteristics: i) α-bcd(A10) and α-bcd(T10) (α = short form of α-D)efficiently form complexes with complementary natural DNA and RNA. The stability of these hybrids is comparable or slightly lower as those with natural β-d(A10) or β-d(T10)( β = short form ofβ-D). ii) The strand orientation in α-bicyclo-DNA/β-DNA duplexes is parallel as was deduced from UV/melting curves of decamers with nonsymmetric base sequences. iii) CD Spectroscopy shows significant structural differences between α-bicyclo-DNA/β-DNA duplexes compared to α-DNA/β-DNA duplexes. Furthermore, α-bicyclo-DNA is ca. 100-fold more resistant to the enzyme snake-venom phosphodiesterase with respect to β-DNA and about equally resistant as α-DNA.

Notes: Two new enantioselective syntheses of the naphthopyranquinone antibiotic frenolicin B (1), of its enantiomer 2, and of its diastereoisomers 3 and 4 were accomplished using two different routes from optically active β-Hydroxy esters (R)- and (S)-11 and 18. β-Hydroxy esters (R)- and (S)-11 were prepared stereoselectively from optically active sulfenylacetates (S)- and (R)-10, respectively (Scheme 2, Method A). Alternatively, compound 18 was obtained in excellent yield by enantioselective hydrogenation of the corresponding β-keto ester 17, using a chiral ruthenium-complex catalyst (Scheme 3, Method B). Subsequently, compounds (S)-11 and 18 were transformed into frenolicin B (1). In analogy, Stereoisomers 2-4 were prepared from (S)- and (R)-11 in good yields.

Notes: The 2′-deoxyisoguanosine phosphonates 3a and 4a and the phosphoramidites 3b and 4b were prepared as building blocks for solid-phase oligonucleotide synthesis. The diphenylcarbamoyl (dpc) residue was introduced as 2-oxo protecting group which stabilizes the N-glycosylic bond against hydrolysis and prevents the molecule from side reactions. The dpc-protected building blocks 4a, b were employed in solid-phase synthesis and were found to be much more efficient than the unprotected compounds 3a, b. Oligonucleotides with alternating (11) or consecutive isoguanine residues (13-15) were synthesized. They form duplexes with parallel chain orientation. The aggregate d(T4-iG4-T4) (15) containing four consecutive 2′-deoxyisoguanosine is shown to be a tetramer similar to that of d(T4-G4-T4).

Notes: Khusimone (1), one of the main odor-donating compounds of vetiver oil is subject of the following study on structure/odor relationship. The omittance of the ethano bridge of the tricyclic khusimone leads to a bicyclic system. The stereoselective approach to this degraded structure is described, and the olfactory properties are studied. The key step of the synthesis of the hydrindane nucleus is based on a highly diastereoselective conjugate addition to a chiral oxo-cyclopentene-2-carboxylate.

Notes: The (2-dansylethoxy)carbonyl (= {2-{[5-(dimethylamino)naphthalen-l-yl]sulfonyl}ethoxy}carbonyl; dnseoc) group was employed for protection of the amino functions of the aglycone residues. The lactam function of 2′-deoxyguanosine was on the one hand unprotected and on the other hand alkylated at O6 of the aglycone with the 2-(4-nitrophenyl)ethyl (npe) and 2-(phenylsulfonyl)ethyl (pse) group, respectively. The syntheses of monomeric building blocks, both phosphoramidites and nucleoside- functionalized supports, are described for the three common 2′-deoxynucleosides (2′-deoxycytidine, 2′-deoxyadenosine, 2′-deoxyguanosine). As kinetic studies with the tritylated nucleosides showed, the dnseoc group is more labile towards DBU cleavage than the corresponding 2-(4-nitrophenyl)ethyl-(npe) and [2-(4-nitrophenyl)ethoxy]carbonyl(npeoc)-protected analogues (see Table 2). These results were confirmed by the very fast deprotection rate of the dnseoc groups at some oligonucleotides.

Notes: The absolute configuration of 3-methylpyrrolidine alkaloids isolated from the poison gland of ants Leptothoracini was determined as (3R). The enantiomeric separation by chiral gas chromatography and unambiguous structural assignment of the target compounds are described.

Notes: The synthesis of π-substituted heptalenecarboxylates or -dicarboxylates, starting with the easily available dimethyl 9-isopropyl-1, 6-dimethylheptalene-4, 5-dicarboxylate (2b), are described. Treatment of 2b with t-BuOK and C2Cl6 at -78° leads to the chemoselective introduction of a Cl substituent in Me-C(1) (see 5b in Scheme 1). Formation of the corresponding triphenylphosphonium salt 7b via the iodide 6b (Scheme 2) allowed a Wittig reaction with cinnamaldehyde in the two-phase system CH2Cl2/2N NaOH. Transformation of the 4, 5-dicar-boxylate of 2b into the corresponding pseudo-ester 10b allowed the selective reduction of the carbonyl function at C(4) with DIBAH to yield the corresponding 4-carbaldehyde 11b (Scheme 3). Wittig reaction of 11b with (benzyl) triphenylphosphonium bromide led to the introduction of the 4-phenylbuta-1, 3-dienyl substituent at C(4). The combination of both Wittig reactions led to the synthesis of the 1, 4-bis(4-phenylbuta-1, 3-dienyl)-substituted heptalene-5-carboxylate (all-E)-17b (Scheme 5). In a similar manner, by applying a Horner-Wadsworth-Emmons reaction, followed by the Wittig reaction, the donor-acceptor substituted heptalene-5-carboxylate (E;E)-22b was synthesized (Scheme7). Most of these new heptalenes are in solution, at room temperature, in thermal equilibrium with their double-bond shifted (DBS) isomers. In the case of (all-E)-17b and (E;E)-22b, irradiation of the thermal equilibrium mixture with light of λ -(439 ± 10) nm led to a strong preponderance ( 〉 90%) of the DBS isomers 17a and (E;E)-22a, respectively (Schemes 6 and 7). Heating of the photo-mixtures at 40° re-established quickly the thermal equilibrium mixtures. Heptalenes-carboxylates (all-E)-17a and (E;E)-22a which represent the off-state of a 1,4-conjugative switch (CS) system show typical heptalene UV/VIS spectra with a bathochromically shifted heptalene band III and comparably weak heptalene bands II and I which appear only as shoulders (Figs. 4 and 5). In contrast, the DBS isomers (all-E)-17b and (all-E)-22b, equivalent to the on-state of a 1,4-CS system, exhibit extremely intense heptalene bands I and, possibly, II which appear as a broad absorption band at 440 and 445 nm, respectively, thus indicating that the CSs (all-E)-17a⇌(all-E)-17b and (E;E)-22a⇌(E;E)-22b are perfectly working.

Notes: Configurational and Conformational Isomeric Antiaromatic [28]Tetraoxaporphyrinoids(4.2.4.2) and Aromatic [26]Tetraoxaporphyrin(4.2.4.2) Dications. A New Type of Molecular Dynamics in Macrocyclic SystemsThe [28]tetraoxaporphyrinoids(4.2.4.2) 6 are synthesized by cyclizing Wittig reaction of (E, E)-5, 5′-(buta-1, 3-diene-1, 4-diyl)bis[furan-2-carbaldehyde] (8) with (E, E)-{(buta-1, 3-diene-diyl)bis[(furan-5, 2-diyl)methylene]}bis-[triphenylphosphonium] dibromide (9) and 3, 3′-{[(E)-ethene-1, 2-diyl]bis(furan-5, 2-diyl)}bis[(E)-prop-2-enal] (22) with (E)-{(ethene-1, 2-diyl)bis[(furan-5.2- diy)methylene]}bis[triphenylphosphonium] dibromide (23). An alternative path to get 6 is the McMurry condensation of 8. Four different configurational isomers of 6 could be isolated and characterized by 1H-NMR spectroscopy. The (Z, EE, Z, EE)-isomer 6a is the first macrocyclic system where the inner and outer protons of the (E, E)-dienediyl bridges exchange by rotation around the adjacent single bonds. In the (Z, EE, E, EE)-isomer 6b, the (E)-ethenediyl bridge is rotationally active, while in the (E, ZE, E, EZ)-isomer 6c and in the (E, EZ, E, EZ)-isomer 6e, the rotation of both (E)-ethenediyl bridges is observed. When in the dynamic systems the rotation of the active (E)-double bonds at temperatures T 〈 -90° is frozen, all configurational isomers of 6 appear to be antiaromatic and paratropic. The oxidation of the [28]tetraoxaporphyrinoids 6c and 6e with DDQ yields the aromatic, diatropic [26]tetraoxaporphyrin(4.2.4.2) dications 21e/21e′ both with (E, EZ, E, EZ)-configuration but different fixed conformations. (Z, EE, Z, EE)-Isomer 6a is oxidized to give the (Z, EE, Z, EE)-dication 21a, while the oxidation of 6b yields a mixture of 21a and 21e/21e′. The standard formation enthalpies of the obtained and expected [28]tetraoxaporphyrinoids 6 and [26]tetraoxaporphyrin dications 21 have been calculated with the AM1 method, showing good accordance with the experimental results.

