ALBERT

Notizen: The benzyl-protected glycosyl acetates 1, 6, 11, and 15 react with MeOPPh2 under catalysis by TMSOTf to yield diastereoselectively the glycosylphosphine oxides 2, 3, 8, 12, 13, and 16, with a strong preference for the 1,2-cis-configurated anomers. Hydrogenolysis of the major products gave the crystalline, unprotected phosphine oxides 4, 9, 14, and 17, of which 4 was transformed in to the acetate 5, and 9 into the benzoate 10. The benzylated phosphine oxides 4, 8, 12, and 16 were reduced with Cl3SiH in the presence of a tertiary amine to form the phosphines 18, 21, 24, and 26, which were transformed into the phosphine sulfides 19, 22, 25, and 27. Moreover, 18 and 21, were characterized as the borane adducts 20, and 23. The structure of the (arabinofuranosyl)phosphine oxide 12, the corresponding sulfide 25, and of the borane complex 20 were established by X-ray analysis. According to NMR spectroscopy, the equatorial pyranosylphosphine oxide 8, the sulfide 22, and the borane complex 23 adopt a 4C1 conformation. The axial phosphine oxide 2 is a flattened 4C1, the sulfide 19 exists as a B2,5, and the borane complex 20 is a flattened 4C1 in the solid sate and a B2,5 in solution. Thus, the conformational behavior of these α-D-glucopyranose derivatives reflects the steric requirement of the P-substituents.

Notizen: High-yield chemical syntheses of phosphoramidite building blocks of the four arabinonucleosides aUrd (1), aCyd (2), aAdo (3), and aGuo (4), suitable for (3′-5′)oligoarabinonucleotide synthesis are described. The problem of 2′-hydroxy group protection was solved by introduction of the versatile 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) residue, which was also used for aglycon protection.

Notizen: Formaldehyde reacts with substituted nitrosobenzenes giving the corresponding N-phenylhydroxamic acids. A mechanism involving three sequential steps in this reaction is proposed. The first step is the nucleophilic attack of the nitroso group on the carbonyl group which leads to the formation of the unstable tetrahedral zwitterionic intermediate. This step is followed by the proton transfer to the zwitterionic intermediate to form more stable nitrosocarbinolic cation intermediate, which in the subsequent step undergoes the rate-controlling elimination of proton from the C-atom of nitrosocarbinolic group, leading to the final product, hydroxamic acid. The first and the second step appear to be reversible. The experimental evidence obtained, which is the basis for such a description of the investigated reaction, includes: (a) the order of reactivity of substituted nitrosobenzenes, as demonstrated by the plot of log kobs vs. σ Hammett parameters with slope of -1.74; (b) the observation of a general-acid catalysis; (c) the observation of the inverse solvent deuterium isotope effect of ca. 1.8 in the reaction; (d) the observation of kinetic primary deuterium isotope effect of ca. 8 related to the ‘water’ reaction in the reactions of formaldehyde with substituted nitrosobenzenes; (e) the observation of general-base catalysis in the reaction; (f) the observation of the kinetic primary deuterium isotope effect of ca. 2.1 for the acetate-ion-catalyzed reaction.

Notizen: The Diels-Alder adducts 8 of furan to 1-cyanovinyl acetate were converted into (Methyl 3-chloro)-5-O-(3-chlorobenzoyl)-2, 3-dideoxy-α-dl-arabino-hexofuranosid)uronic acid ((α)-18a) and into (methyl 3-azido-5-O-(3-chlorobenzoyl_-2,3-dideoxy-α-dl-ribo-hexofuranosid)uronic acid ((α)-41a). These compounds were condensed to (3S)-3-[(1′S)-1′-amino-3′-methylbutyl]-3,4-dihydro-8-hydroxyisocoumarin hydrochloride ((-)-2); the resulting mixtures of diastereoisomeric amides were transformed and separated to give the gastroprotective substance AI-77-B((-)-1) and analogues.

Notizen: Aryl-halo-diazirines react under basic conditions with 1,3-cis-, 1,2-cisand 1,2-trans-diols to give acetals. Yields are high. Diastereoselectivities depend upon the diol and upon the reaction conditions. Thus, reaction of the 1,3-cis-diol 1 (Scheme 1) with 2 gave 3 as a single diastereoisomer. The 1,2-cis-diols 4 and 7 led to the endo- and exo-acetals 5/6 (93:7) and 8/9 (ca.10:1), respectively, The 1,2-trans-diols 10, 16, and 19 reacted with 2 to afford 11/12 (90:10), 17/18 (1:1), and 20/21 (6:1), respectively. Reaction of the (4-nitrophenyl)diazirine 13 with 10 at higher temperatures yielded 14/15 (6:4). The uracil moiety, the acetamido group, and the enol-ether moiety are compatible with the reaction conditions. The diastereoselectivity is rationalized on the basis of a reaction sequence involving alkoxy-halogen exchange, which is regioselective or not, thermolysis of the ensuing alkoxydiazirine(s), protonation of the alkoxycarbene to form an (E)-configurated oxycarbenium ion, and attack of the neighboring oxy or hydroxy group, which is only possible for a limited range of conformers.

Notizen: Synthesis of Chiral Cobalt Complexes with Planoid-Tetradentate Ligand SystemThe synthesis of a series of Cbl-related, achiral CoIII complexes 9a-c as well as enantiomerically pure, C2-symmetric CoIII complexes 15 and 18, is reported (Schemes 3, 5, and 7). The crystal structures of 9c and 15 were determined. Complex 18 acts as an enantioselective catalyst in the isomerization of 1,4-epiperoxides to hydroxycycloalkenones.

Notizen: Enantioselective Synthesis of Allyl- and Propargylamines via Nucleophilic 1,2- Addition to Chiral AldininesThe asymmetric Synthesis of allylamines and propargylamines 5 in high enantiomeric purity (e.e. ≤ 97%) is described. Key step is the 1,2-addition of organocerium reagents to chiral α,β-unsaturated aldimines 3 to produce secondary animes 4. The Chiral auxiliary (S,S)-2 is removed in three steps, affording the title compounds 5, useful bifunctional building blocks and compounds of pharmaceutical interest.

Notizen: The synthesis of a series of novel acetylenic compounds 1-7, isolated recently from the fungus Eutypa lata, is described. The crucial step is the coupling reaction between a protected aryl halogenide and the acetylenic chain as a cuprous acetylide (Scheme 1). A more efficient method using bis(triphenylphosphine)palladium dichloride ([Pd(PPh3)2Cl2]) as catalyst was also carried out with success.

Notizen: Fumaramides 3b and 3c bearing the C2-symmetrical pyrrolidine moieties (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine (2b) or 1,3:4,6-di-O-benzylidene-2,5-dideoxy-2,5-imino-L-idit (2c), respectively, as a chiral auxiliary lead to high diastereoselectivities in radical reactions (‘tin method’;Scheme 1). Removal of the chiral auxiliaries affords the corresponding alkylated fumaric acids Scheme 2. Single-crystal X-ray structures of 3b and 3c support arguments that lead to the model of 1,4-stereoinduction.

Notizen: 14O-Ethyl-5m-ethylnaloxone (7) and 14O-ethyl-5-methylnaltrexone (8) have been prepared starting from 14O-ethyl-5-methyloxycodone (9) in several steps. Both, 7 and 8, were found to be opioid antagonists in vitro and in vivo. Compound 7 exhibited some selectivity for μ opioid receptors, whereas compound 8 did not show selectivity for any of the receptor types. In the AcOH-writhing antagonism test, 8 was not able to antagonize morphine-induced antinociception, but antagonized fentanyl- and sufentanil-induced antinociception.

Notizen: Reported here are the novel free porphyrins corallistin B, C, D, and E, isolated as methyl esters 2a, 3a, 4a, and 5a, respectively, from the sponge Corallistes sp. (Lithistida) collected at the basis of the south New Caledonian coral reef. A protocol is also established for formylation of their NiII complexes, which show a different reactivity pattern toward DMF/POCl3 from metal complexes of deuteroporphyrins. Together with corallistin A, Previously isolated as the methyl ester 1a, and the known deuteroporphyrin IX (isolated as 6a) also present in the sponge, the new corallistins, which may be thought to derive from protoporphyrin via heme, account for an amazing 60% of the EtOh extract from the sponge.

Notizen: Synthesis of Selectively N-Functionalized Polyamine DerivativesA threefold differently protected derivative 8 of the triamine spermidine (2) has been prepared in three steps starting from propane-1,3-diamine (1). The protected spermidine derivative 8 was converted to its spermine analogue 12, a useful polyamine intermediate. In a convergent way, the fourfold differently protected derivative 18 of the tetraamine spermine (3) has been obtained by coupling the two different and separately prepared propane-1,3-diamine units 15 and 17. Spermidine derivative 19 and spermine derivative 20, both selectively protected at both primary amino groups, have been Prepared from the free polyamines 2 and 3, respectively, in a direct approach.

Notizen: Cucl2-Induced oxidative coupling of 2-(tert-butyl)-6,6-dimethylpentafulvenyl anion 9 predominantly takes place at C(7) and C(5) to give [7-7] and [7-5] coupling products 15 and 16 in 35 and 47% yields, respectively (Scheme 3) whose structures are elucidated from 1D- and 2D-NMR analysis. Compared with the product distribution observed for 6,6-dimethylpentafulvenyl anion 2 (Scheme 1), no coupling at C(2)/C(3) of 9 is observed. This means that, besides electronic effects, steric effect are also important in oxidative couplings of fulvenyl anions. The same couplings occur in the case of 2,3-bis(6,6-dimethylfulven-2-yl)-2,3-dimethylbutane dianion 10 as well but, due to electronic as well as conformational effects (Scheme 5), intermolecular coupling (to give polymers 17, Scheme 4) is strongly favored over intermolecular coupling. Mechanisms explaining base-catalyzed isomerization 15a ⇄ 15b ⇄ 15c (Scheme 6) as well as isomerization 16a ⇄16b (Scheme 7) are proposed.

