Synthesis of the C29-C44 portion of spongistatin 1 (altohyrtin A).
Synthesis of the C29-C44 portion of spongistatin 1 (altohyrtin A).
复制标题
海绵抑素 1（altohyrtin A）的 C29-C44 部分的合成。
DOI：
10.1021/jo0002801
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Heathcock,CH
中科院分区：
文献类型：
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作者：
Wallace,GA;Scott,RW;Heathcock,CH
海绵抑素 1（altohyritin A）的 C29−C44 部分的两种合成方法已经开发出来。第一种方法的关键步骤依赖于glucal18的克莱森重排以提供酯20a。将该中间体进一步转化为硅烯醇醚 30，在 Mukaiyama 醇醛条件下与醛 3 偶联。这种羟醛加合物的环化完成了我们对海绵抑素 1 C29−C44 部分的首次合成，总共需要 25 个步骤，最长线性序列（21 个步骤）的产率为 2.4%。我们还开发了基于 glucal43 C-糖苷化的第二代方法。通过平衡相应的C-糖苷49a/带50a/b，以良好的产率获得所需的C-糖苷(50a)。该酮的醇醛缩合提供环化前体67，其经历酸催化缩酮化以闭合海绵抑素的E环。采用氧化/还原方案设定 C37 立构中心。对 C37 醇的保护和 C44 醇的选择性揭露完成了我们的第二代合成。该方法需要 27 个步骤，最长线性序列（18 个步骤）的产率为 13.2%。
Two synthetic approaches to the C29−C44 portion of spongistatin 1 (altohyritin A) have been developed. The key step of the first approach relies on the Claisen rearrangement of glucal18to provide ester20a. This intermediate was advanced to silyl enol ether30, which was coupled under Mukaiyama aldol conditions with aldehyde3. Cyclization of this aldol adduct completed our first synthesis of the C29−C44 portion of spongistatin 1, requiring 25 total steps and occurring in 2.4% yield over the longest linear sequence (21 steps). We have also developed a second-generation approach based on the C-glycosidation of glucal43. Through equilibration of the corresponding C-glycosides49a/band50a/bthe desired C-glycoside (50a) was obtained in good yield. Aldol condensation of this ketone provided cyclization precursor67, which undergoes acid-catalyzed ketalization to close theE-ring of the spongistatins. An oxidation/reduction protocol was employed to set the C37 stereocenter. Protection of the C37 carbonol and selective unmasking of the C44 carbonol completed our second generation synthesis. This approach requires 27 steps and occurred in 13.2% yield over the longest linear sequence (18 steps).