Synthesis of a series of 3,4-methanoarginines as side-chain conformationally restricted analogues of arginine

Abstract

A series of optically active stereoisomers of 3,4-methanoarginine ( 1– 4 and ent -1– ent -4) with trans/ cis, d / l, and syn/anti stereochemical diversity, the side-chains of which were restricted in various special arrangements, was designed as biologically useful arginine mimetics. These conformationally restricted arginine analogues were synthesized effectively by using a series of chiral 3,4-methanoamino acid equivalents ( 7– 10 and ent -7– ent -10) as the key synthetic units. Their biological evaluation with three isoforms of nitric oxide synthase showed that trans-3,4-methano- l- syn-arginine ( 2) was a good substrate, having close potency to l-arginine, and isoforms selectivities were also similar to those of l-arginine.