Notizen: The Rh1(diolefin)complexes [Rh(nbd)(2)][PF6] [Rh(1,5-cod)(2)][PF6], and [Rh((Z)-α -acetamidocinnamic acid)(2)][PF6] (2 = the chiral P,N-ligand (S)-1-[bis(p-methylphenyl)phospino]-2-[p-methoxybenzyl)amino]-3-methylbutane have been prepared and characterized. These complexes exit as a mixture of isomers arising from different five-membered-ring conformations and diastereoisomers due to both the prochiral nitrogen and olefin ligands. The three-dimensional solutions structures of these complexes have been studied with the specific aim of understanding how the chiral pocket is built. Aspects of the exchange dynamics and their possible relevance to homogeneous hydrogenation are discussed The solid-state structure for the nbd complex, [Rh(nbd)(2)][PF6], as well as detailed one- and two-dimensional 31P-, 13C-, and 1H-NMR results are presented.

Notizen: The 8-amino-5,6,7,8-tetrahydronaphth-2-oic acid (1), 8-(aminomethyl)-5,6,7,8-tetrahydronaphth-2-oic acid (2), and 8-(aminomethyl)naphth-2-oic acid (3) were synthesized in their protected forms as turn-inducing dipeptide mimics. Two of them (2 and 3) were incorporated into a novel type of cyclic, peptide-based structures (see 21 and 34-36) designed as templates for the synthesis of TASP molecules.

Notizen: The stereospecific synthesis of the monoterpene alkaloids (-)-α-skytanthine ((-)-2), (-)-N -demethyle-δ-sky-tanthine((-)-7), and (+)-epidihydrotecomanine (+)-4 was achieved from a common intermediate 22, which in turn was obtained from (1R,4S,1′S)-2-(1′-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene (10),via a ketene aza-Claisen rearrangement. The piperidine derivative (+)-31, formally the aza-analogue of (+)-isoiridomyrmecin, was also obtained from the same intermediate 22.

Notizen: A kinetic study on the alkaline hydrolysis of cephaloridine (1) at pH 10.5 and 37° was carried out using ion-pair reversed-phase HPLC. The main resulting degradation products, the 7-epimer 2 of 1, the Δ2-isomer 3 of 1, and the 3-methylidene compound 4 were identified. The presence of a pyridinio group at C(31) results in a slightly increased formation constant for the 3-methylidene compound 4 and the 7-epimer 2, and introduces a new reaction: the isomerization of the double bond at C(3) in the dihydrothiazine ring to C(2).

Notizen: Treatment of ten monocyclic dienols 8-11 with an excess of fluorosulfonic acid in 2-nitropropane at -90° afforded diastereoisomeric mixtures of racemic tricyclic ethers 12-14 in 81-91% yield (see tables 1 and 2). These transformations represent further examples of biomimetic acid-mediated cyclisations in which an OH group serves as the internal nucleophilic terminator. A non-synchronous process is postulated, and the examples described strongly re-inforce our working mechanistic hypothesis, whereby the stereochemical course of cyclisation is directed by the orientation of the side chain vicinal to the intermediate cyclohexyl cation (see Schemes 4 and 5). It is also demonstrated that the efficiency of this process is independent of the nature of the OH group, which may be primary, secondary, or tertiary. In addition, the organoleptic properties of 12-14, Me homologs of known odorants such as Ambrox® ((-)-3a) and its diastereoisomer, are briefly discussed.

Notizen: Strong bases (lithium diisopropylamide (LDA) or BuLi) convert cyclosporin A (CS) to hexalithio derivative containing a Li alkoxide, four Li azaenolate, and one Li enolate units. The Li6 compound is solubilized in tetrahydrofuran (THF) by addition of excess LDA or LiCl. Reactions with electrophiles (alkyl halides, aldehydes, ClCO2R, CO2, (RS)2, D2O) at low temperatures give products containing new side chains in amino-acid residue 3 of the cyclic undecapeptide (see 1-13, Schemes 1, and 2, and Figs. 1 and 2) in moderate to high yields and, with Re- or Si-selectivities, depending upon the conditions of lithiation of up to 7:1, Pure CS derivatives (Scheme 2, Table 1 in the Exper. Part) can be isolated by column chromatography. N-Alkylations or cleavage of the peptide backbone by carbonyl addition occur only at higher temperatures and/or with prolonged reaction times (see 14 and 15 in Scheme 4). Very little or no epimerization of stereogenic centers occurs under the conditions employed. Possible reasons for the feasibility of these surprizing conversions of CS are discussed (Schemes 4 and 5 and Fig. 3). For comparision, [MeAla3]CS (2b) and [D-MeAla3]CS (2a) were also prepared by conventional peptide synthesis in solution (Schemes 6 and 7). Their 1H- and 13C-NMR spectra are compared with those of CS (Table 2 in the Exper. Part).

Notizen: On Diels-Alder Reactions of the C60-FullereneWe report on the regioselective [4+2] cycloaddition of Buckminsterfullerene C60(1) at room temperature with 2,3-dimethylbuta-1,3-diene and with the monoterpene 7-methyl-3-methylideneocta-1,6-diene (= myrcene) and on the spectroscopic characterization of the corresponding crystalling monoadducts 2 and 3. According to these experiments, 1 acts as a reactive dienophile, which can be functionalized regioselectively under mild and controlled conditons.

Notizen: The Mass Spectral Loss of Water from Macrocyclic Amino-ketonesMacrocyclic oxo-lactams containing an N-alkylamino side chain are stable natural products. Their electron-impact mass spectra are characterized by intensive [M - H2O]+ signals, the molecular ion signal itself is missing. Under electrospray ionization conditions, on the other hand, the [M + 1]+ ion is the only detected signal. The loss of water is explained in terms of an internal (thermal) Schiff-base formation, leading to a e.g. bicyclo[11.9.4]-system. The alcohol corresponding to the macrocyclic ketones and/or lactams show an expected mass-spectral behavior following well known rules.

Notizen: Rigorous regio- and stereospecific labeling experiments are performed to demonstrate the operation of the previously suggested operation of ‘isotopically sensitive branching’ in FeI-mediated C—H bond activation. For the hexane-1,6-diol/Fe+-complex, it is shown that dehydrogenation involves specifically the central C(3)/C(4) position, and the study of the stereospecifically labeled D,L- and meso-[3,4-D2]-isotompomers 1e and 1f demonstrates that dehydrogenation proceedes via two competing pathways (i.e. ‘anti’- vs. ‘syn’-route). The contribution of these routes to the product formation is - due to a kinetic isotope effect - controlled by the relative configuration at the labeled positions C(3)/C(4). For the D,L-form 1e, we estimate a ratio of 49:1 in favor of the ‘anti’-route; due to an isotope effect, this ratio drops to 4.3:1 for the meso-form 1f.

Notizen: Preparation of PQQ in the kag ScaleThe improvement of the PQQ synthesis according to the method of Corey and Tramontano allows the preparation of the triester of this cofactor in the kg scale with an overall yield of 13% (average 78% per step), without a bottleneck in the sequence and with crystalline, analytically pure intermediates. The new purification of free PQQ from conc. H2SO4 is remarkable with respect to the application as well as to the stability of this natural product.

Notizen: The cyclic octapeptide cyclo(-Pro-Pro-Tyr-Val-ProLeu-Ile-Ile-) (1), isolated from the Hymeniacidon sponge, was synthesized and examined conformationally using NMR and molecular-dynamics simulations. Most structural parameters of synthetic 1 are in accord with those reported for the isolated material. Our study indicates some small but significant differences in the assignment of the 1H- and 13C-NMR resonances from those of the natural material. The Conformation was determind in both CHCl3 and DMSO using 1H-NMR and molecular-dynamics simulations. Both NOE's and coupling constants were used as experimental restraints during the simulations which utilized explicitly the same solvent as in the NMR study. The differences in the interaction of the solvent with 1 were examined, providing insight into the observed differenced in conformation. The dominant conformation contains a ßVIa turn about Ile8-Tyr3 including a Pro1-Pro2 cis-peptide bond and a ßI or ßII turn about Val4-Ile7 in CHCl3 and DMSO, respectively.

Notizen: The Diazo-quinone of PQQ as a Possible Reagent for Mapping Quinoproteins by Photo-affinity LabelingPQQ is an organic redox cofactor found in a class of enzymes called quinoproteins. The synthesis and the photochemistry of the diazo-quinones of PQQ and PQQ-triester are described. The photogenerated Wolff-rear-rangement products have been caught with water and methanol as model nucleophiles. The products show a strong fluorescence. The diazoquinone of PQQ may be considered as possible reagent for mapping quinoproteins by photo-affinity labeling.

Notizen: A variety of 2-deoxy-1-O-diphenoxylphosphoryl-hexopyranoses were generated in situ by a radical 2→1 migration of the phosphate group. The structures of the reactive rearrangement products were fully elucidated by NMR spectroscopy. Rate constants for this new rearrangement were determined fro a variety of substrates.

Notizen: Formation of derivatives of PQQ and PQQ-Triester for the Detection of PQQPQQ is an organic redox/cofactor found in a class of enzymes called quinoproteins. It has been reported that materials like milk, egg yolk, vinegar, beer, serum, urine, and biological tissues contain little amounts of PQQ. To facilitate studies on PQQ, a simple detection of PQQ could be extremely useful. For this purpose, we describe in this paper some adducts of PQQ or PQQ-triester with 1,2-diamines, 2,4-dihydroxyaniline, pyrrole, indole as well as an oxidation product of PQQ. UV and fluorimetric detections of these colored products show that this method is relatively sensitive. The reaction of PQQ-triester with (MeO)3P to the phosphole adduct 13 is of great importance: the use of [32P]-labeled trialkyl phosphites will make this reaction an extremely sensitive method to detect PQQ.

