Straightforward and Facile Approach Toward the N-Derivatization of Pyroglutamates Through Mitsunobu Reaction: Synthesis of N-Alkyl/N-Acyl Pyroglutamates

Abstract

Pyroglutamates have been acknowledged as useful chiral synthons for the synthesis of many bioactive natural products, ACE inhibitors, and conformationally constrained peptides. Though the reactivity differences between two differential carbonyl groups have been well exploited, there is still a dearth of publications on the N-alkylation/acylation of native pyroglutamate as such, due to the relatively low reactivity of NH of pyroglutamates. In the present communication, we report for the first time a simple and efficient methodology for the N-alkylation/acylation of pyroglutamate via Mitsunobu reaction.

Keywords:

• Acylation
• alkylation
• lactam NH
• Mitsunobu reaction
• pyroglutamates

ACKNOWLEDGMENTS

We are extremely thankful to the University Grants Commission for financial assistance in form of a major research project and to SAIF, Central Drug Research Institute, Lucknow, for providing all the spectral data.