Total synthesis and study of 6-deoxyerythronolide B by late-stage C-H oxidation.
Total synthesis and study of 6-deoxyerythronolide B by late-stage C-H oxidation.
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在21世纪世纪的化学前沿挑战中，增加复杂分子结构的合成效率和多样性是相互关联的目标。C-H氧化反应，特别是当应用于复杂分子合成的后期阶段时，对于实现这两个目标具有特殊的希望。在这里，我们报告了一个后期阶段的C-H氧化策略，在全合成6-脱氧阿糖胞苷B（6-dEB），红霉素抗生素的糖苷配基前体。使用以高区域选择性、化学选择性和非对映选择性（>40：1）进行的后期（步骤19/22）C-H氧化大环内酯化反应将高级中间体环化为6-dEB的14元大环核心。大环内酯化的螯合物控制模型预测了C-O键形成的立体化学结果，并指导了合成第一个非对映异构体13-epi-6-dEB前体的条件的发现。总的来说，这种C-H氧化策略提供了红霉素核心的高效和立体化学通用合成。
Among the frontier challenges in chemistry in the 21st century are the interconnected goals of increasing synthetic efficiency and diversity in the construction of complex molecules. C—H Oxidation reactions, particularly when applied at late-stages of complex molecule syntheses, hold special promise for achieving both these goals. Here we report a late-stage C—H oxidation strategy in the total synthesis of 6-deoxyerythronolide B (6-dEB), the aglycone precursor to the erythromycin antibiotics. An advanced intermediate is cyclized to the 14-membered macrocyclic core of 6-dEB using a late-stage (step 19 of 22) C—H oxidative macrolactonization reaction that proceeds with high regio-, chemo-, and diastereoselectivity (>40:1). A chelate-controlled model for macrolactonization predicted the stereochemical outcome of C—O bond formation and guided the discovery of conditions for synthesizing the first diastereomeric 13-epi-6-dEB precursor. Overall, this C—H oxidation strategy affords a highly efficient and stereochemically versatile synthesis of the erythromycin core.