磷酸酶抑制剂冈田软海绵酸-2末端螺环缩酮结构域的合成与立体化学

Synthesis and stereochemistry of the terminal spiroketal domain of the phosphatase inhibitor dinophysistoxin-2.

作者信息

Forsyth Craig J, Wang Ce

机构信息

Department of Chemistry, The Ohio State University, 100 W. 18th Avenue, Columbus, OH 43210, USA.

出版信息

Bioorg Med Chem Lett. 2008 May 15;18(10):3043-6. doi: 10.1016/j.bmcl.2008.01.002. Epub 2008 Jan 8.

DOI:10.1016/j.bmcl.2008.01.002

PMID:18226903

Abstract

An expedient synthesis of both axially and equatorially C35 methyl substituted spiroketals representing the C28-C38 domain of the potent and selective protein serine/threonine phosphatase inhibitor dinophysistoxin-2 (DTX-2) was developed to enable comparative stereochemical analyses and a stereochemically correct total synthesis of DTX-2. Comparison of proton and carbon NMR data of the synthetic diastereomers with those published for DTX-2 indicates that DTX-2 possesses the (30S *,34R *,35S *)-relative configuration with an axial C35 methyl substituent.

摘要

开发了一种便捷的合成方法，用于合成轴向和赤道向C35甲基取代的螺环缩酮，其代表强效和选择性蛋白丝氨酸/苏氨酸磷酸酶抑制剂冈田软海绵酸-2（DTX-2）的C28-C38结构域，以进行比较立体化学分析和对DTX-2进行立体化学正确的全合成。将合成的非对映异构体的质子和碳核磁共振数据与已发表的DTX-2的数据进行比较，结果表明DTX-2具有(30S *,34R *,35S *)相对构型，且C35甲基取代基为轴向。