Notes: The synthesis of substituted cyclododeca-1,6-diallenes.( = cyclododeca-1,2,6,7-tetraenes) from cyclododeca-5,11-diyne-1,4-diols is described (Schemes 1 and 3). The ca. 1:1 mixtures of the stereoisomers of the cyclododeca-1,6-diallenes were formed in high yields from the ca. 1:1 diastereoisomer mixtures of the 1,4-disubstituted cyclododeca-5,11-diynes by reactions with Me2CuLi or t-BuMgCl/CuII. In mechanistically relevant experiments with the pure diastereoisomers of 1,4-dimethylcyclododeca-5,11-diyne-1,4-diol, it is demonstrated that the configuration is conserved in these reactions. The first synthesis of a 1-substituted cyclododeca-2,8-diyne bearing only one propargylic leaving group gives access to a mixed 12-membered allen-yne (Scheme 5).

Notes: This study was designed to unravel lipophilicity changes associated with the oxidation state of the S-atom in model compounds, drugs, and metabolites, special attention being given both to intermolecular and intramolecular effects. The methods used were experimental (potentiometry, CPC, and shake-flask techniques to measure lipophilicity, 13C-NMR spectroscopy to investigate tautomeric equilibria) and computational (quenched molecular dynamics and molecular lipophilicity potential). Simple, monofunctional model compounds were used to assess intermolecular forces, as revealed by the Δlog Poct-alk and Δlog Poct-chf parameters. Drugs and their metabolites proved to be good probes to study intramolecular effects in both neutral and anionic forms, as revealed by the difference between calculated and experimental log Poct values (the diff(log Pexp-calc) parameter). Sulindac and its metabolites showed a normal partitioning behavior, whereas the lipophilicity of sulfmpyrazone and its metabolites' was markedly affected by tautomeric and conformational equilibria.

Notes: The course of the thermocatalytic rearrangement of cycloprop-2-ene-1-carboxylates in the presence of dirhodium(II) tetrakis(perfluorobutyrate) ([Rh2(pfb)4]) was investigated by varying the substituents of the cyclopropene ring. Product composition is markedly influenced by the number, nature, and position of the substituents, which determine the regio- and stereoselectivity of the cyclopropene-ring cleavage. A mechanism is proposed in which attack of the electrophilic RhII species is concerted with disrotatory ring opening of the incipient cyclopropyl cation and affords a metal-complexed vinylcarbene. The chemoselectivity of the latter is consistent with that of other carbenes generated in the presence of [Rh2(pfb)4].

Notes: Under the co-operative influence of two prosthetic groups, and independent of the TiCl4 concentration, complete and constant diastereofacial π-selection was achieved during the [4 + 2] cycloaddition of cyclopentadiene to N,N′-fumaroyl-di[(2R)-bornane-10,2-sultam] ((-)-1c); reactive conformations are discussed.

Notes: The β-dienoate (+)-(5S)-13a (86% ee; meaning of α and β as in α- and β-irone, resp.) was obtained from (-)-(5S)-9a via acid-catalyzed dehydration of the diastereoisomer mixture of allylic tertiary alcohols (+)-(1S,5S)-15/(+)-(1R,5S)-15 (Scheme 3). Prolonged treatment gave clean isomerization via a [1,5]-H shift to the α-isomer (-)-(R)-16a with only slight racemization (76% ee; Scheme 4). In contrast, the SnCl4-catalyzed stereospecific cyclization of (+)-(Z)-6 to (-)-trans-8a (Scheme 2), followed by a diastereoselective epoxidation to (+)-11 gave, via acid-catalyzed dehydration of the intermediate allylic secondary alcohol (-)-12, the same ester (+)-13a (Scheme 3), but with poor optical purity (13% ee), due to an initial rapid [1,2]-H shift. The absolute configuration of (-)-16a-c was confirmed by chemical correlation with (-)-trans-19 (Scheme 4). 13C-NMR Assignments and absolute configurations of the intermediate esters, acids, aldehydes, and alcohols are presented.

Notes: The synthesis of (E)-hex-3-ene-l, 5-diynes and 3-methylidenepenta-1, 4-diynes with pendant methano[60]-fullerene moieties as precursors to C60-substituted poly(triacetylenes) (PTAs, Fig. 1) and expanded radialenes (Fig. 2) is described. The Bingel reaction of diethyl (E)-2, 3-dialkynylbut-2-ene-1, 4-diyl bis(2-bromopropane-dioates) 5 and 6 with two C60 molecules (Scheme 2) afforded the monomeric, silyl-protected PTA precursors 9 and 10 which, however, could not be effectively desilylated (Scheme 4). Also formed during the synthesis of 9 and 10, as well as during the reaction of C60 with thedesilylated analogue 16 (Scheme 5), were the macrocyclic products 11, 12, and 17, respectively, resulting from double Bingel addition to one C-sphere. Rigorous analysis revealed that this novel macrocyclization reaction proceeds with complete regio- and diastereoselectivity. The second approach to a suitable PTA monomer attempted N, N′-dicyclohexylcarbodiimide(DCC)-mediated esterification of (E)-2, 3-diethynylbut-2-ene-l, 4-diol (18, Scheme 6) with mono-esterified methanofullerene-dicarboxylic acid 23; however, this synthesis yielded only the corresponding decarboxylated methanofullerene-carboxylic ester 27 (Scheme 7). To prevent decarboxylation, a spacer was inserted between the reacting carboxylic-acid moiety and the methane C-atom in carboxymethyl ethyl 1, 2-methano[60]fullerene-61, 61-dicarboxylate (28, Scheme 8), and DCC-mediated esterification with diol 18 afforded PTA monomer 32 in good yield. The formation of a suitable monomeric precursor 38 to C60-substituted expanded radialenes was achieved in 5 steps starting from dihydroxyacetone (Schemes 9 and 10), with the final step consisting of the DCC-mediated esterification of 28 with 2-[1-ethynyl(prop-2-ynylidene)]propane-1, 3-diol (33). The first mixed C60-C70 fullerene derivative 49, consisting of two methano[60]fullerenes attached to a methano[70]fullerene, was also prepared and fully characterized (Scheme 13). The Cs-symmetrical hybrid compound was obtained by DCC-mediated esterification of bis[2-(2-hydroxy-ethoxy)ethyl] 1, 2-methano[70]fullerene-71, 71-dicarboxylate (46) with an excess of the C60-carboxylic acid 28. The presence of two different fullerenes in the same molecule was reflected by its UV/VIS spectrum, which displayed the characteristic absorption bands of both the C70 and C60 mono-adducts, but at the same time indicated no electronic interaction between the different fullerene moieties. Cyclic voltammetry showed two reversible reduction steps for 49, and comparison with the corresponding C70 and C60 mono-adducts 46 and 30 indicated that the three fullerenes in the composite fullerene compound behave as independent redox centers.

