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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Sodium Enolate Derived Reactions of N-Boc and N-benzyl-2-(S)-Pyroglutamates with Electrophiles: Synthesis of 4-Substituted and 2-Substituted Pyroglutamates

Author(s): Jagdish Prasad, Pradeep K. Golay and Sharad K. Panday*

Volume 14 , Issue 3 , 2018

Page: [248 - 253] Pages: 6

DOI: 10.2174/1573407213666161221125542

Price: $65

Abstract

Background: 4-substituted pyroglutamates have found use in the synthesis of ACE inhibitors e.g. Fosinopril, conformationally constrained peptides as well as bioactive natural products. Such versatile applications associated with 4-substituted Pyroglutamates encouraged researchers to study the Lienolate derived alkylation of pyroglutamate with electrophiles. Though several reports are available on Li-enolate derived reactions of pyroglutamates with electrophiles, but sodium-enolate derived reactions of pyroglutamate with electrophiles have not been investigated, and that prompted us to study the behaviour of sodium enolate derived reactions of N-protected pyroglutamates with electrophiles.

Results and Discussion: Herein we have reported our studies on the sodium enolate derived reactions of N-protected pyroglutamate with electrophiles, where N-Boc-(2S)-menthyl pyroglutamate on reaction with various electrophiles in the presence of Sodium hydride afforded 4-substituted pyroglutamates while under similar conditions N-benzyl-(2S)-menthyl pyroglutamate afforded exclusively 2-substituted pyroglutamates.

Conclusion:We have successfully accomplished sodium enolate derived alkylation/aldol reaction on NBoc- (2S)-menthyl and N-Benzyl-(2S)-menthyl pyroglutamate with an objective to synthesize 4– substituted pyroglutamates as well as 2-substituted pyroglutamates. These 4-substituted pyroglutamates and 2-substituted pyroglutamates have potential to serve as intermediate for the synthesis of bioactive natural products, ACE inhibitors and conformationally restricted peptide analogs.

Keywords: Sodium enolate derived reactions, aldol reaction, alkylation, 4- substituted pyroglutamates, 2- substituted pyroglutamates.

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