Notizen: The elimination of H2O from serine residues in peptides was found to be feasible by the following two steps: O-acylation with AcCl/pyrideine in CH2Cl2 and treatment with an imidine base (DBU or DBN) in THF in the presence of large amounts of LiClO4 (10 examples). Other Li salts such as LiBr and LiCl can also be used. No epimerization of the amino acid residues in te peptide could be detected under these conditions. Thus, a simple method for the preparation of peptides with dehydroalanine residues in high yield, directly from serine-containing precursors, is available.

Notizen: Syntheses of (±)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate (1) and of (±)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (2) are reported. The additon of PhSeCl to 1 afforded (±)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]hept-2-endo-yl acetate (6), whereas 2 added to PhSeCl with the opposite regioselectivity giving (±)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]heptan-2-one (7). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (9) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (10), respectively.

Notizen: Synthesis of a 1,2-trans-Configurated, Equatorial Glycosylphosphonate Analogue of D-myo-Inositol 1,4,5-TrisphosphateThe diphosphonate analogue 3 of D-myo-inositol 1,4,5-trisphosphate (1), a 1,2-trans-configurated, equatorial glycosylphosphonate, was synthesized and characterized as its hexasodium salt 3a. In a first approach, the silylated galactal 4 (Scheme 1) was transformed into the oxirane 5 and hence, by treatment with Me3SiP(OMe)2, into a mixture of the glycosylphosphonate 6 and its silyl ether 7. This mixture was desilylated and then treated with acetone and FeCl3 to yield 8 and 9 (64 and 22%, resp., from 4). In a second approach, the acetates 11/12(Scheme 2) were treated with P(OMe)3/Me3SiOTf in MeCN to afford the anomeric glycosylphosphonates 16/17 (1:1, 60%), while the trichloroacetimidate 10 gave mostly the αD-anomer 16. The αD-anomer 20 was obtained from 12 and P(OPh)3. The highest yield of a β-Dphosphonate was realized by treating 12 with the cyclic phosphite 15 (→ 18/19, 40% each). The β-D-phosphonate 17 was debenzylated (→21) and protected to give 8. Transformation of 8 into the bromide 22 (43%) proved difficult due to the facile demethylation of thephosphonate, and was best followed by treatment of the crude product with CH2N2 and 2,2-dimethoxyporpane. Phosphorylation of 22 yielded 41% of the (dimethoxyphosphoryl)phosphate 23. The conditions of the Arbuzov reaction slowly converted the bromide 23 into the bis(phosphoryl)phosphate 24 (69%), which was then deprotected. The resulting 3 was purified via the ammonium salt and transformed into 3a (72%).

Notizen: Synthetic Analogues of Low-Molecular-Weight Acyl-polyamine Spider ToxinsLow-molecular-weight spider and wasp toxins are selective inhibitors of glutamate receptors of the central nervous system and consist of a polyamine backbone and one or several carboxylic acids and/or amino acids linked by a peptide-like bond. The syntheses of twelve analogues of spider and wasp toxins are described (10a-c, 15a-c, 20a-c, 25a-c) having the general structure of acyl, arylacyl, or heteroarylacyl → DL-alanyl → ω-aminoacyl → N1-spermidine, with variation in the acyl and the ω-aminoacyl part.

Notizen: The reaction of 4-hydroxycoumarin and certain aliphatic aldehydes affords 1:1 or complex 2:2 adducts besides (or in place) of the expected 2:1 bis(coumarin) adducts. Reaction with heptanal, cyclohexanecarbaldehyde, and pivalaldehyde are reported as representative. The structure of the reaction products was established by spectroscopical techniques, including X-ray analysis, and their formation was mechanistically rationalized. Some of the 1:1 adducts are synthetically useful for the preparation of 3-alkyl-4-hydroxycoumarins.

Notizen: The enantioselective copper-catalyzed 1,4-addition of Grignard reagents to α,β-unsaturated carbonyl compounds was studied with the following CuI compounds as catalyst precursor and 1,2:5,6-di-O-isopropylidene-3-thio-α-D-glucofuranose (Hsiig) as chiral ligand: CuI, iodo[bis(dibutylsulfide)]copper(I), [Cu(siig)], [Cu(siig)(pp)] (pp =1,2-bis)(diphenylphosphinoethene), and tetrakis[iodo(tributylphosphine)]copper(I). The addition of BuMg halides to cyclohex-2-en-1-one was tested under several reaction conditions. The chemical yields and regioselectivities for this reaction were, in all cases, larger than 90 and 98%, respectively, and independent of the experimental conditions. The enantioselectivity was strongly dependent on the reaction conditions and reached a maximum of 60%. Several other substrates were also tested in the above reaction. The X-ray crystal structure for [Cu(siig)(pp)] was determined by X-ray crystallography.

Notizen: From the aerial parts of Scrophularia ilwensis, four new triterpene saponins, ilwensisaponins A-D (1-4) were isolated. The structures of the compounds were elucidated using chemical and spectral data as 13β, 28-epoxy-3-β-{{[β-D-glucopyranosyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)]-β-D-fucopyranosyl}-oxy} olean-11-en-23-ol (1), 3-β-{{[β-D-glucopyranosyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)]-β-D-fucopyranosyl}oxy}olena-11, 13(18)-diene-23, 28-diol (2), 3-β-{{[β-D-glucopyranosyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)-β-Dglucopyranosyl-(1→3)]-β-Dfucopyranosyl}oxy}-11α-methoxyolean- 12-ene-23, 28-diol (3), and 3-β-{{[β-D-glucopyransoyl-(1→2)]-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)]-β-D-fucopyranosyl}oxy}olean-12-ene-11α,23,28-triol(4).

Notizen: Prelactones C (3) B (8) were isolated from the concanamycin-producing Streptomyces sp. (strain Gö 22/15) and bafilomycin-producing Streptomyces griseus (strain Tü 2599), respectively, by chemical screening methods. The constitution and relative configuration of 3 and 8 were established by one- and two-dimensional NMR methods. The absolute configuration of 3 was determined using the Helmchen method and that of 8 by CD spectra. The structural properties and absolute configuration of these new δ-lactones reveal strong similarities to the hemiacetal portion of the corresponding macrolide antibiotics. Their possible role in the early polyketide formation of unusual macrolactones is discussed.

Notizen: It is shown that azulene (1) and dimethyl acetylenedicarboxylate (ADM) in a fourfold molar excess react at 200° in decalin to yield, beside the known heptalene- (5) and azulene-1,2-dicarboxylates (6), in an amount of 1.6% tetramethyl (1RS,2RS,5SR,8RS)-tetracyclo[6.2.2.22,501,5]tetradeca-3,6,9,11,13-pentaene-3,4,9,10-tetracarboxylate(‘anti’-7) as a result of a SHOMO (azulene)/LUMO(ADM)-controlled addition of ADM to the seven-membered ring of 1 followed by a Diels-Alder reaction of the so formed tricyclic intermediate 16 (cf. Scheme 3) with a second molecule of ADM. The structure of ‘anti’-7 was confirmed by an X-ray diffraction analysis. Similarly, the thermal reaction of 5,7-dimehtylazulene (3) with excess ADM in decalin at 120° led to the formation of ca. 1% of ‘anti’- 12, the 7,12-dimethyl derivative of‘anti’-7, beside of the corresponding heptalene- 10 and azulene-1,2-dicaboxylated (cf Scheme 2). The introduction of Me groups at C(1)and C(3)of azulene (1) and its 5,7-dimethyl derivative 3 strongly enhance the thermal formation of the corresponding tetracyclic compound. Thus, 1,3-dimethylazulene (2) in the presence of a sevenfold molar excess of ADM at 200° yielded 20% of ‘anti’-9 beside an equal amount of dimethyl 3-mehtylazulene-1,2-dicarboxylate (8;cf. Scheme 1), and 1,3,5,7-tetramethylazulene (4) with a fourfold molar excess of ADM AT 200° gave a yield of 37% of‘anti’-15 beside small amount of the corresponding heptalene- 13 and azulene-1,2-dicarboxylates 14 (cf.Scheme 2).

Notizen: The para-substituted tridentate ligands 2,6-bis[1-(3,5-dimethoxybenzyl)benzimidazol-2-yl]-4′-X-phenyl)-pyridine (X = H: L3; X = NO2: L4; X = NEt2: L5) have been synthesized in six steps using Kröhnke reactions. Spectroscopic results show that the electronic properties of the ligands are strongly influenced by the nature of the substituent bound to the pyridine ring and extended Hückel calculations performed on 4-(X-phenyl)pyridine fragments give a qualitative insight into the factors responsible for the striking differences observed in the absorption spectra. Upon complexation to FeII, the ligands L2-L5 give intensely coloured pseudo-ocatahedral low spin [Fe(Ln)2]2+ (n = 2-5) complexes in acetonitrile solution. Electrochemical and spectroscopic measurements show that the particular electronic characteristics associated with each substituent strongly influence the properties of the resulting FeII complexes as demonstrated by the very intense MLCT transition (∊ 〉 50000 M-1 cm-1) observed in the green complex [Fe(L5)2]2+.

