TY - JOUR
T1 - Synthesis of a series of 3,4-methanoarginines as side-chain conformationally restricted analogues of arginine
AU - Watanabe, Mizuki
AU - Yamaguchi, Kazuya
AU - Tang, Wei
AU - Yoshida, Keisuke
AU - Silverman, Richard B.
AU - Arisawa, Mitsuhiro
AU - Shuto, Satoshi
N1 - Funding Information:
This study was supported by the Japan Society for the Promotion of Science (Grant-in-Aid for Young Scientists 20890002 to M.W. and Grant 21390028 to S.S.) and the Uehara Memorial Foundation (to M.W.). The authors are grateful to Sanyo Fine Co., Ltd for the gift of the chiral epichlorohydrins.
PY - 2011/10/15
Y1 - 2011/10/15
N2 - 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.
AB - 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.
KW - Arginine analogue
KW - Conformational restriction
KW - Cyclopropane
KW - Nitric oxide synthase
KW - Stereochemical diversity
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U2 - 10.1016/j.bmc.2011.08.049
DO - 10.1016/j.bmc.2011.08.049
M3 - Article
C2 - 21917467
AN - SCOPUS:80053254485
VL - 19
SP - 5984
EP - 5988
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 20
ER -