Synthesis and analysis of the sterically constrained L-glutamine analogues (3S,4R)-3,4-dimethyl-L-glutamine and (3S,4R)-3,4-dimethyl-L-pyroglutamic acid

The nonproteinogenic amino acids (3S,4R)-3,4-dimethyl-L-pyroglutamic acid and (3S,4R)-3,4-dimethyl-L-glutamine-found in the cyclic depsipeptides callipeltin B, callipeltin A, and papuamide A-were synthesized from a common intermediate derived from L-pyroglutamic acid. The diastereoselective introduction of the methyl groups was accomplished by cuprate addition and enolate alkylation, followed by a kinetic epimerization of the C-4 methyl substituent. (3S,4R)-3,4-Dimethyl-L-glutamine shows a conformational restriction of its side chain which may be related to its biological function in the natural products where it is found. (C) 2001 Elsevier Science Ltd. All rights reserved.