Notes: By the tether-directed remote functionalization method, a series of bis- to hexakis-adducts of C60, i.e., 1-7 (Fig. 1), had previously been prepared with high regioselectivity. An efficient method for the removal of the tether-reactive-group conjugate was now developed and its utility demonstrated in the regioselective synthesis of bis- to tetrakis(methano)fullerenes ( = di- to tetracyclopropafullerenes-C60-Ih) 9-11 starting from 4, 5, and 7, respectively (Schemes 2, 4, and 5). This versatile protocol consists of a 1O2 ene reaction with the two cyclohexene rings in the starting materials, reduction of the formed mixture of isomeric allylic hydroperoxides to the corresponding alcohols, acid-promoted elimination of H2O to cyclohexa-1,3-dienes, Diels-Alder addition of dimethyl acetylenedicarboxylate, retro-Diels-Alder addition, and, ultimately, transesterification. In the series 9-11, all methano moieties are attached along an equatorial belt of the fullerene. Starting from C2v-symmetrical tetrakis-adduct 15, transesterification with dodecan-1-ol or octan-1-ol yielded the octaesters 16 and 17, respectively, as noncrystalline fullerene derivatives (Scheme 3). The X-ray crystal structure of a CHCl3 solvate of 11 (Fig. 3) showed that the residual conjugated π-chromophore of the C-sphere is reduced to two tetrabenzopyracylene substructures connected by four biphenyl-type bonds (Fig. 5). In the eight six-membered rings surrounding the two pyracylene (= cyclopent[fg]acenaphthylene) moieties, 6-6 and 6-5 bond-length alteration (0.05 Å) was reduced by ca. 0.01 Å as compared to the free C60 skeleton (0.06 Å) (Fig. 4). The crystal packing (Fig. 6) revealed short contacts between Cl-atoms of the solvent molecule and sp2- and sp3-C-atoms of the C-sphere, as well as short contacts between Cl-atoms and O-atoms of the EtOOC groups attached to the methano moieties of 11. The physical properties and chemical reactivity of compounds 1-11 were comprehensively investigated as a function of degree and pattern of addition and the nature of the addends. Methods applied to this study were UV/VIS (Figs. 7-11), IR, and NMR spectroscopy (Table 2), cyclic (CV) and steady-state (SSV) voltammetry (Table 1), calculations of the energies of the lowest uunoccupied mmolecular orbitals (LUMOs) and electron affinities (Figs. 12 and 13), and evaluation of chemical reactivity in competition experiments. It was found that the properties of the fullerene derivatives were not only affected by the degree and pattern of addition but also, in a remarkable way, by the nature of the addends (methano vs. but-2-ene-1, 4-diyl) anellated to the C-sphere. Attachment of multiple thano moieties along an equatorial belt as in the series 8-11 induces only a small perturbation of the original fullerene π-chromophore. In general, with increasing attenuation of the conjugated fullerene π-chromophore, the optical (HOMO-LUMO) gap in the UV/VIS spectrum is shifted to higher energy, the number of reversible one-electron reductions decreases, and the first reduction potential becomes increasingly negative, the computed LUMO energy increases and the electron affinity decreases, and the reactivity of the fullerene towards nucleophiles and carbenes and as dienophile in cycloadditions decreases.

Notes: Crystal and solution structures of the enantiomerically pure and the racemic pairs of (η3-allyl) {2-[2′-(diphenylphosphino)phenyl]-4,5-dihydro-4-phenyloxazole}palladium(II) hexafluorophosphates (1, and rac-1, resp.) and tetraphenylborates (2, and rac-2, resp.) as well as (η3-allyl){2-[2′-(diphenylphosphino)phenyl]-4,5-dihydro-4-isopropyloxazole}palladium(II) tetraphenylborate (3) were characterized by X-ray crystallography and 1H-NMR spectroscopy. In the solid state, rac-1 and rac-2 proved to be disordered with both diastereoisomeric complexes in the crystal. The complexes 2 and 3 exist only in the ‘exo’ form. The X-ray structures show that the [PdII(η3-allyl)] moiety may adopt different configurations between a nearly symmetrical three-electron PdII(π3-allyl) system and an asymmetrical allyl group with a η1- and a η2-bonding to the metal center. The [PdII(η3-allyl)] system of rac-1 and of ‘endo’ rac-2 is closer to the former, and that of 2, ‘exo’-rac-2, and 3 closer to the later geometry. The 1H-NMR spectra of the hexafluorophosphates 1 and rac-1 show two sets of signals of the allylic protons in an ‘exo’/‘endo’ ratio of 2:3. The tetraphenylborates 2, rac-2, and 3 give only one set of broad signals of the allylic protons.

Notes: ‘Acetyleno-oligosaccharides’ in which two terminal ethynyl substituents enclose an angle (significantly) below 180° are building blocks for the preparation of cyclodextrin analogues. This is illustrated by the preparation of a cyclotrimer and a cyclotetramer; the C3-symmetrical cyclotrimer 18 (Scheme 1) was synthesized in 13 steps (7.7%) and the C4-symmetrical cyclotetramer 51 (Scheme 3) in 14 steps (4.3%) from the known dialkyne 21. The solubilities of 18 and 51 in H2O were determined by gravimetry; a saturated solution is 130 mM in the trimer 18 and 12.8 mM in the tetramer 51. The dependence of the optical rotation of 18 and 51 in H2O on the concentration, and the concentration dependence of the 1H-NMR chemical shift of the signals of the 1CH groups of 51 (D2O) suggest that there is no significant self-association of 18 and 51.

Notes: The chiral biyclic bis-lactams of structures 3 and 4 were synthesized from the key intermediate 2′b, the N,N′-bis(4-methoxybenzyl) derivative of 2 (X = MeO) (Scheme 6). The synthesis of this intermediate involved two key steps: (1) a double condensation of glyoxylic acid/anisamide (= oxoacetic acid/4-methoxybenzamide) adduct 11c with veratrole (1,2-dimethoxybenzene; 10) allowed the introduction of two glycine units at the 4,5-positions of the veratrole ring to give 18c (Schemes 3 and 4); (2) in order to circumvent the hydrolysis of 4-methoxybenzoyl protective groups which proved to be unfeasible, these groups were transformed into 4-methoxybenzyl groups through a sequence involving thiocarbonylation followed by reduction (Scheme 5). Thereafter, the double intramolecular cyclization of the resulting diamino diester 22c proceeded easily to afford 2′b. This intermediate may be transformed via the tetrol 2′g or the diol 2′h into the N-protected derivatives of 2 (X = OR) and of 3 (X = OCOR). Cleavage of the 4-alkuxybenzyl groups was achieved by ceric ammonium nitrate. However, when the aromatic ring bore ether functions (N-protected 2), this normal reaction was accompanied by the oxidative ring cleavage to give the diene-diester structure 4 (Schemes 5 and 6).

Notes: The kinetics of the Cu2+ complexation by macrocycles 1 (4-[(l,4,8,11-tetraazacyclotetradec-1-yl)methyl]-benzoic acid) and 2 (N-propyl-4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]-benzamide) as well as by macrocycle 1 conjugated to bovine serum albumin (bsa) and to ribonuclease A (rnase) were studied by stopped flow techniques. For 1 and 2, the kinetics were followed in the mM range monitoring the d-d* absorption band of the Cu2+ complex. From the pH dependence of kobs, the rate law is v = [Cu2+] (kLH[LH] + kLH2[LH2]), where kLH and kLK2 are the bimolecular rate constants for Cu2+ with the diprotonated (LH2) and monoprotonated (LH1) form of the ligand, respectively. The values are kLH2 = 1.7(1) M-1s-1 and kLH = 2.3(1) 105 M-1s-1 for 1, and kLH2, = 0.28(9) M-1s-1 and kLH = 2.0(1) 105 M-1s-1 for 2. The kinetics of the Cu2+ incorporation into 1,2 and 1 conjugated to bsa and rnase, i.e., 3 and 4, respectively, were also followed using nitroso-R salt as a metal indicator in the μM range, i.e., under conditions typical for the ‘post-labeling’ technique to give radiolabeled monoclonal antibodies. In these cases, the reaction takes place between the 1:1 complex of Cu2+ with nitroso-R-salt and the macrocycle. At pH 6.5, the rates are very similar to each other indicating that the complexation properties of the macrocycle attached to a protein are not very different from those of the free ligand under comparable conditions.

