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

Mizuki Watanabe; Kazuya Yamaguchi; Wei Tang; Keisuke Yoshida; Richard B. Silverman; Mitsuhiro Arisawa; Satoshi Shuto

doi:10.1016/j.bmc.2011.08.049

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

Mizuki Watanabe, Kazuya Yamaguchi, Wei Tang, Keisuke Yoshida, Richard B. Silverman, Mitsuhiro Arisawa, Satoshi Shuto^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Pages (from-to)	5984-5988
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	20
DOIs	https://doi.org/10.1016/j.bmc.2011.08.049
State	Published - Oct 15 2011

Funding

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.

Keywords

Arginine analogue
Conformational restriction
Cyclopropane
Nitric oxide synthase
Stereochemical diversity

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2011.08.049

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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.",

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author = "Mizuki Watanabe and Kazuya Yamaguchi and Wei Tang and Keisuke Yoshida and Silverman, \{Richard B.\} and Mitsuhiro Arisawa and Satoshi Shuto",

note = "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. ",

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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.

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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.

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KW - Nitric oxide synthase

KW - Stereochemical diversity

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

Abstract

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Keywords

ASJC Scopus subject areas

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