Total synthesis of 12,13-desoxyepothilone B (Epothilone D)

被引：12
|
作者：
Broadrup, RL
Sundar, HM
Swindell, CS
机构：
[1] Protarga Inc, King Of Prussia, PA 19406 USA
[2] Bryn Mawr Coll, Dept Chem, Rosemont, PA 19010 USA
来源：
BIOORGANIC CHEMISTRY | 2005年 / 33卷 / 02期
关键词：
epothilone D; 12,13-desoxyepothilone B; lipase resolution; diastereoselective alkylation; aldol reaction; Suzuki coupling;
D O I：
10.1016/j.bioorg.2004.11.002
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A highly convergent total synthesis of 12,13-desoxyepothilone B (4, Epothilone D) is described involving the coupling of vinyl. iodide (5) and olefin (6). Key steps in the synthesis are the introduction of chirality at C15 via highly enantioselective lipase-mediated enzymatic resolution, diastereoselective alkylation at C8, highly diastereoselective Evans aldol reaction to establish C6-C7, and Mukaiyama aldol reaction to introduce chiral center C3. Palladium catalyzed Suzuki coupling of (5) and (6) provided the methyl ester (27), which was converted to 12,13-desoxyepothilone B (4). (c) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码：116 / 133
页数：18
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