Notes: The synthesis of a variety of hydroxylactams from ω-phthalimidoalkanoates using a triplet-sensitized photodecarboxylation reaction initiated by intramolecular photo electron transfer is described. Ring sizes available by this method span from 4 (benzazepine-1,5-dione 7) to 26 (cyclodipeptide 26e). Ground-state template formation is proposed as the explanation for the high efficiency of this reaction and for the decrease in reactivity in the presence of organic bases instead of metal carbonates. The crucial step in this macrocyclization reaction seems to be the protonation of the intermediary ketyl radials (Scheme 4). Spacer groups investigated were alkyl chains (C3-C11: 5c-h, 11a, 12), ether (16, 18), ester (20, 22), and amide (26a-f) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products were observed, indicating the high preference for intra-vs. intermolecular photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (cf, products 11 and 12) in contrast to comparable singlet reactions. Except for the lactones 22, all products were stable under the photolysis conditions. Prolonged irradiation of 22 led to the formation of the spiro compounds 23, probably via an intermediary acyliminium betaine (Scheme 8). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glycine spacer (as in 27a and 27b), probably the consequence of a strong intramolecular H-bond (Scheme 10).

Notes: The Diels-Alder adduct of 2,4-dimethylfuran to 1-cyanovinyl (1′R)-camphanate ((+)-(1R,2S,4R)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′R)-camphanate ((+)-1)) was converted into (+)-2,7-dideoxy-2,4-di-C-methyl-L-glycero- ((+)-6) and -D-glycero-L-altro-heptono-1,4-lactone ((+)-7), into (-)-(3R,4R,5R,6S)-3,4:5,7-bis(isopropylidenedioxy)-4,6-dimethylheptan-2-one ((-)-22), and into (+)-(2R,3R,4R,5S,6S)-3,4:5,6-bis(isopropylidenedioxy)-2,4-dimethylheptanal ((+)-34). Condensation of ((+)-34 with the lithium enolate of (-)-(1R,4R,5S,6R)-6-exo-[(tert-butyl)dimethylsilyloxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.1] heptan-2-one ((-)-38; derived from (+)-1) gave a 3:2 mixture of aldols (+)-39 and (+)-40 (mismatched pairs of a α-methyl-substituted aldehyde and (E)-enolate) whereas the reaction of (±)-34 with (±)-38 gave a 10:1 mixture of aldols (±)-41 and (±)-39. A single aldol, (-)-44, was obtained to condensing (+)-34 with the lithium enolate of (+)-(1S,4S,5S,6S)-5-exo-(benzyloxy)-1,5-endo-dimethyl-7-oxabicyclo[2.2.1]heptan-2-one ((+)-43; derived from (-)-(1S,2R,4S)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′S)-camphanate ((-)-3)). All these cross-aldolisations are highly exo-face selective for the bicyclic ketones. The best stereochemical matching is obtained when the lithium enolates and α-methyl-substituted aldehydes can realize a ‘chelated transition state’ that obeys the Cram and Felkin-Anh models (steric effects). Polypropionate fragments containing eleven contiguous stereogenic centres and tertiary-alcohol moieties are thus prepared with high stereoselectivity in a convergent fashion. The chiral auxiliaries ((1R)- and (1S)-camphanic acid) are recovered at the beginning of the syntheses.

Notes: The Diels-Alder adduct (±)-3 of 2,4-dimethylfuran and 1-cyanovinyl acetate was converted stereoselectively into benzyl 6-(4-chlorophenylsulfonyl)-1,3-exo,5-trimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl (26) and -2-endo-yl ether (36). Addition of LiAlH4 to the latter led to the 3-O-benzyl derivatives 28 and 37 of (1RS,2SR,3SR,6SR)- and (1RS,2SR,3RS,6SR)-5-(4-chlorophenylsulfonyl)-2,4,6-trimethylcyclohex-4-ene-1,3-diol, respectively. Methylenation of 6-exo-(4-chlorophenylthio)-1-methyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-one (16), obtained by reaction of (±)-3 with 4-Cl-C6H4SCl and saponification gave, 6-exo-(4-chlorophenylthio)-1-methyl-3,5-dimethylidene-7-oxabicyclo [2.2.1]heptan-2-one (43), the reduction of which with K-Selectride afforded 6-exo-(4-chlorophenylthio)-1,3-endo-dimethyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-endo-ol (44). The 3-O-benzyl derivative 48 of (1RS,2RS,3RS,6SR)-5-(4-chlorophenylsulfonyl)- 2,4,6-trimethylcyclohex-4-ene-1,3-diol was derived from 44 via based-induced oxa-ring opening of benzyl 6-endo-(4-chlorophenylsulfonyl)-1,3-endo-5-endo-trimethyl-7-oxabicyclo[2.2.1]hept-2-endo-yl ether (49). Benzylation of 28, followed by reductive desulfonylation and oxidative cleavage of the cyclohexene moiety afforded (2RS,3SR,4RS,5RS)-3,5-bis(benzyloxy)-2,4-dimethyl-6-oxoheptanal (32).

Notes: A novel tricyclic dipeptide template, formally derived by coupling (2S,4S)-4-aminoproline (Pro(NH2)) and (S)-2-(carboxymethyl)proline (Pro(CH2COOH)) as a diketopiperazine, has been synthesized in a form suitable for solid-phase peptide synthesis using Fmoc chemistry. This template was incorporated into the cyclic molecule cyclo(-Ala1-Asn2-Pro3-Asn4-Ala5-Ala6-Temp-) (Temp = template), whose conformation in H2O was studied by NMR methods. Average solution structures derived by restrained simulated annealing point to a highly populated βI-turn within the Asn-Pro-Asn-Ala motif and also indicate which conformations are likely to be preferred by the template.

Notes: The syntheses of both diastereoisomers of 5′-ethyl-substituted thymidine dimers, the (5′R)- and (5′S)-configurated 33a and 33b respectively, in which the natural phosphodiester linkage is replaced by an amide group (C(3′)-CH2CONH-CH(5′)(Et)), arc described. Their fully protected derivatives 35a and 35b, respectively, are suitable for incorporation into antisense oligonucleotides. Unexpectedly, an attempted PdII-catalysed aza-Claisen rearrangement of trichloroacetimidate 7 provided the diastereoisomerically pure cyclopropane derivative 17, whose structure was confirmed by X-ray analysis.

Notes: New Pathways to Precursors of PentalenePentalene dimers 2 and 3 are easily available in moderate yields by CuCl2-induced oxidative coupling of dilithium-pentalenediide (5) (Scheme 1). On the other hand, NBS bromination of 1,5-dihydropentalene (4) or of 1,2-dihydropentalene (8) gives unstable 1-bromo-1,2-dihydropentalene (9), while subsequent in-situ elimination with Et3N exclusively gives syn-cis-pentalene dimer 2 in moderate yields (Scheme 3). NMR-Spectroscopic evidence for compounds 2, 3, and 9 is presented, and mechanistic alternatives for the formation of pentalene dimers 2 and 3 are discussed.

Notes: Four new iridoid glucosides 1-4, named blumeosides A-D, were isolated from the methanolic stem-bark extract of Fagraea blumei G. DON. (Loganiaceae). They were accompanied by the benzyl-alcohol derivative di-O-methylcrenatin (5) and the flavone C-glucoside swertisin (6). The structures of 1-4 were established by spectroscopic methods, including FAB-MS, and 1H- and 13C-NMR, and by alkaline hydrolysis. Blumeosides A (1) and C (3) are 10-O-(2,5-dihydroxytercphthalo) adoxosidic acid and 10-O-(2-hydroxyterephthalo)adoxosidic acid, respectively. In blumeosides B (4) and D (2), both carboxylic groups of the terephthalic-acid moiety are esterified by adoxosidic-acid units, Blumeosides A-D (1-4) inhibited bleaching of crocin induced by alkoxyl radicals. Blumeosides A (1) and D (2) also demonstrated scavenging properties towards the 2,2-diphenyl-1-picryl-hvdrazvl (CDPPH) radical in TLC autographic and spectrophotometric assays.

Notes: The kinetic model of column chromatography is revisited to explicitly show that this approach yields, when neglecting axial dispersion, a rather simple analytical expression depending only on two dimensionless parameters, namely a dimensionless kinetic retention parameter and a dimensionless time parameter. An expression for the time corresponding to the maximum of the peak is also proposed.

