Synthetic Studies on the Polyenemacrolide Antiviotic, Pentamycin

多烯大环内酯类抗生素因其强大的抗真菌活性和独特的结构而备受关注。抗生素的结构特征是它们含有1，3-多元醇和全反式多烯部分。我们已经开发了一种有效的立体控制收敛方法来合成1，3-多元醇。以D-甘露醇为原料，通过Brown‘s不对称烯丙基化反应立体选择性地将D-甘露醇制备的丙醛(1)转化为醛(2)，合成了多烯大环内酯类抗生素五霉素(8)。Evans的不对称羟醛缩合得到醇(3)，醇(3)用锌(BH_4)_2立体选择性还原为醛(4)。醛(2)和醛(4)经1，3-多元醇保护和1，3-二硫杂环己烷脱保护后缩合得酮(5)，再用K2CO3在甲醇中反应得到全合成酮。去掉羰基，选择性脱溴，氧化得酮(6)。通过Wittig-Hmer反应成功地实现了多烯部分的伸长，得到了全反式五烯酮(7)。由7合成五霉素(8)目前正在进行中。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