Synthesis and conformational analysis of a dimerising eight-membered lactamdipeptide

Abstract

The eight-membered lactam dipeptide (3R,8R)-3-acetylamino-8-methoxycarbamoylazocan-2-one was prepared from the L-serine derived (4S)-3-tert-butyloxycarbonyl-4-formyl-2,2-dimethyl-1,3-oxazolidine in 12 steps and 27% overall yield. An extensive conformational analysis both in the solid state and in solution, using NMR, IR and vapour pressure osmometry, was conducted. It was shown that the constrained dipeptide exists in a semi-extended conformation and exhibits a head-to-tail self-recognition (K_dim 100 ± 20 dm³ mol⁻¹ in CDCl₂CDCl₂). This dimerisation appears to be a general phenomenon in a series of cis-disubstituted medium-ring lactam dipeptides.