Enantioselective Total Synthesis of (+)-Wortmannin

被引：40

作者：

Guo, Yinliang ^{[1
,2
]}

Quan, Tianfei ^{[3
]}

Lu, Yandong ^{[1
,2
]}

Luo, Tuoping ^{[1
,2
,3
]}

机构：

[1] Peking Univ, Coll Chem & Mol Engn, Minist Educ, Key Lab Bioorgan Chem & Mol Engn, Beijing 100871, Peoples R China

[2] Peking Univ, Coll Chem & Mol Engn, Beijing Natl Lab Mol Sci, Beijing 100871, Peoples R China

[3] Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2017年 / 139卷 / 20期

基金：

美国国家科学基金会;

关键词：

PHOSPHOINOSITIDE; 3-KINASE; PHOSPHATIDYLINOSITOL; CONCISE SYNTHESIS; SELECTIVE METHOD; WORTMANNIN; KINASE; INHIBITION; OXIDATION; (+)-XESTOQUINONE; LY294002;

D O I：

10.1021/jacs.7b02515

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A concise and enantioselective total synthesis of the potent PI3K inhibitor (+)-wortmannin is described. A Pd-catalyzed cascade reaction was first developed to connect a synthon derived from Hajos Parrish ketone to a furan moiety. The subsequent Friedel Crafts alkylation of the beta-position of a furan ring to an epoxide was optimized to establish the C10 quaternary center. (+)-Wortmannin was eventually accomplished by transformations following a late-stage oxidation of the furan allylic position. Kinome profiling and in vitro enzymatic assays were performed on 17-beta-hydroxy-wortmannin and an epoxide analogue.

引用

收藏

页码：6815 / 6818

页数：4

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