Notizen: Why Pentose-And Not Hexose-Nucleic Acids? Part III. Oligo(2′,3′-dideoxy-β-D-glucopyranosyl)nucleotides. (‘Homo-DNA’): Base-Pairing PropertiesSummary in collaboration with Prof. Dr. C. E. Wintner, Haverford College, Haverford, PA 19041-1392.The paper presents results of a comprehensive investigation on the pairing properties of homo-DNA oligonucleotides, the preparation of which has been described in Part II of this series [2]. The investigation was carried out by using established methods described in the literature for the characterization of oligonucleotides in the natural series, such as determination of melting temperatures of oligonucleotide duplexes by temperature-dependent of melting temperatures, determination of pairing stoichiometry by ratio-dependent UV spectroscopy of binary mixtures of pairing partners, temperature-dependent CD spectroscopy, gel electrophoresis under non-denaturing conditions, and - in selected cases - 1H - and31P-NMR spectroscopy.The systematic comparison of the paring properties of homo-DNA oligonucleotides with corresponding DNA nucleotides (up to dodecamers) indicates that homo-DNA is a highly efficient, autonomous, artificial pairing system with a pairing behavior that is in part similar to, but also, in part, strikingly different from, the pairing behavior of DNA. The pairing properties established so far are listed below in a manner that reflects the sequence of subtitles in Chapt.2 of the text; they were determined under the conditions: H2O, 0.15M NaCl, 0.01M Tris-HCl buffer, pH 7, oligonucleotide concentrations in the μM range, 1:1 ratio of single strands in the case of non-selfcompementary sequences.

Notizen: The syntheses of thiazole and fused thiazolo derivatives 2-4, 6-8, 10a-11b, 13-16 from heterocylic isothiocyanates 1, 5, 9, and 12 bearing an ortho ester group and bifunctional reagents, such as substituted propargylamines, is described. Different regioselectivity of intramolecular nucleophilic attack of the thiourea S-atom on the C ≡ C bond, resulting in the formation of both thiazolo and thiazino derivatives, as well as NMR structure elucidation are discussed.

Notizen: An N methylated residue at the n - 3 position of the chain was used to reduce the maximum number of H-bonds realizable y some D,L-alternating oligopeptides in β4.4-, ↑↑5.6- and ↑↓5.6-helices and thus increase for the oligopeptides, the relative stability of larger β-helices. With D, L-alternating oligoleucines of the series Boc-Leun-OMe, however, this approach did not produce the helices expected. Although ↑↓7.2-helices with only one free NH per strand would theoretically be possible, the N-methylated oligoleucines formed instead flawed β4.4-helices having three free NH's in CHCl3 as well as in other solvents of low polarity. These observations confirm that the stability of β-helices does not depend only on the number of intra-or interstrand H-bonds, and corroborate the idea that β-helices with large cavities are inherently unstable.

Notizen: The stabilities of Zn complexes of cysteine and histidine have been determined together with those with those of three derivatives of each n which one of their three donor functions (carboxyl, amino, and mercapto and imidazole, respectively) has been blocked. Using potentionmetric titrations of aqueous solutions, the 1:1 and 1:2 complexes of all for cysteine- and all four histidine-derived ligands are observed among te various species present (ligands, 1:1 and 1:2 complexes, and protonatd derivatives thereof). All cysteine-derived complexes are more stable than the corresponding histidine-derived complexes by 1-2 orders of magnitude for the 1:1 composition and by 1-6 order of magnitude for the 1:2 composition. For the cysteine series, the sequence of stabilities is cysteine 〉 cysteine ethyl ester ≫ N(α)-acetylcysteine ≫ SMethylcysteine. For the histidine series, the corresponding sequence is histidine 〉 histidine methyl ester 〉 N,N (imidazole)-dimethylhistidine 〉 N(α)-acetylhistidine. The order of stabilities can be explained by the relative strengths of the Zn-S vs. Zn-N coordination, y charge effects, and by chelate ring sizes.

Notizen: The stability constants of the Mn2+, Zn2+, Ni2+, pb2+, and Cd2+ complexes with 1,4,7-triazacylononane-1-acetic acid (noma) were determined at 25° and 0.5M (KNO3) by potentiometric titrations. The species [ML] and [ML(OH)] were found in al cases except for Ni2+, whereas [ML2] was only detected for Cd2+. For the complexes [ML], the order of stability is Mn2+ 〈 Cd2+ 〈 pb2+ 〈 Zn2+ 〈 Zn2+ 〈 Ni2+ 〈 Cu 2+, which is consisten with the Irvin-Williams Series.

Notizen: The tetrameric Cu(β-diketonate) alkoxide complex [Cu(thd)(OCH2CH2OCH3)]4 (thd = 2,2,6,6-tetramethyl-3,5-heptanedionate; 1a) reacts with the alkaline earth metal alkoxides [M(OCH2CH2OCH3)2] (M = Ca, 2a; M = Sr, 2b; M = Ba, 2c) to yield the heteronuclear compounds [Cu2M(thd)3(OCH2CH2OCH3)3] (M = Ca, 6a; M = Sr, 6b). These heterometallic complexes were also obtained in the reaction of 1a and the mixed Ca and Sr complexes of β-diketonate-alkoxide [Mx(thd)y(OCH2CH2OCH3)2x-y] (M = Ca, x = 7, y = 6, 3; M = Sr, x = 5, y = 3, 4), respectively. In comparison, 1a reacts with the analogous [Ba(thd)(OCH2CH2OCH3)] (5a) to yield a[Ba2Cu2(thd)4(OCH3)4(HOCH2CH2OCH3)2] species (8a.) The in situ prepared mixed-ligand Ba Compounds [Ba(thd)OR)] (R = CH2CH2OCH2CH2OCH3, (5b); R = CH2CH2CH2OCH3 (5c) react with the corresponding Cu complexes [Cu(thd)(OR)]n (R = CH2CH2OCH2CH2OCH3), n = 4 (1b); R = CH2CH2OCH2CH2OCH3 (8b); R = CH2CH2CH2OCH3 (8c). However, [Cu(hfd)(OCH2CH2OCH3)]4 (hfd = 1,1,1,5,5,5,-hexafluoroacetylacetonate; 1e) is converted in the presence of 2a-c to the simple metathesis products [M(hfd)2] (M = Ca, Sr, Ba) and [Cu(OCH2CH2OCH3)2]. Crystalline [Ba2Cu2(hfd)2(thd)2(OCH2CH2CH2OCH3)4(HOCH2CH2CH2OCH3)2] (9) was isolated from the reaction of 1a with in situ prepared [Ba((hfd)OCH2CH2CH2OCH3)] (5d) in 2-, methoxyethanol. X-Ray crystallographic structure determinations are reported for 6a, 6b, 8b, and 8c.

Notizen: On the Mechanism of Sequential Radical Cyclization of (Bromomethyl)silyl Ethers of Terpernoid AlcoholsThe cyclic products of the Bu3SnH-promoted radical reaction of (E)-1-[(bromomethyl)dimethylsilyloxy]-2-methylhept-2-ene (6) consists to 98% of a 1:2 mixture of (±)-(4RS,5RS)- and (±)-(4-RS,5SR)-4-butyl-2,2,5-trimethyl-1-oxa-2-silacyclohexane (8a and 8b, respectively). It is, therefore, concluded that the 6-‘endo’→5-‘exo’ tandem cyclization of the 5-mehtyl-3-oxa-2-siladeca-5,9-dien-l-yl radical (reaction 1 → 2) is not necessarily a concerted process, but may be explained as a sequence of individual steps via free-radical intermediates.

Notizen: A Mixture of (3S,6R)- and (3R,6R)-3-methyl-6-(1-methylethenyl)dec-9-enyl acetate (1a and 1b, respectively)-1a being a pheromone of the California red scale - is synthesized in 14 steps from (+)-(R)-limonene (4). The key step is the reductive vitamin-B12-catalyzed coupling of (R)-5-(2-iodoethyl)-6-mehtylhept-6-en-2-one ethylene acetal (8) and methyl crotonate (3).

Notizen: A general way for the functionalization of ribonucleosides is described. The method involves the synthesis of the methyl-ribofuranoside derivative 6 equipped with a linker at the 2-hydroxy group (Scheme 2). After introduction of the nucleic-acid bases under standard conditions (Scheme 3), the resulting β-D-ribonucleosides 8 and 10 are further transformed to derivatives with lipophilic, intercalating, and aminoalkyl residues at the linker moiety. In this way, 2′-modified 5-methyluridines 12, adenosines 13, and 5-methylcytidines 15 and 16 were prepared (Scheme 4).

Notizen: Labeling experiments provide evidence that the Fe1- and CO1-mediated losses of H2 and 2 H2 from tetraline are extremely specific in that both reactions follow a clear syn-1,2-elimination involving C(1)/C(2) and C(3)/C(4), respectively. In the course of the multi-step reaction, the metal ions do not move from one side of the π-surface to the other. Independent experiments confirm that the kinetic isotope effect (KIE) associated with the loss of the first H2 molecule is indeed larger than the KIE for the elimination of the second H2 molecule.

Notizen: The highly active immunosuppressive antibiotic rapamycin is a specific inhibitor of a signal transduction pathway that results in exocytosis and transcription. We report the results of the homo- and heteronuclear NMR experiments of rapamycin in DMSO leading to a complete assignment of the 1H- and 13C-NMR signals. With exception of one CH2 group, all diastereotopic assignments could be achieved using heteronuclear long-range coupling constants. Restrained molecular-dynamics simulation in the same solvent as the NMR experiments led to a well defined conformation of the rapamycin molecule in solution. Differences between the solution and crystal structures are discussed.

Notizen: (o-Hydroxyphenyl)methylphosphonic acids are readily obtained from o-(bromomethyl)- or o-(hydroxymethyl)phenols and trialkyl phosphites. Subsequent hydrolysis leads to the corresponding phosphonic acids. For a series of such compounds, the pKa values have been determined by potentiometry. Their dependence on additional substituents in the aromatic ring is discussed in terms of electronic and steric effects.

Notizen: Crystalline N-hydroxyamino-acid derivatives 4, readily available from non-chiral acyl chlorides 2 and sultams 1, were treated with aldehydes in the presence of NaBH3CN to give N-alkylhydroxylamines 5. N,O-Hydrogenolysis of 5 and saponification of 6 furnished (S)-N-alkylamino acids 7 in high optical purity. Similarly, (R)-N-alkylamino acids 12 were obtained from the antipodal acylsultams 8.

