用于HIV-1蛋白酶抑制剂的立体化学确定的新型螺环P2配体的设计与合成。
Design and synthesis of stereochemically defined novel spirocyclic P2-ligands for HIV-1 protease inhibitors.
作者信息
Ghosh Arun K, Chapsal Bruno D, Baldridge Abigail, Ide Kazuhiko, Koh Yashiro, Mitsuya Hiroaki
机构信息
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
出版信息
Org Lett. 2008 Nov 20;10(22):5135-8. doi: 10.1021/ol8020308. Epub 2008 Oct 18.
Abstract
The synthesis of a series of stereochemically defined spirocyclic compounds and their use as novel P2-ligands for HIV-1 protease inhibitors are described. The bicyclic core of the ligands was synthesized by an efficient nBu 3SnH-promoted radical cyclization of a 1,6-enyne followed by oxidative cleavage. Structure-based design, synthesis of ligands, and biological evaluations of the resulting inhibitors are reported.
摘要
描述了一系列立体化学定义的螺环化合物的合成及其作为HIV-1蛋白酶抑制剂新型P2配体的用途。配体的双环核心通过1,6-烯炔的高效nBu 3SnH促进的自由基环化反应，随后进行氧化裂解来合成。报道了基于结构的设计、配体的合成以及所得抑制剂的生物学评价。
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