Synthetic approaches to the C11-C27 fragments of bryostatins.
Synthetic approaches to the C11-C27 fragments of bryostatins.
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DOI：
10.1039/c7ob02127e
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发表时间：
2017-11
影响因子：
3.2
通讯作者：
A. Green;Simon Hardy;E. Thomas
中科院分区：
文献类型：
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作者：
A. Green;Simon Hardy;E. Thomas
改进的Julia反应和酰基碳负离子化学，特别是2-锂化二噻烷的反应，已经被研究用于合成中间体，其是苔藓虫抑制素的C11-C27片段的合成等价物。发现使用2-苯并噻唑砜的改进的Julia反应比使用苯基砜的经典Julia反应更有利于C16-C17双键的形成，并且大体积砜具有非常好的（E）-立体选择性。使用（E）-1-溴丁-2-烯对对应于C19-酰基碳负离子的二噻烷一氧化物进行烷基化是有效的，但是使用对应于苔藓抑素的C20-C27片段的更复杂的烯丙基溴是不成功的，这可能是由于竞争消除反应。这意味着使用C19二噻烷合成20-脱氧苔藓抑素必须涉及从更简单的前体逐步组装C20-C27片段。然而，锂化的C19二噻烷与醛的加合物得到了良好的产率，并且开发了将主要加合物立体选择性转化为甲氧基缩醛的条件，所述甲氧基缩醛对应于20-氧化苔藓抑素的C17-C27片段。随后使用对应于完整C17-C27片段的2-苯并噻唑砜实现了20-脱氧苔藓抑素的C11-C27片段的会聚合成。
The modified Julia reaction and acyl carbanion chemistry, especially reactions of 2-lithiated dithianes, have been investigated for the synthesis of intermediates that are the synthetic equivalents of the C11-C27 fragments of bryostatins. The modified Julia reaction using 2-benzothiazolylsulfones was found to be more useful for the formation of the C16-C17 double-bond than the classical Julia reaction using phenylsulfones, and bulky sulfones gave very good (E)-stereoselectivity. The alkylation of a dithiane monoxide that corresponded to a C19-acyl carbanion using (E)-1-bromobut-2-ene was efficient but the use of a more complex allylic bromide corresponding to the C20-C27 fragment of the bryostatins was unsuccessful, possibly due to competing elimination reactions. This meant that the use of C19 dithianes for the synthesis of 20-deoxybryostatins would have to involve the stepwise assembly of the C20-C27 fragment from simpler precursors. However, lithiated C19 dithianes gave good yields of adducts with aldehydes and conditions were developed for the stereoselective conversion of the major adducts into methoxyacetals that corresponded to the C17-C27 fragment of 20-oxygenated bryostatins. A convergent synthesis of the C11-C27 fragment of a 20-deoxybryostatin was subsequently achieved using a 2-benzothiazolylsulfone corresponding to the intact C17-C27 fragment.