Notizen: A rapid and inexpensive method for the large-scale purification of C60 is the simple filtration of the toluenesoluble extract of commercial fullerene soot through a short plug of charcoal/silica gel with toluene as the eluent. Reactions of C60 with ethyl and tert-butyl diazoacetates in refluxing toluene lead to the formation of the (alkoxycarbonyl)methylene-bridged isomers 1a-3a and 1b-3b, respectively, which can be equilibrated, upon further heating, into the single compounds 1a and 1b, respectively. Isomers 1a/b possess the methano bridge at the 6-6 ring junction, whereas structures 2a/b and 3a/b are bridged at the 6-5 junction. A dramatic influence of local and π-ring current anisotropic effects of the fullerene sphere on the NMR chemical shifts of the methine protons in the bridge is observed: the chemical shifts of the protons located over a pentagon ring in 2a/b and over a hexagon ring in 3a/b differ by Δδ = 3.47 and 3.45 ppm, respectively. The analysis of the 13C-NMR chemical shifts of the bridgehead C-atoms and the 1J(C,H) coupling constants for the methano-bridge atoms reveals conclusively that the 6-5-ring-bridged structures 2a/2b and 3a/3b are π-homoaromatic (‘open’ transannular bond) and the 6-6-ring-bridged structures 1a/b are π-homoaromatic (‘closed’ transannular bond). The electronic absorption spectra show that π-homoconjugation in 2a/b and 3a/b represents a much smaller electronic perturbation of the original C60 chromophore than σ-homoconjugation in 1a/b. The results of this study demonstrate an impressive linkage between the chemistry of methano-bridged annulenes and methano-bridged fullerenes.

Notizen: The cigarette beetle pheromone (-)-serricorole (1) has been synthesized in 23% overall yield by an eight-step sequence starting from N-propionylsultam 3. The synthesis features asymmetric anti- and syn-aldolizations 3 → 4 and 8 → 9, a non-destructive N-acylsultam cleavage with lithiated ethylphenylsulfone (10 → 12), and the smooth, Ti-mediated cyclization of β-acyloxy-ketone 2 to dihydropyranone 14.

Notizen: Synthesis and Pyrolysis of a Triafulvene PrecursorIn view of retro-Diels-Alder reactions (RDA reactions), the triafulvene precursor 3 has been prepared in a simple three-step synthesis by dibromocarbene addition at dibenzo-barrelene (11→12; 44%), halogen-Li exchange followed by methylation (12→14, 100%) and HBr elimination (14→3, 62%) (Scheme 3). Reactivity of the so far unknown bridged 1,1-dibromocyclopropane 12 has been explored, including reductions, allylic rearrangements, and ‘carbene dimerizations’ (Scheme 4). First experiments with respect to the thermal behavior of 3 show that RDA reaction, although occurring in most cases, is not the predominant pathway. When 3 is heated in a sealed tube without solvent, two dimers 26 and 27 are isolated in a total yield of 55% (Scheme 6). On the other hand, gas-phase pyrolysis of 3 at 400° mainly produces rearranged 28 (56%; Scheme 7). It is assumed that bridged trimethylenemethane 29 is an essential intermediate in thermal rearrangements of 3 (Scheme 8).

Notizen: Oxidative treatment of anion 11 (obtained by deprotonation of 6,6-dimethylpentafulvene 10, Scheme 3) with CuCl2 gives a very complex mixture of coupling products 13 (18%), 14 (16%), 15 (36%), 16 (5%), and 17 (6%) (Scheme 4 and Table 2). These results show that the reactive intermediate obtained by oxidation of 11 (which is believed to be the fulvenyl radical 12) has several reactive sites. According to the experiments, reactivity is decreasing in the series C(7) 〉 C(2)/C(3) 〉 C(5) 〉 C(1)/C(4) (Table 2), while simple frontier-orbital considerations would suggest the sequence C(7) 〉 C(5) 〉 C(2)/C(3) 〉 C(1)/C(4). The results suggest that SOMO-SOMO interaction of the approaching fulvenyl radicals 12 is the central effect governing regioselectivity and product distribution, while Coulomb and steric interactions are secondary effects (Table 4).

Notizen: The fluxionality of [Ir4(CO)8(μ2-CO)3L] (L = Br-, I-, SCN-, NO2-, P(4-ClC6H4)3, PPh3, P(4-MeOC6H4)3, P(4-Me2NC6H4)3), as studied by 2D-13C-NMR in solution, is due to two successive scrambling processes: the merry-go-round of six basal CO's and CO bridging to alternative faces of the Ir4 tetrahedron. The basicity of the ligand L has no significant effect on the activation parameters. The scrambling process of lowest activation energy in [Ir4(CO)7(μ2-CO)3(PMePh2)2] correspond to the two possible synchronous CO bridging about a unique face of the metal tetrahedron swapping the relative axial and radial positions of the ligands L. The disubstituted clusters [Ir4(CO)10(μ2-L—L)] with one edge-bridging ligand have a ground-state geometry with three edge-bridging CO's (L—L = bis(diphenylphosphino)methane, bis(diphenylarsino)methane, bis(diphenylphosphino)propane) or with all terminal CO's (L—L = CH3SCH2SCH3). In all cases, the fluxional process of lowest activation energy in the merry-go-round of six CO's about a unique triangular face. For the P and As donor ligands, this process is followed by the rotation of terminal CO's bonded to two Ir-atoms residing on the mirror plane of the unbridged intermediate.

Notizen: Qualitative conformational analysis of the entirety of conceivable hexo- and pentopyranosyl oligonucleotide systems derived from the diastereoisomeric aldohexoses (CH2O)6 and aldopentoses (CH2O)5 predicts the existence of a variety of pairing systems which have not been experimentally investigated so far. In particular, the analysis foresees the existence of a ribopyranosyl isomer of RNA (‘p-RNA’), containing the phosphodiester linkage between the positions C(4′) and C(2′) of neighboring ribopyranosyl units. Double strands of p-RNA oligonucleotides are expected to have a linear structure and to show purine-pyrimidine and purine-purine (Watson-Crick) pairing comparable in strength to that observed in homo-DNA. Experimentally, synthetic β-D-ribopyranosyl (4′→2′)-oligonucleotides derived from adenine and uracil confirm this prognosis: adenine-uracil pairing in p-RNA duplexes is stronger than in the corresponding RNA duplexes. Importantly, adenine in p-Ribo(A8) does not show (reverse-Hoogsteen) self-pairing, in sharp contrast to its behavior in the homo-DNA series. The sheer existence of strong and selective pairing in a system that is constitutionally isomeric to RNA and can be predicted to have a linear structure has implications for the problem of RNA's origin. In this context, a comprehensive experimental study of the pairing properties of p-RNA, of its potential for constitutional assembly, self-replication, and intra-duplex isomerization to RNA seems mandatory.

Notizen: The molecular structure of a chlorophyll a catabolite isolated from the culture medium of bleached Chlorella protothecoides cells has been determined by X-ray diffraction; the crystal structure shows a distorted helical arrangement of the pyrrole rings and consists of symmetrical dimers located at a crystallographic diad, which are stabilized by six intermolecular H-bonds.

Notizen: The synthesis and X-ray structure of the binuclear complex tetrakis[(4S)-4-phenyloxazolidin-2-one]-dirhodium(II) ([Rh2{(4S)-phox}4]) are reported. Structure-selectivity comparisons are made for typical metal carbene transformations, such as inter- and intramolecular cyclopropane formation, intermolecular cyclopropene formation and intramolecular C-H insertions of diazoacetates and diazoacetamides. The enantioselectivity achieved in the [Rh2{(4S)-phox}4]-catalyzed reactions is intermediate between that of [Rh2{(5S)-mepy}4] and [Rh2{(4R)-bnox}4], which were described previously (mepy = methyl 5-oxopyrrolidine-2-carboxylate; bnox = 4-benzyloxazolidin-2-one). In contrast to other catalyzed intermolecular cyclopropane formations, those using [Rh2{(4S)-phox}4] result preferentially in formation of the cis-cyclopropane.

Notizen: A series of dicationic PdII-acetonitrile complexes containing bi- and tridentate nitrogen and bidentate phosphine ligands (some of which are chiral) has been prepared as their BF4 salts. The molecular structures for two of these, [Pd(CH3CN)2(bipy)] (BF4)2 (4) and [Pd(CH3CN)((pybox)(i-Pr))] (BF4)2((S,S)-pybox(i-Pr) = 2,6-bis[(S)-4′-isopropyloxazolin-2′-yl]pyridine, 5) have been determined by X-ray diffraction. All of these complexes are shown to be effective homogeneous catalysts for the aldol-type condensation of the isonitrile, methyl isocyanoacetate, with benzaldehyde. Two isonitrile complexes, [Pd(2,2′-bipyridyl)(CNCH2COOCH3)2] (BF4)2 and [Pd((S,S)-pybox(i-Pr))(CNCH2COOCH3)] (BF4)2, have also been prepared.

Notizen: The hetero-Diels-Alder addition of SO2 to (E)-hexa-1,3-diene (4) gives first 6-ethyl-3,6-dihydro-1,2-oxathiin 2-oxide (= 6-ethylsultine) with the Et group occupying a pseudoaxial position, and then the more stable stereoisomer 6 with the Et substituent in a pseudoequatorial position. The SO2 additions to 1-methoxybuta-1,3-diene (7) and to 1-methoxy-3-[(trimethylsilyl)oxy]buta-1,3-diene (8) give the 6-methoxysultines 9 and 10, respectively, with the MeO groups in pseudoaxial positions and which do not equilibrate with sultines having pseudoequatorial MeO substituents (anomeric effect). A lower limit of ΔΔG = 3.9 kcal/mol was evaluated at -60° for the stabilizing effect arising from the geminal vicinity of a MeO and sulfinate moiety in 3,6-dihydro-6-methoxy-4-[(trimethylsilyl)oxy]-1,2-oxathiin 2-oxide.

