The asymmetric synthesis of erythromycin B
The asymmetric synthesis of erythromycin B
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DOI：
10.1021/ja963575y
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发表时间：
1997-04-02
影响因子：
15
通讯作者：
Hodgson, A
中科院分区：
文献类型：
--
作者：
Martin, SF;Hida, T;Hodgson, A
大环内酯类抗生素红霉素A(1)和B(2)的抗生素活性源于其抑制核糖体依赖性蛋白生物合成的能力，3已成为许多合成研究的对象。然而，尽管有这些努力和各种优雅的调查和方法，只有一个总合成红霉素(1)byWoodward5和正式总合成1报道随后Oishi。6 Tatsuta已经描述了另一种糖基化战略准备1从提炼9 (S) -dihydroerythronolide a 7我们现在报告简洁高效的路线的红霉素抗生素导致的第一个不对称合成红霉素B的登船点红霉素的总合成B (2)是已知的三羟基酮4的三个羟基的差异保护，我们之前以32%的总收率和7个步骤从2-乙基呋喃制备。用于选择特定羟基保护基团的标准对合成的最终成功至关重要，因此值得简要讨论
The macrolide antibiotics erythromycins A (1) and B (2), which owe their antibiotic activity to their ability to inhibit ribosomal-dependent protein biosynthesis, 3 have been the objects of numerous synthetic investigations. 4 However, despite these efforts and a variety of elegant investigations and approaches, there is but a single total synthesis of erythromycin A (1) byWoodward5 and a formal total synthesis of 1 reported subsequently by Oishi. 6 Tatsuta has since described an alternate glycosylation strategy for preparing 1 from naturally-derived 9 (S)-dihydroerythronolide A. 7 We now report a concise and highly efficient route to the erythromycin antibiotics that has resulted in the first asymmetric synthesis of erythromycin B. The point of embarkation for the total synthesis of erythromycin B (2) was the differential protection of the three hydroxyl groups of the known trihydroxy ketal 4, which we had previously prepared in 32% overall yield and seven steps from 2-ethylfuran. 8 The criteria applied to selecting the specific hydroxyl protecting groups was crucial to the eventual success of the synthesis and hence merit brief discussion: Based upon