Methodoloy for the polyene and related antibiotics - enantiospecific synthesis of chiral structural units of amphotericin B from A common progenitor: the C14–C20 and C32–C38 segments
✍ Scribed by Stephen Hanessian; Soumya P. Sahoo; Maurizio Botta
- Publisher
- Elsevier Science
- Year
- 1987
- Tongue
- French
- Weight
- 231 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0040-4039
No coin nor oath required. For personal study only.
✦ Synopsis
Structural units corresponding to the Clc-C2a and C32-C3B segments of amphotericin B were synthesized from a single chiral progenitor. In the previous paper,' we described an efficient and convergent synthesis of the Cl-Cl3 segment of amphotericin B2 starting with (S)-4-hydroxymethyl butyrolactone which is readily available from L-glutamic acid,3 D-ribonolactone,4 or D-mannitol.5 In this paper, we report enantiospecific syntheses of the C 1,+-C20 and CB2-CBB segments of this polyene antibiotic, utilizing the same starting material, namely L-glutamic acid. Recent publications have described other approaches to these two segments based on aldol methodology, 617 on asymmetric alkylation of chiral S-aminoacyl butyrolactones* and the utilization of carbohydrates. ' A semi-synthetic approach for the assembly of amphotericin B is also available." Our novel strategy takes advantage of the replicating lactone technology,11'12 which permits the systematic functionalization of 4-substituted butyrolactones and butenolides.13
Applying this powerfully predictive strategy, it is possible to synthesize stereochemically and functionally defined subunits that match the Cl-C13, C1b-C20 and Ca2-C3B segments of amphotericin B from a single chiral progenitor.