Total Synthesis of Pactalactam, an Imidazolidinone-Type Pactamycin Analogue

Abstract

The first total synthesis of pactalactam was accomplished using substrate-controlled stereoselective aziridination and regioselective aziridine ring-opening to construct three continuous amino groups on an octasubstituted cyclopentane core. The cyclopentane framework was obtained by ring-closing metathesis and aldol coupling using a L-threonine-derived oxazoline compound. Cyclic urea formation, m-acetylphenyl group introduction by Chan-Lam coupling, and primary alcohol-selective acylation yielded the reported pactalactam structure. The presence of pactalactam in the fermentation broth of pactamycin-producing bacteria was also confirmed.