An Expedient Synthesis of LAF389, a Bengamide B Analogue
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- 作者：David D. Xu ; Liladhar Waykole ; John V. Calienni ; Lech Ciszewski ; George T. Lee ; Wenming Liu ; Joanna Szewczyk ; Kevin Vargas ; Kapa Prasad ; Oljan Repi<img src="http ; //pubs.acs.org/images/entities/ccaron.
- 刊名：Organic Process Research & Development
- 出版年：2003
- 出版时间：November 2003
- 年：2003
- 卷：7
- 期：6
- 页码：856 - 865
- 全文大小：179K
- 年卷期：v.7,no.6(November 2003)
- ISSN：1520-586X
文摘
An optimized, convergent, safe synthesis of LAF389 (9), an anti-cancer agent analogous to bengamide B, is described. Startingfrom <IMG SRC="/images/gifchars/alpha.gif" BORDER=0>-D-glucoheptonic (D-glycero-D-gulo-heptonic acid) 
-lactone (10), the lactone 15 was constructed in five steps. Majorimprovements were made in the preparation of the aldehydeprecursor 14 and subsequent olefination to yield 15 via amodified Julia protocol. This olefination was significantlyimproved by using TMSCl as an additive. The second fragmentof the drug substance, 
-caprolactam 7, was obtained in twoone-pot operations from (5R)-5-hydroxy-L-lysine (1). Finally,opening 15 with 7 using sodium 2-ethyl hexanoate (Na-EH) gave8, which on deprotection yielded LAF389.
-lactone (10), the lactone 15 was constructed in five steps. Majorimprovements were made in the preparation of the aldehydeprecursor 14 and subsequent olefination to yield 15 via amodified Julia protocol. This olefination was significantlyimproved by using TMSCl as an additive. The second fragmentof the drug substance, -caprolactam 7, was obtained in twoone-pot operations from (5R)-5-hydroxy-L-lysine (1). Finally,opening 15 with 7 using sodium 2-ethyl hexanoate (Na-EH) gave8, which on deprotection yielded LAF389.