Notizen: UV Irradiation of (Z)- and (E)-1(10)-unsaturated 5,10-secosteroids 1-4 in acetone solution effected, besides (Z/E)-isomerization, (i) a stereospecific epoxidation (only in the presence of O2), which, depending on the configuration ((Z) or (E)) in the starting steroid, gave cis-epoxides 5 and 8 (from the (Z)-compounds 1 and 3) or trans-epoxides 6,9, and 10 (from the (E)-compounds 2 and 4), and (ii) oxidative acetone addition to the olefinic double bond producing 1-acetonyl derivatives 7 and 11a, b.

Notizen: The synthesis of [1,5′-3H2]naltrindole (9) with labels at both the morphine skeleton and the indole moiety was carried out by catalytic tritiodehalogenation of 1,5′-dibromonaltrindole (8) resulting in a specific activity of 46.1 Ci/mmol (1705 GBq/mmol). The brominated precursor was prepared by the Fischer indole synthesis starting from 1-bromonaltrexone (7) and (4-bromophenyl)hydrazine.

Notizen: The three new optically active triamines derived from 2,6-bis(aminomethyl)pyridine, i.e. 2,6-bis{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}pyridine (3a), 2,6-bis{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-pyridine (3b), and 2,6-bis{{(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}methyl}pyridine (3c), were synthesized. The equilibrium behaviour in solution and CuII complex formation were studied by acidimetric titration and by UV/VIS and CD measurements. It was found that in aqueous solution, 3a can coordinate one of the CH2OH groups to CuII upon deprotonation. X-Ray crystal structures were determined for the complexes [Cu(3a)Cl]ClO4·H2O, [Cu(3b)Cl]ClO4, and [Cu(3c)Cl]ClO4. In the solid state, coordination of both the OH and the alkoxy groups was observed, and the three ligands are pentacoordinated.

Notizen: Octadienyl carbonates 5 provide cyclic 1,4-dienes 6 when treated with Rh1 complexes (1-10 mol-%) at 80°. Similar cyclization of cyclohexenyl acetate 8 affords cis- fused hexahydroindene 9. Analogous ring closures of nonadienyl carbonate 10 yield preferably the cis-divinypyrrolidine 11 with Rh1 catalysis but the trans-isomer 12 when catalyzed by Pd0. Azaoctadienyl carbonate 5a undergoes elimination with [RhH(PPh3)4] (5 mol-%, 80°) in MeCN giving acyclic triene. 7.

Notizen: Ring-Transformations in the Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirines with 1-Substituted Imidazolidine-2,4,5-trionesReaction of 1-substituted imidazolidine-2,4,5-triones ( = N-substituted parabanic acids; 2) and 3-(dimethylamino)-2,2-dimethyl-2H-azirine (1) in i-PrOH or MeCN at room temperature yields 5,6,7,7a-tetrahydro-3H-imidazo[3,4-a]imidazole-5,7-diones 3 (Scheme 1). By 15N-NMR studies, using (3-15N)-2a, it has been shown that only N(1) in (15N)-3a is labelled and, hence, N(4) stems from 1, e.g. the azirine reacts via cleavage of the N(1)=C(3) bond. In MeCN at room temperature, the azacyclols 3 rearrange slowly to give monocyclic 2H, 5H-imidazol-2-ones 4 (Scheme 3); the 15N-label in (15N)-4a is in position 1. Both reactions proceed via deep-seated skeletal rearrangements, most probably via ring-expansion/ring-contraction processes.

Notizen: Incubation of Spheroplats of Anabaena variabilis (Cyanobacteria) with 22 the 2,6-O-dimetyl-ß-cycoldextrin complex of 2,3-dimethyl-5-phytylhydroquinone (11), revealed the presence of a hitherto unknown enzyme which catalyzes the cyclization of th substrate 11 to give enantiomerically pure γ-tocopherol (3) in ≥ 93% yield.

Notizen: Reaction of 1,3-Thaiazole-5(4H)-thiones and DiazometaneReaction of 4,4-dimethyl-1,3-thiazol-5(4H)-thiones 1 with diazomethane in Et2O at -78° or 0° leads to a mixture of the corresponding 1,4-dithiane 10,1,3-dithiole 11, thiirane 12, 4,5-dihydro-5methylidene-1,3-thiazole 13, and 1,3-thiazol-5(4H)-one 14 (Scheme 3). The structures of 10a, 11a, and 11bhave been established by X-ray crystallography. The formation of the products can be explained via an intermediate thiocaronyl ylide of type E (Scheme 4), generated by the 1.3-dipolar cycloaddition of diazomethane with the exocyclic C=S bond of 1 and elimination of N2. Head-to-head dimerization of E yields 10, 1, 3-dipolar cycloaddition of E and 1 gives the ‘Schönberg product’ 11, and cyclization of E leads to 12, which undergoes a desulfurization to give 13. The thiazolone 141 is formed by hydolysis of E. The similarity of the ratio of the products at -78° and at 0° shows that, in contrast to the reaction of 1 and 2-diazopropane, the elimination of N2 in the primary cycloadduct already occurs at -78°.

Notizen: 3,5,3″,5″-Tetra(tert-butyl)-p-terphenoquinone (12b) was synthesized and characterized by its spectroscopic and X-ray structural data. The ground state of 12b is singlet with a strong contribution of a biradical structure. Paramagnetic derivative of 12b, such as the semiquinone radical anion (12bτ) and its O-protonated form, the phenoxy radical (18), were studied by ESR and ENDOR spectroscopy.

Notizen: A novel type of compound that contains a peptide specific for bacterial peptidoglycans (immunomodulatory activity) and an adamantyl residue (antiviral activity) was synthesized. Thus, L-Ala-D-γGln was linked to DL-Gly(Ada) yielding two diasteroisomers 3a and 3b, i.e. ambo-Gly(Ada)-L-Ala-D-γGln (γGln = isoglutamine-4-amino-4-carbamoylbutanoic acid; Ada = adamantyl). The diastereoisomers were easily separated by column chromatography (silica gel) and characterized, but only the use of a stereospecific enzyme led to the assignment of the configuration of the Gly(Ada) moiety in the two diastereoisomers. The cytotoxic effect and antiviral activity of the novel adamantyltripeptides 3a and 3b, observed as the cell survival and the infectivity reduction of the influenza A virus H1N1 and H3N2 strains, respectively, were studied on MDCK cells in vitro. Both 3a and 3b exhibited low cytotoxicity for MDCK cells and reduced the infectivity of the influenza A virus strains, but to a different extent on different Strain.

Notizen: The Electrospray Mass Spectrometry (ES-MS) of eight different supramolecular complexes shows that the molecular peaks of the desolvated multiply charged cations can be recorded more easily than by Fast-Atom-Bom-bardment Mass Spectrometry (FAB-MS) measurements of similar compound. The preliminary application of the ES-MS technique to self-assembled helical complexes obtained from ligands L3 to L8 with various metal ions (Cu, Co, Eu, Tb) indicates that ES mass spectra qualitatively reflect the species present MeCN solution.

Notizen: The diazirine 1, upon thermolysis or photolysis in either acetone or cyclohexanone, at different concentrations, yield the spiro epoxides 2 and 3, and 4 and 5, respectively (Scheme 1). Yield of 2 and 3 depended both on the temperature and the concentration, and correlated inversely with the yield of the major by-product, the enol-derived glycoside 6. Other by-product were the benzyloxglycal7 and the lactone azines 8. ZnCl2-Promoted methanolysis of 2 under mild condition yielded mixture of the uloside 9 and 10 (1.2:1); similarly, 4 yielded 11 and 12 (1.8:1; Scheme 2). More strongly acidic conditions converted 11 into 12, evidencing that ZnCl2-promoted methanolysis proceeds under kinetic control, which is rationalized. The diazirine 13, upon thermolysis of Photolysis in either acetone of cyclohexanone, yielded the α-D-configurated spiro epoxides 14 and 16, and the α-D-configurated dihydrooxazoles 15 and 17, respectively (Scheme 3), which are either formed by ring-opening of ß-D-epoxides, by competitive interception of the initially formed, hypothetical addition products of the intermediate carbene to the ketones. The glycosylidene carbenes, derived from 1 or 13 are not very reactive towards ketones, yields are good only when sterically unhindered ketones are used in large excess.

Notizen: Swern oxidation of 2,3,4,5-tetra-O-benzyl-D-glucose (1) followed by ammonolysis gave the crystalline amide 3 which was oxidized (DMSO/pyridine · SO3) to yield the oxo-amide 4 and the hydroxy-lactams 5 and 6. Cyclization of 4 to the very slowly equilibrating 5 and 6 was completed by treatment with AcOH in CHCl3. The configuration of the hydroxy-lactams was assigned on the basis of NOEs. Reduction (Et3SiH/BF3 · Et2O) of the hydroxy-lactams either individually or as a mixture led to 2,3,4,6-tetra-O-benzyl-D-gluconolactam (7). The procedure, based upon modifications of a patent, does not require chromatography; the overall yield of 7 from 1 is 43%. Hydrogenolysis of 7 gave D-nojirilactam (8); benzylation led to the known pentabenzyl-D-nojirilactam (9) and to the unsaturated lactam 10.

