Pyroglutamic Acid and its Derivatives: The Privileged Precursors for the Asymmetric Synthesis of Bioactive Natural Products

Abstract

Pyroglutamic acid is one of the privileged asymmetric precursors for the synthesis of a variety of molecules such as Angiotensin-Converting Enzyme (ACE) inhibitors, angiotensin II receptor subtypes (AT-1 receptor antagonists), as well as bioactive natural products. Starting with primary reports in 1980’s, last almost four decades has witnessed a rapid overgrowth of publications using pyroglutamic acid as a preferred asymmetric precursor and these have been well documented. Pyroglutamic acid has two differential carbonyl groups a lactam carbonyl and a carboxylic functionality along with an NH group, and all of these functionalities can be further derivatized/ transformed and in turn opened avenues for the synthesis of variety of molecules. Derived easily from glutamic acid by internal cyclization, pyroglutamic acid offers a cheap and very good source of chirality and has provided an important tool for the synthesis of natural products/intermediates to natural products. Herein, we wish to describe the exploitation of the chemistry of pyroglutamic acid and its derivatives in the asymmetric synthesis of natural products establishing its versatility as a privileged asymmetric precursor.