Synthetic Studies on the Polyenemacrolide Antiviotic, Pentamycin

多烯大环内酯类抗生素因其独特的结构和有效的抗真菌活性而备受关注。抗生素的结构特征是含有1,3 -多元醇和全反式多烯基团。我们已经开发了一种有效的立体控制聚合合成1,3 -多元醇的方法。我们研究了基于新方法合成多环内酯类抗生素戊霉素(8)的方法。由d -甘露醇制备的醛(1)经布朗不对称烯丙化反应立体选择性转化为醛(2)。Evans不对称醛缩反应生成醇(3)，用Zn (BH_4)_2立体选择性还原生成醛(4)。醛(2)和醛(4)的缩合，1,3 -多元醇的保护和1,3 -二硫烷的脱保护得到酮(5)，用K_2CO_3在甲醇中处理得到全同构酮。去除羰基功能，选择性去甲氧基化和氧化得到酮(6)。通过Wittig-Homer反应成功地实现了多烯部分的延伸，得到了全反式五烯酮(7)。目前正在从7合成戊霉素(8)。JA01KA

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