Stereochemical studies of the skipped-polyol polyene macrolide class: Degradation and partial structure determination of mycoticin A and B.

✍ Scribed by Stuart L. Schreiber; Mark T. Goulet

• Book ID: 104228141
• Publisher: Elsevier Science
• Year: 1987
• Tongue: French
• Weight: 323 KB
• Volume: 28
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)96847-3

✦ Synopsis

The degradation of prototype members of the skipped-polyol polyene macrolide class, mycoticins A and B, is reported. The characterization of the resultant fragments allows a partial structure determination to be achieved.

The polyene macrolides comprise a large class of natural products which display potent antiviral and antifungal activity and have been successfully employed in antifungal therapy.1 These compounds selectively alter the permeability of membranes that contain sterols; accordingly, they show activity against yeast, fungi, and eukaryotic cells, but not bacteria.2 The design and synthesis of analogues with increased selectivity towards ergosterol vs. cholesterol, characteristic of fungal and mammalian cells, respectively, should result in fungicides with diminished toxicity and represents a worthy and challenging goal.3 Structural leads are available from selectivity studies that have demonstrated, for example, that phosphatidylcholine vesicles containing ergosterol were markedly more and less sensitive to amphotericin and filipin, respectively, than corresponding preparations containing cholesterol.4 Unfortunately, the interpretation of such structure-function studies is complicated by the paucity of stereochemical information within the polyene macrolide class. Since the discovery of the first polyene macrolide nystatin (now used in antifungal therapy) in 19505, over 200 members have been reported. Although the constitution of over 40 members have been determined, the claim of a full stereochemical elucidation of structure is reserved for a single member of this class, the antiviral, antifungal agent amphotericin B.6,718

A striking feature of a lar equipped with alternating -CH( 8