Organophosphorus Esters of 1-Hydroxy-2-phenylbenzimidazole: Synthesis and Utilization as Novel Peptide Coupling Reagents

Nagnnath D. Kokare; Rahul R. Nagawade; Vipul P. Rane; Devanand B. Shinde

doi:10.1055/s-2007-965918

PAPER

Organophosphorus Esters of 1-Hydroxy-2-phenylbenzimidazole: Synthesis and Utilization as Novel Peptide Coupling Reagents

Nagnnath D. Kokare^a,b, Rahul R. Nagawade^a,b, Vipul P. Rane^a,b, Devanand B. Shinde*^a
^a Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004 (MS), India
^b Wockhardt Research Centre, New Drug Discovery, Aurangabad 431210 (MS), India
e-Mail: dbschemtech@hotmail.com;

Abstract

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Abstract

Highly efficient coupling reagents - phosphoric acid diethyl ester 2-phenylbenzimidazol-1-yl ester, diphenylphosphinic acid 2-phenylbenzimidazol-1-yl ester and phosphoric acid diphenyl ester 2-phenylbenzimidazol-1-yl ester - were designed, synthesized and successfully applied in peptide coupling reactions. Their efficiency was evaluated through the synthesis of a range of amides and peptides, and the extent of racemization was studied by HPLC and found to be negligible. The mechanism of action is probably similar to those found for organophoshorus esters of hydroxybenzotriazole: a presumption supported by the isolation and characterization by mass spectrometry and ¹H NMR of some of the proposed intermediates.

Key words

N-hydroxy-2-phenylbenzimidazole - peptide coupling reagents - HOBt - amide synthesis - minimal racemization

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