Synthetic Studies on the Polyenemacrolide Antiviotic, Pentamycin

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The polyens macrolide antibiotics have attracted much attention for their potent antifungal activity and unique structure. The characteristic structural feature of the antibiotics is that they involve 1, 3-polyol and all-trans-polyene moieties. We have already developed an effective and stereocontrolled convergent method for the synthesis of 1, 3-polyols. We have studied the syntheis of the polyens macrolide antibiotic, pentamycin (8), based on the newly developed method.Aldehyde (1), prepared from D-mannitol, was converted to aldehyde (2) stereoselectively via Brown's asymmetric allylation. Evans' asymmetric aldol condensation gave alcohol (3), which was converted to aldehyde (4) via the stereoselective reduction using Zn (BH_4)_2. Condensation of both aldehydes (2) and (4) followed by protection of 1, 3-polyols and deprotection of 1, 3-dithiane gave ketone (5), which was treated with K_2CO_3 in methanol to give all-syn-ketone. Removal of the carbonyl function, selective debrenzylation, and oxidation gave ketone (6). Elongation of polyens moiety was achieved by Wittig-Homer reaction successfully to give all-trans-pentaenone (7). Synthesis of pentamycin (8) from 7 is now in progress.JA01KA