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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Pages (from-to)5984-5988
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number20
DOIs
StatePublished - 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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