Total synthesis of polyoximic acid
Total synthesis of polyoximic acid
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DOI：
10.1139/cjc-79-11-1812
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发表时间：
2001-11-01
期刊：
影响因子：
--
通讯作者：
Fu, JM
中科院分区：
文献类型：
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作者：
Hanessian, S;Fu, JM
多酚的降解产物多肟酸的结构和立体化学最初命名为反式-3-亚乙叉-L-叠氮杂环丁烷-2-羧酸。全合成证实其结构为顺式-3-亚乙叉-L-氮杂环丁烷-2-羧酸，并经X-射线单晶学确证。合成了反式异构体，并用X-射线衍射法对其进行了确证。构建四元环的关键步骤是Rh催化的类卡宾插入到β-氨基酸衍生物的N-H键上。外双键的立体选择性是通过进行Horner-Emmons-Wadsworth反应或Wittig反应分别产生反式和顺式异构体来控制的。用Weinreb‘s酰胺作为潜在的甲基，用于分离反式和顺式混合物。通过广泛的2D核磁共振研究，也证实了多氧异辛酸在母体中的双键立体化学为顺式。
The structure and stereochemistry of polyoximic acid, a degradation product of polyoxins, was originally designated as trans-3-ethylidene-L-azetidine-2-carboxylic acid. However, total synthesis revealed that the correct structure was in fact cis-3-ethylidene-L-azetidine-2-carboxylic acid, which was confirmed by X-ray crystallography. The synthesis of the trans-isomer was also done and its identity was confirmed by X-ray analysis as well. The key step for constructing the four-membered ring was a rhodium catalyzed carbenoid insertion into the N-H bond of a beta -amino acid derivative. The stereoselectivity of the exo-double bond was controlled by conducting a Horner-Emmons-Wadsworth or a Wittig reaction to generate the trans- and cis-isomers, respectively. Weinreb's amide was used as a latent methyl group for the separation of trans and cis mixtures. The double bond stereochemistry of polyoximic acid in the parent polyoxin was also confirmed to be cis by extensive 2D NMR studies.