Notes: The αv/β3 integrin is implicated in human tumor metastasis and angiogenesis. It has been shown that structures of the sequence cyclo(-Arg1-Gly2-Asp3-D-Phe4-Xaa5-) (I) and cyclo(-Arg1-Gly2-Asp3-Phe4-D-Xaa5-) (II) bind with high affinity and the latter with high selectivity to this receptor. The residues Xaa and D-Xaa accept a broad variety of amino acids. Here, we report on the synthesis, activities, and conformational analysis of cyclic Arg-Gly-Asp (RGD) peptides containing liophilic amino acids Xaa or D-Xaa in position 5. For I, these were (2S)-2-aminohexadecanoic acid (Ahd) and N′-hexadecylglycine (Hd-Gly) and in II, D-Ahd and Hd-Gly, and, for control purposes, Ahd were incorporated (Fig. 1). The enantiomerically pure a-amino acids were obtained by non-enantioselective synthesis and subsequent enzymatic separation of isomers using acylase I (Scheme). Hd-Gly was prepared in a modified procedure according to Stewart from ethyl bromoacetate and hexadecylamine (Scheme). The synthesis and physicochemical properties of the corresponding (9H-fluoren-9-ylmethoxy)carbonyl (Fmoc) derivatives, compatible with solid-phase peptide synthesis, are described. Structure elucidation by NMR reveals that the lipid modification has no significant impact on the template structures when incorporated into them. For peptides I with Xaa = Ahd or Hd-Gly (1 or 2), a βII′/γ-turn-like arrangement with D-Phe in i+1 position of the β-turn is found. Peptides II with D-Xaa = D-Ahd or Hd-Gly (3 or 4) exhibit a βII′/γ-turn conformation with Gly in i+1 position of the β-turn, whereas II with Ahd instead of D-Xaa, i.e., lacking a D-amino acid in position 4 or 5 (5). adopts no defined conformation. However, in assays of receptor specificity employing human αvv/β3 integrin, the compounds exhibit IC50 values ranging from nanomolar to less than millimolar. These results indicate that although the arrangement of the pharmacophoric groups is preserved in the target compounds, the biological activity is highly dependent on spatial requirements of the lipid anchor in the receptor binding pocket. Obviously, only certain positions do not affect the binding.

Notes: The conformational analysis of naturally occurring cytostatic cyclic heptapeptides axinastatin 2, 3, and 4 was carried out by two-dimensional NMR spectroscopy in combination with distance-geometry (DG) and molecular-dynamics (MD) calculations in explicit solvents. The synthesized secondary metabolites were examined in (D6)DMSO. Axinastatin 2 was also investigated in CD3OH. In all structures, Pro2 is in the i + 1 position of a βI turn and Pro6 occupies the i + 2 position of a βVIa turn about the cis amide bond between residue 5 and Pro6. In all peptides, a bifurcated H-bond occurs between residue 4 CO and the amide protons of residue 1 and 7. For axinastatin 2 and 3, an Asn Ig turn was found about Asn1 and Pro2. We compared these structures with conformations of cyclic heptapeptides obtained by X-ray and NMR studies. A β-bulge motif with two β turns and one bifurcated H-bond is found as the dominating backbone conformation of cyclic all-L-heptapeptides. Axinastatin 2, 3, and 4 can be characterized by six trans and one cis amide bond resulting in a β/βVI(a)-turn motif, a conformation found for many cyclic heptapeptides. Detailed biological tests of the synthetic compounds in different human cancer cell lines indicates these axinastatins to be inactive or of low activity.

Notes: In the presence of activating agents, the N-acylglycine 8 reacts with electrophilic alkynes via the münchnone9 to the pyrrolopyridines (= indolizines) 10, 18, and 19 (Scheme 1 ), Depending on the nature of the activating agent and the reaction temperature, the formation of the pyrroles was accompanied by partial epimerization to the manna-configurated epimers 16 and 17. The gluco-configurated pyrrolopyridine 10 was deprotected to 12. Silylation of 12, followed by reduction and desilylation, gave the hexol 15. Cycloaddition of 9 to 4-toluenesulfonyl cyanide yielded 53% of the imidazole 23, while cycloaddition to phenyl cyanate gave the phenoxyimidazole 28 in low yields only (Scheme 2). As expected, the deprotected pyrroles 12, 15, 20, and 21 are weak inhibitors of retaining β-glucosidases, while the deprotected imidazole 24 derived from 23 proved a good inhibitor of sweet-almond β-glucosidases and a powerful inhibitor of Caldocellum saccharolyticum β-glucosidase.

Notes: Tetrahydrobenzo[a]pyrrolizidines (= octahydro-1H-pyrrolo[2,1-a]isoindoles) and tetrahydrobenzo[a]indo-lizidines, (= decahydropyrido[2,1-a]isoindoles) were prepared stereoselectively in four steps through an amineinduced ring-opening of 3-bromo-2,5-dimethylthiophene 1,1-dioxide (1) with L-prolinol (9), piperidine-2-methanol (10), and piperidine-2-ethanol (11), yielding the dienes (2S)-1-[(2E,4Z)-4-bromohexa-2,4-dienyl]pyrrolidine-2-methanol (12), 1-[(2E,4Z)-4-bromohexa-2,4-dienyl]piperidine-2-methanol (13), and 1-[(2E,4Z)-4-bromo-hexa-2,4-dienyl]piperidine-2-ethanol (14; Scheme2), which, after conversion into their α,β-unsaturated esters, cyclized in a TiCl4-catalyzed intramolecular Diets-Alder reaction (Scheme3). A discussion on the mechanism of the ring opening reaction including semiempirical and ab initio calculations is also presented.

Notes: The X-ray crystal-structure analyses of two N-enoyl-toluenesultam derivatives 1 are reported. The structural differences with their bornanesultam analogues 2 as well as stereochemical aspects with respect to their [4 + 2] and [3 + 2] cycloadditions are discussed.

Notes: A series of tetra-N-alkylated 1,4,8,11-tetraazacyclotetradecanes have been synthesized and their complexation potential towards Ni2+ and Cu2+ studied. In the case of sterically demanding alkyl substituents, such as i-Pr, PhCH2, or 2-MeC6H4CH2, no metal complexes are formed, whereas for substituents such as Me, Et, and Pr, the metal ion is incorporated into the macrocycle. The spectroscopic properties of the Ni2+ and Cu2+ complexes in aqueous solution indicate that, depending on the sterical hindrance of the N-substituents, the complexes are either square planar or pentacoordinated. All these Ni2+ and Cu2+ complexes react with N3- to give ternary species, the stability of which have been determined by spectrophotometric titrations. The tendency to bind N3- decreases with increasing steric hindrance of the alkyl substituents. The X-ray studies of the Ni2+ complex with the macrocycle 11, substituted by two Me and two Pr groups, and that of the Cu2+ complex with the tetraethyl derivative 8 show that in the solid state, the metal ions exhibit square planar coordination with a small distortion towards tetrahedral geometry.

Notes: The title compounds 6 and 7 have been prepared from the known 2,3-di-O-benzyl-4,6-O-benzylidene-D-galactose (18) and N2-acetyl-tri-O-benzyl-D-glucosamine oxime (29) in eight and six steps, respectively. The azidonitrile leading to the benzylated galacto-tetrazole 16 was prepared from 14 and cyclized under the conditions of its formation (Scheme 1). The alcohol 13 was obtained by oxidation of 10 followed by reduction. Better yields and diastereoselectivities were realized, when the benzylidene-protected D-galacto-alcohol 20 was subjected to oxido-reduction, yielding the L-altro-alcohol 22 via the ketone 21 (Scheme 2). Treatment of the corresponding tosylate 24 with NaN3 yielded the tetrazole 25, which was deprotected to 6. The tetrabenzyl ether 16 (from 14, or from 25 via 27) was reduced to 28 and deprotected to give the known deoxygalactostain 8 (Scheme 2). Oxidation of the hydroxynitrile 30, derived from 29, followed by reduction of 32 yielded mostly the L-ido-hydroxynitrile (Scheme 3), which was tosylated and treated with NaN3 to give the tetrazole 35a and its manno-isomer 36a, while Al(N3)3 yielded (E)- and (Z)-38 (Scheme 4). The intermediate azide 39 was isolated besides 40 when NH4N3/DMF was used; thermolysis of 39 gave mostly 35a, which was deprotected to 7, besides some elimination product 41. Both 6 and 7 are stable in the pH range 1-10; at pH 12, 6 is unaffected but, 7 shows some epimerization to the manno-configurated isomer 43. The tetrazole 6 is a competitive inhibitor of the β-galactosidases from E. coli (K1 = 1 μM, pH 6.8) and bovine liver (K1 = 0.8 μM, pH 7.0); the N-acetyl-β-D-glucosaminidase from bovine kidney is competitively inhibited by 7 (K1 ≊ 0.2 μM, pH 4.1).

