title: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshida
authors.forename: Richard B
authors.initials: RB
authors.lastname: Silverman
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Arisawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shuto
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D003521:Cyclopropanes / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D003521:Cyclopropanes; D001120:Arginine; C030797:cyclopropane; D019001:Nitric Oxide Synthase