Synthesis 2015; 47(14): 2088-2092
DOI: 10.1055/s-0034-1380549
paper
© Georg Thieme Verlag Stuttgart · New York

Syntheses of Dap-3 Polymyxin Analogues via a Tris-Boc-Protected Polymyxin B Heptapeptide

Bryan Li*
a   Pfizer Worldwide Research and Development, Groton Laboratories, Groton, CT 06340, USA   Email: bryan.li@Pfizer.com
,
Anne Akin
a   Pfizer Worldwide Research and Development, Groton Laboratories, Groton, CT 06340, USA   Email: bryan.li@Pfizer.com
,
Thomas V. Magee
b   Pfizer Cardiovascular, Metabolic, and Endocrine Diseases (CVMED) Chemistry, Cambridge, MA 02139, USA
,
Carlos Martinez
a   Pfizer Worldwide Research and Development, Groton Laboratories, Groton, CT 06340, USA   Email: bryan.li@Pfizer.com
,
Jan Szeliga
a   Pfizer Worldwide Research and Development, Groton Laboratories, Groton, CT 06340, USA   Email: bryan.li@Pfizer.com
,
Duc Vicki Vuong
a   Pfizer Worldwide Research and Development, Groton Laboratories, Groton, CT 06340, USA   Email: bryan.li@Pfizer.com
› Author Affiliations
Further Information

Publication History

Received: 18 March 2015

Accepted: 19 March 2015

Publication Date:
16 April 2015 (online)


Abstract

A semi-synthesis of a polymyxin (PMB) analogue is described. Commercially available PMB is treated with di-tert-butyl dicarbonate (Boc2O) to give globally protected PMB-Boc5, and the reaction mixture is directly carried to the highly regioselective enzymatic hydrolysis to give the cyclic heptapeptide PMBH-Boc3. After chromatographic isolation, the synthesis is completed by coupling with the tripeptide side chain, deprotection, and salt switch.

Supporting Information

 
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