Notes: (R)-and (S)-γ-cyclogeranic acid ((R)-and (S)-9, resp.) were obtained by resolution of the racemate, and their absolute configurations determined by chemical correlation. The γ-acids (R)-and (S)-9 were converted into (R)-and (S)-methyl γ-cyclogeranate ((R)-and (S)-6, resp.), and (R)-and (S)-γ-damascone ((R)-and (S)-5, resp.). A more direct entry to (R)-and (S)-9 consisted in the enantioselective protonation of a thiol ester enolate with (-)- or (γ)-N-isopropylephedrine((-)- or (γ)-20) and subsequent hydrolysis of the (R)-and (S)-S-phenyl γ-thiocyclogeranate ((R)- and (S)-24, resp.; 97% ee). The esters (R)- and (S)-24 were also used as precursors of (R)- and (S)-γ-damascone ((R)- and (S)-5, resp.). Alternatively, (S)-5 (75% ee) was obtained by enantioselective protonation of ketone enolate 29 with (-)-N-isopropylephedrine ((-)-20). Organoleptic evaluation demonstrated that the (S)-enantiomers of methyl γ-cyclogeranate and γ-damascone are markedly superior to their (R)-enantiomers.

Notes: The microscopic ionization behavior of piroxicam was investigated using two different approaches, i.e., direct UV spectroscopy and an indirect analogue approach (deductive method). The best microscopic pKa values (pKa12 = 4.60, pKa21 = 5.40, pKa22 = 2.72, and pKa11 = 1.92) were obtained by the deductive method using as pKa22 the pKa of the enolic O-methylated piroxicam 2. The results show remarkable electrostatic effects in the protonation/deprotonation equilibria, a marked increase in the acidity of the enolic function (2.68 pKa units) being caused by the pyridinium group. The electronic structure of piroxicam was studied based on 1H-NMR chemical shifts at various ionization states, indicating an extended electron conjugation through the molecule. The partition measurements in octan-1-ol/H2O of zwitterionic compound 3 (the pyridyl N-methyl derivative of piroxicam (1)) suggest that the two opposite charges in zwitterionic piroxicam are indeed in a close intramolecular proximity.

Notes: The synthesis of the trisaccharide β-D-Galp-(1→3)-β-D-GalpNAc-(1→3)-α-D-Galp-1-OPr (2) and of the tetrasaccharide α-L-Fucp-(1→2)-β-D-GalpNAc-(1→3)-β-D-Galp-1-OPr (3), starting from the disaccharidic dihydrooxazole donor 5, is described. Glycosylation of 5 with 6 in the presence of Me3SiOTf gave the trisaccharide 7 which was deprotected with standard methods to give, via 8, compound 2 (Scheme 1). Alternatively, protection of 8 as the 4′,6′-O-benzylidene derivative 9 followed by glycosylation with 10 and by standard deprotection afforded the tetrasaccharide 3 (Scheme 2). Biological testing showed that trisaccharide 2 is unable to inhibit the binding of the monoclonal antibody MBr1 to the target tumor cells MCF7, while tetrasaccharide 3 inhibits the binding in ca. 7-fold extent with respect to the previously tested trisaccharide α-L-Fucp-(1→2)-β-D-Galp-(1→3)-β-D-GalpNAc-1-OPr. These results indicate that the galactose corresponding to the unit D of compound 1 plays an important role in defining the MBr1-recognized epitope and confirm the essential role of fucose for MAb recognition.

Notes: Boophiline (1), a new sterol amide was isolated from the cattle tick Boophilus microplus (Ixodidae). The structure was assigned as N-[3-(sulfooxy)-25ξcholest-5-en-26-oyl]-L-isoleucine by detailed 2D NMR investigations in conjunction with FAB mass spectrometry and acidic hydrolyses. Complete assignment of the diastereotopic methylene protons of the ring system could be deduced from the NMR data. In agar dilution assays, 1 exhibited antifungal properties against Cladosporium cucumerinum and antibacterial activity against Bacillus subtilis and Escherichia coli.

Notes: The classical rules for Cope rearrangements predict a transition state with chair form to be favored over the boat form. On the other hand, bridged homotropylidenes, which allow only a boat-form transition state by steric reasons, have extremely low barriers. A controversy about the correct pathway and the different possible intermediates and transition states of the reaction has gone on for years. In this work, the hypersurfaces of barbaralane, in comparison with the boat- and chair-form of hexa-1,5-diene, are computed by the ab inito CASSCF (6,6)/6-31G** method starting with UMP2/6-31G** natural orbitals (NO's). All three hypersurfaces show characteristic features, and, moreover differ from each other. A hitherto undiscussed intermediate, bicyclo[2.2.0]hexane, was localized on the boat-hexa-1,5-diene pathway. So it is noteworthy that our transition state for the boat-hexa-1,5-diene does not correspond to the transition states found by other authors for this conformation. The computed enthalpies of activation of boat- and chair-hexa-1,5-diene, and barbaralane are in good agreement with the experimental data.

Notes: As one of the regulatory gene products in the HIV-1 genome, Rev protein must be translocated from the nucleus to the cytoplasm to exert its function. Therefore, inhibition of Rev protein translocation could be a useful target for HIV therapy. An extract from the Streptomyces strain A92-308902 with very potent inhibitory activity was found in the course of a high throughput screening with a Rev translocation assay (RTA). Bioassay-guided fractionation with gel filtration, normal-phase and reversed-phase chromatography yielded six RTA-active metabolites belonging to the leptomycin family, the known leptomycin A (1), leptomycin B (2), kazusamycin B (3), and kazusamycin A (4). and the hitherto unknown dilactonmycin (5) and delactonmycin (6), together with an inactive cyclic hexadepsipeptide L-156,620 (7). The structures were established mainly by spectroscopic methods (UV, FT-IR, FAB-MS, 1H-NMR, 13C-NMR(JMOD), DQ-COSY, ROESY, HSQC, and HMBC). The configuration of all C=C bonds of 1-6 was unambiguously established by analysis of coupling constants and ROESY spectra. All isolated leptomycins 1-6 inhibit Rev translocation at nanomolar concentrations. Six derivatives (2a-c and 4a-c) of leptomycin B (2) and kazusamycin A (4) were also prepared and tested in the RTA for preliminary investigations on structure-activity relationships.

Notes: The olefins mentioned in the title were copolymerized with CO in the presence of palladium catalysts modified with dicyclohexyl{(R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl}phosphine. Productivities up to 95 g/(gPd · h) were achieved. The obtained copolymers were recovered in the pure, regio- und stereoregular polyketone structures3. The isotactic poly[2-benzyl-1-oxopropane-1,3-diyl] (3a) and its analogues 3b, c were found to isomerize to the corresponding spirocyclic poly[3-(arylmethyl)tetrahydrofuran-2,2-5,5-tetrayl-2-oxy-2-methylene]s 4 in a suspension in CHC13, thus indicating that the spiroketal structure is thermodynamically the most stable for these copolymers. However, the atactic material did not undergo any structural transformation. These results show that regularity at the centers of chirality in the main chain is a prerequisite for the conversion of the polyketone to the spiroketal structure.

Notes: Two pairs of enantiomerically pure cis-fused cyclopenteno-1,2,4-trioxanes (7, ent-7 and 8, ent-8) are prepared (Schemes 1-3). Their identities are established by dye-sensitized photo-oxygenation of ent-7 and 8, ent-8 to the allylichydroperxides, reduction to the corresponding alcohols, and conversion to the (1S)-camphanates (Scheme 4), the structures of which are determined by X-ray analysis. The dynamic properties of ent-7 are investigated by NMR spectroscopy and PM3 calculations. Evidence for an easily accessible twist-boat conformation is obtained. The in vitro and in vivo antimalarial activities of 7, ent-7,8, and ent-8 as well as those of the racemic mixtures are evaluated against Plasmodium falciparum, P. berghei, and P. yoelii. No correlation is observed between configuration and activity. Racemates and pure enantiomers have commensurate activities. The mode of action on the intraerythrocytic parasite is rationalized in terms of close docking by the twist-boat conformer of the trioxane on the surface of a molecule of heme, single-electron transfer to the O—O σ* orbital, and scission to the acetal radical which then irreversibly isomerizes to a C-centered radical, the ultimate lethal agent (Scheme 5).

