M. Winitz, N. Izumiya
Nov 1, 1964
Citations
0
Influential Citations
2
Citations
Journal
Archives of biochemistry and biophysics
Abstract
Abstract The d-d, l-l, d-l , and l-d stereomers of valyllysine anhydride hydrochloride and phenylalanyllysine anhydride hydrochloride were synthesized for purposes of comparison with the cyclic polypeptide antibiotics. Synthesis was achieved via the dicyclohexylcarbodiimide-mediated condensation of formyl- l (or d )-valine or formyl- l (or d )-phenylalanine with N ϵ -carbobenzoxy- l (or d )-lysine methyl ester, deformylation with methanolic hydrochloric acid of the N ϵ -formyl- N ϵ carbobenzoxydipeptide methyl ester so secured, cyclization of the resulting product with methanolic ammonia to the corresponding N ϵ -carbobenzoxylated 2,5-diketopiperazine, and decarbobenzoxylation of the latter to the desired product by palladium catalyzed hydrogenolysis. All four stereomers of each of the synthetic 2,5-diketopiperazines were insusceptible to the hydrolytic action of proteolytic enzymes, a behavior reminiscent of that of the natural cyclic polypeptide antibiotics; however, none exhibited the antibacterial propensities of the latter. The relationship between the chemical structure of polypeptide antibiotics and their antibacterial properties is discussed.