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

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.

Figure optionsDownload as PowerPoint slide