Notes: Methyl 2-acetyl-3-{[2-(dimethylamino)-1-(methoxycarbonyl)ethenyl]amino}prop-2-enoate (4) and phenyl-methyl 2-acetyl-3-{[2-(dimethylamino)-1(methoxycarbonyl)ethenyl]amino}prop-2-enoate (5) were prepared in three steps from the corresponding acetoacetic esters, and used as reagents for the preparation of N3-protected 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 10-12, 5H-thiazolo[3,2-a]pyrimidin-5-one 13, 4H-pyrido[1,2-a]-pyridin-4-one 19 and 2H-1-benzopyran-2-ones 20-23. Free 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 24-26 were prepared from 10-12 by removal of the 2-(methoxycarbonyl)-3-oxobut-1-enyl or 3-oxo-2-[(phenyl-methoxy)carbonyl]but-1-envl as N-protecting group by various methods.

Notes: Cyclophanes 3 and 4 were prepared as initiator cores for the construction of dendrophanes (dendritic cydophanes) 1 and 2, respectively, which mimic recognition sites buried in globular proteins. The tetra-oxy[6.1.6.1]paracyclophane 3 was prepared by a short three-step route (Scheme 1) and possesses a cavity binding site shaped by two diphenylmethane units suitable for the inclusion of flat aromatic substrates such as benzene and naphthalene derivatives as was shown by 1H-NMR binding titrations in basic D2O phosphate buffer (Table 1). The larger cyclophane 4, shaped by two wider naphthyl(phenyl)methane spacers, was prepared in a longer, ten-step synthesis (Scheme 2) which included as a key intermediate the tetrabromocyclophane 5. 1H-NMR Binding studies in basic borate buffer in D2O/CD3OD demonstrated that 4 is an efficient steroid receptor. In a series of steroids (Table 1), complexation strength decreased with increasing substrate polarity and increasing number of polar substituents; in addition, electrostatic repulsion between carboxylate residues of host and guest also affected the binding affinity strongly. The conformationally flexible tetrabromocyclophane 5 displayed a pronounced tendency to form solid-state inclusion compounds of defined stoichiometry, which were analyzed by X-ray crystallography (Fig. 2). 1,2-Dichloroethane formed a cavity inclusion complex 5a with 1:1 stoichiometry, while in the 1:3 inclusion compound 5b with benzene, one guest is fully buried in the macrocyclic cavity and two others are positioned in channels between the Cyclophanes in the crystal lattice. In the 1:2 inclusion compound 5c, two toluene molecules penetrate with their aromatic rings the macrocyclic cavity from opposite sides in an antiparallel fashion. On the other hand, p-xylene (= 1,4-dimethylbenzene) in the 1:1 compound 5d is sandwiched between the cyclophane molecules with its two Me groups penetrating the cavities of the two macrocycles. In the 1:2 inclusion compound 5e with tetralin (= 1,2,3,4-tetrahydronaphthalene), both host and guest are statically disordered. The shape of the macrocycle in 5a-e depends strongly on the nature of the guest (Fig. 4). Characteristic for these compounds is the pronounced tendency of 5 to undergo regular stacking and to form channels for guest inclusion; these channels can infinitely extend across the macrocyclic cavities (Fig. 6) or in the crystal lattice between neighboring cyclophane stacks (Fig. 5). Also, the crystal lattice of 5c displays a remarkable zig-zag pattern of short Br…O contacts between neighboring macrocycles (Fig. 7).

Notes: An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L-phenylalanine cyclohexylamide (2) as chiral auxiliary. The free amino acids 1a, b were converted to the Nα-Boc,Nγ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b, and 9b, the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b, whereas 8a crystallized in an extended backbone conformation.

Notes: The absolute configuration of a series of naturally occurring and semi-synthetic halogenated furanones is proposed on the basis of chemical interconversions and X-ray and CD analyses. The CD analyses clearly reveal that the presence of the allylic O-atom has a strong influence in determining the sign and intensity of the low energy π→π* transition.

Notes: Benz[a]azulene (1) is synthesized in five steps (cf. Scheme 2) starting from commercially available 2-iodobenzyl alcohol (4) and tropylium tetrafluoroborate in an overall yield of 44%. The key step (cf. also Scheme 1) is the intramolecular Heck reaction of the 8-phenylsulfonyl-substituted heptafulvene 7, which leads in nearly quantitative yield directly to 10-(phenylsulfonyl)benz[a]azulene (8). The desulfonylation of 8 can be accomplished by Julia's method with Na2S2O4/NaHCO3 in DMF/H2O at 85-90°, thus leading to pure 1 in 78% yield. The phenylation of 8 with PhLi or PhCul at -78° in THF occurs regioselectively at C(9). Dehydrogenation of the formed dihydroazulenes with o-chloroanil in toluene at room temperature gives 9-phenyl-10-(phenylsulfonyl)-benz[a]azulene (9) in 70% yield (cf. Scheme 3), which, again, can be desulfonylated with Na2S2O4/NaHCO3 in DMF/H2O in good yields. The addition of PhLi to 1 in THF occurs at temperatures ≥ -25°. Ionic dehydrogenation (1. Ph3C+BF4-/MeCN; 2. Et3N) of the dihydro forms leads to 3, as the main product, and its positional isomers.

Notes: Dialkynes of the type 3 (Scheme 1) are regioselectively deprotected by treating them either with base in a protic solvent (→4), or- after exposing the OH group- by catalytic amounts of base in an aprotic solvent (→5 and 8). The Me3Si-protected 12 (Scheme 2) is inert to catalytic BuLi/THF which transformed 11 into 9, while K2CO3/MeOH transformed both 10 into 9, and 12 into 13, evidencing the requirement for a more hindered (hydroxypropyl)silyl substituent. C-Silylation of the carbanions derived from 17-19 (Scheme 3) with 15 led to 20-22, but only 22 was obtained in reasonable yields. The key intermediate 27 was, therefore, prepared by a retro-Brook rearrangement of 23, made by silylating the hydroxysulfide 16 with 15. The OH group of 27 was protected to yield the {[dimethyl(oxy)propyl]dimethylsilyl}acetylenes (DOPSA's) 21, 28, and 29. The orthogonally protected acetylenes 20-22, 28, and 29 were de-trimethylsilylated to the new monoprotected acetylene synthons 30-34. The scope of the orthogonal protection was checked by regioselective deprotection of the dialkynes 39-42 (Scheme 4), prepared by alkylation of 35 (→39), or by Pd0/CuI-catalyzed cross-coupling with 36-38 (→40-42). The cross-coupling depended upon the solvent and proceeded best in N,N,N′,N′ -teramethylethylenediamine (TMEDA). Main by-product was the dimer 43. On the one hand, K2CO3/MeOH removed the Me3Si group and transformed 39-42 into the monoprotected 44-47; catalytic BuLi/THF, on the other hand, transformed the alcohols 48-51, obtained by hydrolysis of 39-42, into the monoprotected dialkynes 52-55, all steps proceeding in high yields. Addition of the protected DOPSA groups to the lactones 56 (→57-59) and 62 (→63) (Schemes 5 and 6) gave the corresponding hemiketals. Reductive dehydroxylation of 57 and 58 failed; but similar treatment of 59 yielded the alcohol 61. Similarly, 63 was transformed into 64 which was protected as the tetrahydropyranyl (Thp) ether 65. In an optimized procedure, 62 was treated sequentially with lithiated 31, BuLi, and Me3SiCl (→66), followed by desilyloxylation to yield 60% of 67, which was protected as the Thp ether 68. Under basic, protic conditions, 68 yielded the monoprotected bisacetylene 69; under basic, aprotic conditions, 67 led to the monoprotected bisacetylene 70. These procedures are compatible with the butadiynediyl function. The butadiyne 73 was prepared by cross-coupling the alkyne 69 and the iodoalkyne 71 (obtained from 70, together with the triiodide 72) and either transformed to the monosilylated 76 or, via 77, to the monosilylated 78. Formation of the homodimers 74 and 75 was greatly reduced by optimizing the conditions of cross-coupling of alkynes.

