Stereoselective synthesis and the polyene macrolide antibiotics.
The stereochemical complexity of roflamycoin and other polyene macrolide antibiotics presents a formidable challenge to the synthetic chemist, and the lack of obvious disconnections makes the retrosynthetic analysis very complex. The alternating (1, 3, 5, ...) polyol chain in roflamycoin is difficult to synthesize in part because there is no simple method to assemble these chains from smaller subunits. We have addressed this problem and developed a simple, convergent method for assembling alternating polyol chains. It is designed around a new class of 1,3-diol synthons: 6-alkyl-4-thiophenyl-1,3-dioxanes. These 1,3-diol synthons are readily available from either homoallylic alcohols or beta-hydroxyesters, which are themselves readily prepared in optically pure form. Reduction of these synthons under the appropriate conditions gives configurationally stable alkyllithiums with either syn or anti stereochemistry. Reaction with electrophiles produces protected syn or anti-1,3-diols.
Department of Chemistry, University of Minnesota, Minneapolis 55455.
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Rychnovsky
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018942:Macrolides; D011090:Polyenes / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D018942:Macrolides; D011090:Polyenes