Total synthesis of the Hsp90 inhibitor geldanamycin

被引：56
|
作者：
Oin, Hua-Li
Panek, James S.
机构：
[1] Boston Univ, Dept Chem, Boston, MA 02215 USA
[2] Boston Univ, Ctr Chem Methodol & Lib Dev, Metcalf Ctr Sci & Engn, Boston, MA 02215 USA
来源：
ORGANIC LETTERS | 2008年 / 10卷 / 12期
关键词：
D O I：
10.1021/ol800749w
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
An enantioselective synthesis of the Hsp90 inhibitor geldanamycin was achieved in 20 linear steps and 2.0% overall yield from 2-methoxyhydroquinone. The synthesis is highlighted by a regio- and stereoselective hydroboration reaction; a Sc(OTf)(3)/Et(3)SiH-mediated pyran ring-opening reaction; an enantioselective crotylation to simultaneously install the C8-C9 (E)-trisubstituted olefin, the C10 and C11 stereocenters; a chelation-controlled asymmetric metallated acetylide addition; and an intramolecular copper(I)-mediated aryl amidation reaction to close the 19-membered macrolactam.
引用
收藏
页码：2477 / 2479
页数：3
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