Notes: Photolysis and Ag-benzoate-catalyzed decomposition of the diazo ketones 2 and 4 derived from Z-Ala-OH and Z-Ala-Ala-OH in the presence of oligonucleotide derivatives bearing at the 5′-terminus an NH2 instead of the OH group, or an aminohexyl phosphate group lead to Z-protected 3-aminobutanoyl and to Z-Ala-β-HAla derivatives, respectively (conjugates 12, 13, and 17-23, Schemes 3-5), In solution, this amide-forming acylation reaction could be realized only with oligomers containing up to 8 unprotected nucleotide building blocks (Schemes 3 and 4). With the analogous polymer-bound and protected oligonucleotide derivatives as amino nucleophiles, excellent yields were obtained with all chain lengths tested (up to 15mer Scheme 5), The products were purified by reversed-phase HPLC and characterized by MALDI-TOF mass spectrometry (Figs. 2-4, Table 2) and by capillary gel electrophoresis (Fig.2).

Notes: We describe a versatile novel approach for the synthesis of 2, 4, 6-trisubstituted pyrimidines on solid support. Thus, polymer-boun J thiouronium salt 2 reacted in high yield in a cyclocondensation reaction with the acetylenic ketones 3 to form, after tert-butyl-ester cleavage, the polymer-bound carboxylic acids 4, which were cleaved by oxidation with 3-chloroperbenzoic acid and pyrrolidine to form the 2-pyrrolidinylpyrimidine-4-carboxylic acids 6a-c in high yields and purities without further purification (Scheme 1). Alternatively, acid 4a was subjected to an Ugi four-component condensation which gave the polymer-bound Ugi products 9a-e in good yields (Scheme 2). Multidirectional cleavage reaction of sulfone 8a with different nucleophiles resulted in the clean formation of pyrimidine-4-carboxamides 10-13 (Scheme 3). This strategy combines efficiently solid-phase chemistry with a multicomponent reaction and a multidirectional cleavage step to form highly diverse pyrimidines in a parallel array.

Notes: The title compounds 4 are obtained by photolysis of simple N-alkylpyridinium salts in H2O or alcohol. On reaction with [Fe2(CO)9] in THF, 4 gives bicyclic tricarbonyliron complexes 13a-d, which on oxidative decomplexation with ceric ammonium nitrate afford cis-fused cyclopenteno-β-lactams 15a-d.

Notes: The first crystal structure of a molybdenum complex 9 with a hydrogenated pterin and a sulfur ligand contributes to the discussion about the active center of molybdenum and tungsten enzymes containing a molybdopterin cofactor. Complex 9 was synthesized through a redox reaction of [MoVIO2 (LN-S2)] (8; LN-S2 = pyridine-2, 6-bis(methanethiolato)) with 5, 6, 7, 8-tetrahydropterin (7). 2 HCl (H4Ptr.2 HCl). The complex crystallizes, with a non-coordinating Cl-atom acting as a counterion, in the monoclinic space group C2/c (No. 15) with cell dimensions a = 22.900(5), b = 10.716(2), c = 17.551(4) Å, β = 120.36(3)°, and Z = 8. We interpret 9 as [MoIVO(LN-S2)(H+-q-H2Ptr)]Cl (q = quinonoid; H2Ptr = dihydropterin), i.e., a MoIV monooxo center coordinated by a pyridine-2, 6-bis(methanethiolato) ligand and a protonated dihydropterin. The spectroscopic properties of this new complex are comparable to those of other crystalline molybdenum complexes of hydrogenated pterins without additional S-coordination. The slightly H2O-soluble complex 9 reacts with the natural enzyme substrate DMSO very slowly, possibly due to the lack of easily dissociable ligands at the metal center.

Notes: The solid-state structures of three stereoisomer, 1-3, of the cyclic tetramer of 3-aminobutanoic acid are presented. These cyclo-β-peptides were found to be highly insoluble materials, and it proved to be impossible to grow crystals of sufficient quality for X-ray single-crystal analysis. The samples of 1-3 were, however, suitable candidates for structure determination from powder diffraction data (Fig. 1), and the application of this method is described. All three isomers have been found to adopt tubular structures (Figs. 2-4) in a fashion similar to those already observed for certain cyclo-α-peptides. The stacks of 16-membered rings are held together by four nonlinear C=O…H—N H-bonds between pairs of molecules (Fig.5).

Notes: β-Cryptoxanthin (1) was acetylated and then epoxidized with monoperoxyphthalic acid. After hydrolysis, repeated chromatography, and crystallization, (3S,5R,6S)-5,6-epoxy-β-cryptoxanthin (3), (3S,5S,6R)-5,6-epoxy-β-cryptoxanthin (4), (3R,5′R,6′R)-5′,6′-epoxy-β-cryptoxanthin (5), (3S,5R,6S,5′R,6′S)-5,6:5′,6′-diepoxy-β-cryp-toxanthin (6), and (3S,5S,6R,5′S,6′R)-5,6:5′,6′-diepoxy-β-cryptoxanthin (7) were isolated as main products and characterized by their UV/VIS, CD, 1H- and 13C-NMR, and mass spectra. The comparison of the carotenoid isolated from yellow, tomato-shaped paprika (Capsicum annuum var. lycopersiciforme flavum) with 3-5 strongly supports the structure of 3 for the natural product.

Notes: The 14-membered tetraazamacrocyclic Ni2+ and Cu2+ complexes of 4 (1, 4, 8-trimethyl-11-[(2-methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), 5. (1, 4-dimethyl-8, 11-bis[2-(methylthio)ethyl]-l, 4, 8, 11-tetraazacyclotetradecane), and 7 (1, 4, 8, ll-tetrakis[2-(methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), with pne, two, and four methylthio-substituted pendant chains, respectively, and the Ni2+ complex of 6 (1, 4-dimethyl-8, 11-bis (2-methoxyethyl)-1, 4, 8, 11-tetraazacyclotetradecane), with two methoxy-substituted pendant chains, were synthesized and their chemistry studied with regard to modelling F430. Solution spectra in H2O, MeCN, and DMF indicate participation of the side chain in metal coordination when the donor group is a thioether, whereas no coordination with the metal ion is observed with the ether group. Similarly the X-ray structures of the thioether-containing compounds [Ni(5)](ClO4)2, [Cu(5)](ClO4)2, and [Cu(7)](ClO4)2 show a coordination number of 5, whereas that of [Ni(6)](ClO4)2 with ether pendant chains, shows a coordination number of 4. Cyclic voltammetry of these complexes in MeCN reveals that Ni2+ is reversibly reduced to Ni+ between -0.64 and -0.77 V vs. SCE, the potential being influenced by the nature and number of the pendant chains. At more negative potentials, the thioether is cleaved, whereby a thiol is formed; the thiol is then oxidized at ca. + 0.8 V vs. SCE, when a glassy carbon electrode is used, or at ca. 0 V vs. SCE at a dropping Hg electrode. No cleavage of the ether bond in [Ni(6)](ClO4)2 is observed under similar conditions.

Notes: The photochemical synthesis of indole derivatives starting from the indoline-2-thiones 1 is described. Irradiation of indoline-2-thiones 1 in the presence of alkenes 3 gave 2-alkyl-3H-indoles 4-7 or 2-alkylindoles 8-22 through the ring cleavage of the intermediates, spirocyclic amino-thietanes, initially derived by [2 + 2] cycloaddition of the C=S bond of 1 and the C=C bond of 3. Irradiation of 1 in the presence of trialkylamines 26 gave desulfurization products 27-32 and unexpected 3-alkylindoles 33-40. N-Acylindoline-2-thiones 11-p yielded the deacylated products, indoline-2-thiones 1a-b, and ethyl esters 43 through γ-H abstraction by the excited thioamide S-atom when irradiated in CDC13/EtOH or benzene/EtOH. Oxygen analogues 2a-d also underwent intramolecular H abstraction to give the indolin-2-ones 2e-f and ethyl esters 43 in a similar way.