ISSN:
0170-2041
Keywords:
Myxovirescins
;
Myxococeus virescens MX v48
;
Suzuki coupling
;
Macrolides
;
Lactones
;
Lactams
;
1,3-Dioxolanes
;
1,3-Dithianes
;
Antibiotics
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
In this and the following two papers the synthesis of myxovirescins A1, A2 and M2, 28-membered macrocyclic lactam-lactones with antibiotic acitivity, is described. A retrosynthetic analysis of the myxovirescin family of ca. 30 target molecules leads to a strategy which could be applied to approximately half of them by slight variations of the building blocks used (Schemes 1-3 and following paper). The southeastern part of the molecule, containing the atoms O(1)-C(14) of myxovirescins A and M is described in this first paper (Scheme 3). The assembly is achieved by using the following appropriately protected units: (S)-2-hydroxy-pentanoic acid, ([1,3]dithian-2-ylmethyl)-amine (Scheme 4), the triflate of (S,R)-2,2-dimethyl-5-vinyl-[1,3]dioxolan-4-ylmethanol, (E)-3-bromo-2-buten-1-ol, and (E)-2-bromo-2-buten-1,4-diol (Scheme 5), the starting materials for these being malic acid, aminoacetaldehyde, ribose, crotyl alcohol and butyne-1,4-diol. The building blocks are put together by using the following key steps: Kolbe electrolysis, amide formation, lithiodithiane alkylation, and Suzuki coupling (Schemes 6 and 8). The only newly created chirality center [C(6) of the target molecules] is generated stereoselectively by a Li-selectride reduction/Mitsunobu inversion (Table 1, Scheme 7). The termini of the O(1)-C(14) fragment (2 in Scheme 8) carry a (protected) hydroxy acid and an aldehyde group for the Julia coupling and lactonization, respectively, in the final steps of the synthesis. All intermediates are fully characterized. The X-ray crystal structures of two compounds prepared for incorporation as N(4)-C(11) and as C(12)-C(14) of the target molecules are also described (Figures 1 and 2).
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jlac.199419940712
Permalink