Notizen: The efficient synthesis of all-cis-[5.5.5.5]fenestrane (2) from the readily available intermediate 3 allowed the electron-diffraction analysis of 2. This structure analysis revealed long C—C bonds in the central C(C)4 fragment and a twist-envelope conformation for the four cyclopentane substructures. The four bridgehead H-atoms are in a synclinal rather than an ecliptic position with an approximate D2 symmetry of 2. Planarizing distortions are evident from the opposite bond angles at the central C-atom being 116.2 ± 0.5° with the remaining four being 103.7 ± 0.2°.

Notizen: [Rh1(η5-azulene)(cod)]+BF4- complexes 3a-g (cod = (Z,Z)-cycloocta-1,5-diene) have been synthesized by reaction of [Rh1(cod)]+BF4- in THF with the corresponding azulenes 1a-g (Table 1). The structure of [Rh1(cod)(η5-guaiazulene)]+BF4- (3a) has been determined by X-ray diffraction analysis (Fig. 1 and 2). The Rh-atom is oriented above the five-membered ring of the azulene with almost equal Rh—C distances to all five C-atoms of the ring. The (Z,Z)-cycloocta-1,5-diene ring occurs in two enantiomorphic distorted (C2v → C2) tub conformations in the crystals (Fig. 3). In CDCl3 solution, the cod ligand in the complexes 3 shows a dynamic behavior on the 1H-NMR time scale which is best explained by rotation of the cod ligand relative to the azulene ligands around an imaginary cod—Rh—azulene axis. The new complexes 3 catalyze the formation of heptalene-1,2-dicarboxylates 2 from dimethyl acetylenedicarboxylate (ADM) and the corresponding azulenes 1 just as effectively as [RuH2(PPh3)4] and the analogous [RhH(PPh3)4] complex in MeCN solution (Table 3). On grounds of simplicity, 3 can be generated in situ, when [RhCl(cod)]2 is applied as catalyst (Table 3).

Notizen: In the context of the hypothesis postlating a heterolytic cleavage of a C—N bond during thermolysis of alkoxydiazirines (Scheme 1), we report the preparation of the diazirines 4, 5, 7, and 8, the kinetic parameters for the thermolysis in MeOH of the diazirines 1 and 4-9, and the products of their thermolysis in an aprotic environment. The diazirines 4, 57, and 8 (Scheme 2-5) were prepared from the known hemiacetals 10, 19, 34 (prepared from 31 in an improved way), and 42 according to an established method. The oximes 11, 20, 35, and 43 were obtained from the corresponding hemiacetals as (E/Z)-mixtures; 43 was formed together with the cyclic hydroxylamine 44. Oxidation of 11, 35, and 43 (N-chlorosuccinimide/1,8-diazabicyclo[5.4.0]undec-7-ene (NCS/DBU) or NaIO4) gave good yields of the (Z)-hydroximolactones 12, 36, and 45, while the oxime 20 led to a mixture of the (E)- and (Z)-hydroximolactones 21 and 22, which adopt different conformations. Their configuration was assigned, inter alia, by a comparison with the enol ethers 28 and 29, which were obtained, together with 30, from the reaction of the diazirine 5 with benzaldehyde and PBu3. Treatment of the hydroximolactone O-sulfonates 13, 23, 37, and 46 with NH3/MeOH afforded the diaziridines 15, 25, 38, and 47 in good yields, while the (E)-sulfonate 24 decomposed readily. Oxidation of the diaziridines gave 4, 5, 7, and 8, respectively. Thermolysis of the diazirines 1 and 4-9 in MeOH yielded the anomeric methyl glycosides 50/51, 16/17, 26/27, 52/53, 39/40, 48/49, and 54/55, respectively. A comparison of the kinetic data of the thermolysis at four different temperatures shows the importance of conformational and electronic factors and is compatible with the hypothesis of a heterolytic cleavage of a C—N bond. An early transition state is evidenced by the absence of torsional strain by an annulated 1,3-dioxane ring. Thermolysis of 1 in MeCN at 23° led mostly to the diasteroisomeric (Z,Z)-, (E,E)-, and (E,Z)-lactone azines 56, 57, and 58 (Scheme 6), which convert to 56 under mild conditions, and to 59 (3%). The benzyloxyglucal 59 was obtained in higher yields (18%), together with 44% of 56-58, by thermolysis of solid 1. Similarly, thermolysis at higher temperatures of 4 in toluene, THF, or dioxane and of 9 in CH2Cl2 or THF yielded the (Z,Z)-lactone azines 60 and 61, respectively, the latter being accompanied by the dihydro-oxazole 62.

Notizen: The synthesis of [Ir2Rh2(CO)12] (1) by the literature method gives a mixture 1/[IrRh3(CO)12] which cannot be separated using chromatography. The reaction of [Ir(CO)4]- with 1 mol-equiv. of [Rh(CO)2(THF)2]+ in THF gives pure 1 in 61% yield. Crystals of 1 are highly disordered, unlike those of its derivative [Ir2Rh2(CO)5(μ2-CO)3(norbornadiene)2] which were analysed using X-ray diffraction. The ground-state geometry of 1 in solution has three edge-bridging CO's on the basal IrRh2 face of the metal tetrahedron. Time averaging of CO's takes place above 230 K. The CO site exchange of lowest activation energy is due to one synchronous change of basal face, as shown by 2D- and VT-13C-NMR. Substitution of CO by X- in 1 takes place at a Rh-atom giving [Ir2Rh2(CO)8(μ2-CO)3X]- (X = Br, I). Substitution by bidentate ligands gives [Ir2Rh2(CO)7(μ2-CO)3(η4-L)] (L = norbornadiene, cycloocta-1,5-diene) where the ligand L is chelating a Rh-atom of the basal IrRh2 face. Carbonyl substitution by tridentate ligands gives [Ir2Rh2(CO)6(μ2-CO)3(μ3-L)] (L = 1,3,5-trithiane, tripod) with L capping the triangular basal face of the metal tetrahedron. Carbonyl scrambling is also observed in these substituted derivatives of 1 and is mainly due to the rotation of three terminal CO's about a local C3 axis on the apical Ir-atom.

Notizen: The monosubstituted [Ir4(CO)11L] clusters (L = P(OPh)3, 1; L = P(OMe)3, 2; L = P(OCH2)3CEt, 3) were obtained in good yields by the reaction of [Ir4(CO)11I]- with the corresponding phosphite. In the solid state, cluster 3 has a Cs geometry with all terminal ligands as shown by an X-ray analysis. Three isomers are present in solution: one with terminal ligands (A) and two with three edge-bridging CO's and with L in axial (B) or radial (C) position (see Scheme). The thermodynamic and kinetic parameters of isomerisations B ⇌ A and A ⇌ C were determined by simulation of the variable-temperature 31P-NMR spectra. The three isomers correspond to three minima on the kinetic pathway of CO scrambling, whose relative energies vary independently within a small range (1-9 kJ mol-1 at 298 K). At low temperature, isomer C is always the least stable and is not observed for 1 which bears the most bulky phosphite ligand. The isomerisations are due to two intramolecular merry-go-rounds of CO groups about two unequivalent faces of the unbridged species A.

Notizen: Variable-temperature and -pressure 13C-NMR studies of the 1,3,5-trithiane-capped triruthenium clusters [Ru3(CO)9{μ3-(η3-1,3,5-trithiane)}] (1) and [Ru3(t-BuNC)(CO)8{μ3-(η3-1,3,5-trithiane)}] (2) revealed that CO site exchanges occur via an intramolecular merry-go-round process, involving a transition state mostly dissociative in character.

Notizen: Title compound 1 was synthesized by a published route which had to be modified (seven steps from readily obtainable starting materials). Characterization of 1 was achieved by spectroscopic means (FAB-MS, 1H-NMR, including 2D-COSY). Furthermore, commercially available reference material purchased for comparison, was unequivocally established to be 10, i.e. incompletely deprotected 1.

Notizen: The 2,3-dihydro-1H-benz[f]indole-4,9-diones 3a-d, h were formed in a one-step reaction in 13-82% yield by an unprecedented [3 + 2] regioselective photoaddition of 2-amino-1,4-naphthoquinone (1) with various electronrich alkenes 2 (Scheme 1, Table). The [3 + 2] photoadducts derived from 1 with vinyl ethers and vinyl acetate gave 1H-benz[f]indole-4,9-diones 4e, f, i, in 33-72% yield, by spontaneous loss of the corresponding alcohol or AcOH from the resulting adducts; 4i has a kinamycin skeleton. The [3 + 2] photoaddition also took place on irradiation of the differently substituted amino-1,4-benzoquinones 6, 7, and 12 and excess alkenes 2 in benzene, giving 1H-indole-4,7-dione derivatives 13 and 14 (Scheme 3), 15a and 16 (Scheme 4), and 18 (Scheme 4), respectively. The initial products in these photoadditions were proved to be hydroquinones, the air oxidation of which yielded the heterocyclic quinones; 2,3-dihydro-2-methoxy-2-methyl-5-phenyl-1H-indole-1,4,7-triyl triacetate (19) was isolated after treatment of the crude photoaddition mixture obtained from 2-amino-5-phenyl-1,4-benzoquinone (7) and 2-methoxyprop-1-ene (2f) with Ac2O and pyridine under N2. A pathway leading to the annelated hydroquinones involving ionic intermediates arising from an electron transfer in these photoadditions is proposed (Scheme 5).

Notizen: O-, S-, and N-Nucleophiles are added to the exocyclic double bond of the title compounds 1. The addition of O- or S-nucleophiles yields stable products (Scheme 1), while addition of N-nucleophiles results in thermally labile compounds (Scheme 2). The reaction is studied by spectroscopic methods. From hydrazine adducts, a spiro[azetidine-3,3′-pyrazolidine] 7 is obtained, and the addition products of methyl- and benzylhydrazine rearrange to pyrazol-4-carboxylates 6. Furthermore, the exocyclic double bond is used for the formation of spiro-β-lactams either by cyclopropane formation or by Diels-Alder reactions (Scheme 4). The steric course of all reactions is studied, and it is shown that all reactions with the double bond occur from the side opposite to the bulkier substitutent at C(4) of the β-lactam ring.

