Synlett 2013; 24(3): 323-326
DOI: 10.1055/s-0032-1317919
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© Georg Thieme Verlag Stuttgart · New York

Process Development of Halaven®: Synthesis of the C1–C13 Fragment from d-(–)-Gulono-1,4-lactone

Charles E. Chase, Francis G. Fang, Bryan M. Lewis*, Gordon D. Wilkie, Matthew J. Schnaderbeck, Xiaojie Zhu
  • Pharmaceutical Science & Technology, Eisai Product Creation Systems, Eisai Inc., 4 Corporate Drive, Andover, MA 01810-2441, USA   Fax: +1(978)7944910   Email: Bryan_Lewis@eisai.com
Further Information

Publication History

Received: 13 November 2012

Accepted: 22 November 2012

Publication Date:
10 January 2013 (eFirst)

Abstract

A 12-step kilogram-scale synthesis of the C1–C13 fragment, common to halichondrin B and the totally synthetic analogue Halaven® (E7389, INN eribulin mesylate), is described. The synthesis features four crystalline intermediates which facilitates throughput, and enhances quality control of all stereogenic centers in the title compound.