Notizen: The radical cation and the radical anion of ‘syn’-cyclobuta[1,2-c:3,4-c′]di-1,6-methano[10]annulene (‘syn’-4a,12a:6a, 10a-bishomobinaphthylene; 3) have been characterized by their hyperfine data. The highly resolved ESR spectrum of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{+ \atop \dot{}} $\end{document} is dominated by a triplet splitting from the outer pair of methano β-protons (Ho). In contrast, the ESR spectrum of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} is poorly resolved with the largest coupling constants arising from perimeter α-protons. The different hyperfine features of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{+ \atop \dot{}} $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} are rationalized by MO models. The SOMO of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{+ \atop \dot{}} $\end{document} ψSA(b1), has substantial LCAO coefficients of the same sign at the bridged atoms C(1), C(6), C(11), and C(16), whereas in the SOMO of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document}, ψSS(a1), the four atoms lie in the vertical nodal planes. The large width and the reluctance to saturation of the lines in the ESR spectrum of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} are attributed to the near-degeneracy of the lowest antibonding MO's. Due to their similar nodal properties, the SOMO's of \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} and the radical anions of binaphthylene (4), 1,6-methano[10]annulene (1), and naphthalene (2) are interrelated. Moreover, because the cyclic π-systems in 3 and 1 deviate in the same way from planarity, the effect of such distortions on the coupling constants, aHμ, of the perimeter α-protons in \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ 1^{- \atop \dot{}} $\end{document} should be comparable. Indeed, on going from \documentclass{article}\pagestyle{empty}\begin{document}$ 4^{- \atop \dot{}} $\end{document} to \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document}, the |aHμ| values are reduced exactaly by half as much as the corresponding values on passing from \documentclass{article}\pagestyle{empty}\begin{document}$ 2^{- \atop \dot{}} $\end{document} to \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document}, of which the cyclic π-systems are twice contained in \documentclass{article}\pagestyle{empty}\begin{document}$ 4^{- \atop \dot{}} $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ 3^{- \atop \dot{}} $\end{document} respectively.

Notizen: The CH2Cl2 extract of the leaves Annona purpurea L. (Annonaceae) showed strong brine shrimp toxicity and pronounced activity against larvae of the yellow-fever mosquito Aedes aegypti. Activity-directed fractionation of the extract by a combination of column chromatography on silica gel, filtration, and high-pressure liquid chromatography led to the isolation of acetogenins 1-6 as the main active principles. The structures of two novel acetogenins named purpureacin 1(5) and purpureacin 2(6) were elucidated by spectroscopic analysis (UV, EI- and DCI-MS, EI-MS of Me3Si derivatives,1H- and 13C-NMR). The configuration of 5 and 6 was not established due to the limited sample amount. Compounds 3-6 also showed antifungal activity against Candida albicans, and 5 was slightly active against Bacillus subtilis.

Notizen: In a theoretical investigation on Ziegler-Natta catalysis, the influence of the coordination number and ligand type of model compounds in relevant reaction steps were studied. Thus, by using the MEHT method, insertion reactions of ethylene into Zr-CH3 and Zr-H bonds were analyzed in systems of the type [Zr(C2H4)R4R′]-[Zr(Cp)(C2H4)R2R′], and [Zr(Cp)(C2H4)R3R′]-(R=R′=CH3, R=CH3, R′=H). It was found that all processes do not have significant kinetic barriers, whereas the reverse reactions in particular the β-hydride elimination have relatively high ones. The influence of coordination geometry and number on these transformations was found to be insignificant. While studying related conversions starting from [Zr(L)(C2H4)R3R′], [Zr(Cp)(C2H4)RR′(L)]+, and [Zr(Cp)(C2H4)R2R′(L)] (L = π-donor, R=R′=CH3 or R=CH3, R′=H) compounds a pronounced π-donor effect was observed. Methyl insertions in these cases showed a higher computed activation barrier than hydride migrations. An orbital basis for this phenomenon was provided and conclusions concerning chain-length control in Ziegler-Natta catalysis were drawn.

Notizen: Four peri-substituted naphthalene-1-diazonium cations all show short attractive interactions between an electron-rich atom of the peri-substituent and the α -N-atom of the diazonium group. These are interpreted as models for incipient nucleophilic attack on a N≡N bond. The diazonium group is a better acceptor of electron density ‘through space’ than the NO2 group, which parallels their relative ‘through-σ-bond’ inductive effects.

Notizen: UV/VIS Absorption spectra of nitrosubsituted (o-hydroxyphenyl)methylphosphonic acids (o-(phosphonomethyl)phenols) were measured as a function of pH at 25° in 0.1M NaClo4 solutions. Computational treatment of the whole set of optical density data between 200 and 500 nm resulted in the determination of the dissociation constants of these polyacids and also of the individual electronic spectra of all the species involved in the deprotonation sequence. The spectral behavior gives information on the structure of the anions formed and consequently the order of the subsequent deprotonation steps could be deduced. For the (2-hydroxy-3-nitro(or 5-nitro)phenyl)methylphosphonic acid and the 2-hydroxy-5-nitro-1,3-phenylenebis(methylphosphonic acid), the phenolic proton dissociates in the last step, while, in the case of (2-hydroxy-3,5-dinitrophenyl)methylphosphonic acid, the last dissociating proton comes from a P—OH group. An intermediate situation is found for (3-chloro-2-hydroxy-5-nitrophenyl)methylphosphonic acid. Generally, the deprotonation sequence is governed by intramolecular H-bonds involving the phenolic OH group.

Notizen: The glycosylation of the 4-methoxypyrazolo[3,4-d]pyrimidine (5) anion with 1-halo-2-deoxyribose 6 in MeCN/TDA-1 gives N2-deoxynucleoside 9 (29%) together with N1-isomer 7 (48%) and its anomer 8 (6%) [7]. The α-D-anomer 8 is not formed and the yield of the ß-D-anomer 7 increased to 62% when dimethoyethane is used as solvent and [18]crown-6 as catalyst. Employing 1-halo-2,3-dideoxyribose 10 instead of halogenose 6, the 2′,3′ -didexoynucleosides 12 and 14 were formed which desilylated (→ 1b and 2b) and converted into the ddI and ddA derivatives 3b (c7z8Idd), 15b (c7z8Add), and 17 (c7z8A′dd). Contrary to 7-deazapurine nucleotides, the triphosphates of 3b and 15b showed on appreciable activity against HIV-reverse transcriptase.

Notizen: Building blocks derived from 7-deazaguanosine (c7G, 1) were prepared for solid-phase oligoribonucleotide synthesis. Compound 1 was converted into the isobutyurl derivative 2b and the (dimethylamino)methylidene compound 3 (Scheme 1). After tritylation (→ 4a, b), silylation was studied with regard to regioselectivity. It was found that the triisopropylsilyl group in combination with the (dimethylamino)methylidene residue gave the highest 2′ -selectivity (→ 5e). The 2′ -O -silyl derivative 5e was reacted with PCl3 affording the 3′ -phosphonate 7 which was used in solid-phase oligoribonucleotide synthesis. Oligonucleotides derived from U-G-G-G-G-U with an increasing number of c7G residues instead of G were synthesized. Aggregation was studied by polyacrylamidegel electrophoresis and CD Spectroscopy. Disaggregation of the G4-structure of U-G-G-G-G-U was observed when c7G replaced G, demonstrating that guanine N(7) participates in the aggregation process.

Notizen: The catalytic hydrogenation of rifamycin S (2) over Pd/C, followed by oxidation with K3[Fe(CN)6], generates a pair of 16,17,18,19-tetrahydrorifamycins S (3/4), epimeric at C(16). The use of PtO2 as catalyst leads to the hydrogenation also of the C(28)=C(29) bond giving, after oxidation by K3[Fe(CN)6], a mixture of the epimers (16R)- and (16S)-16,17,18,19,28,29-hexahydrorifamycins S (5/6). Furthermore, we synthesized the (16R)- and (16S)-3-bromo derivatives 7/8 and (16R)- and (16S)-3-(piperidin-1-yl) derivatives 9/10. The determination of the X-ray crystal structure of the most abundant epimer 4 of the tetrahydrorifamycins allowed the assignment of the absolute configuration at C(16) of all derivative. A Structure-activity relationship study showed that in general the (16R)-epimers are more potent inhibitors of bacterial RNA polymerase than the (16S)-epimers.

Notizen: X-Ray Crystal-structure analysis of 2,4,8,10-tetrakis(1,1-dimethylethyl)-6,6-dimethyl-12H-dibenzo[d,g][1,3,2]-dioxasilocin showed that its eight-membered organosilicon heterocycle adopts a boat-boat (BB) conformation in the solid state (Figs. 2 and 3).

Notizen: Acid-Catalyzed Reactions of 2-Vinylaniline Derivatives with 1-Benzyl- and 1-Methylpiperidin-4-one: An Elegant Synthesis of New Polycyclic Indole DerivativesThe reaction of 2-vinylaniline derivatives with 1-benzylpiperidin-4-one or 1-methylpiperidin-4-one in toluene at temperatures between 115 and 120° with toluene-4-sulfonic acid as catalyst leads in good yields to a new class of polycyclic indole derivatives (Scheme 1, Table 1). The structure of the new diastereoisomerically pure racemic compounds 1-5 is determined by NMR-spectroscopic methods. A reaction mechanism proceeding via cyclization of enamine 9, leading to a racemic, tricyclic reactive intermediate 10, and subsequent intramolecular 1,5-dipolar cyclization as key steps in proposed for the formation of octahydropyrido[4′,3′:4]cyclobut[1,2-b]indoles 1-5. The scope and limitations of the new method are discussed (see Table 2).