Axial chirality originating in amide and sulfonamide structures: Flexible stereochemistry of benzo-fused seven-membered-ring heterocycles

Hidetsugu Tabata, Tetsuya Yoneda, Hideyo Takahashi, Hideaki Natsugari

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

The benzo-fused seven-membered-ring nitrogen heterocycles (e.g., 1-benzazepine, 1,5-benzodiazepine, and 1,5-benzothiazepine), which have been used as important core structures of various biologically active molecules, possess a flexible stereochemical (conformational) nature. When exerting biological activity, the receptors and enzymes should recognize the specific conformation of the heterocycles. Conformational change may cause chirality due to the axis. This article describes such axial chirality originating in amide and sulfonamide structures in relation to biological activity Conformation of the benzo-fused seven-membered-ring was frozen by introducing a methyl group at the peri-position of the benzene ring to enable separation of the (aS)/(aR)-axial isomers originating in the sp2-sp2 axis of the Ar-N(CO) and Ar-N(SO2) moieties. Thus, the conformational and atropisomeric properties of 1N-benzoyl-1,5-benzodiazepine (A), 1,5-benzothiazepin-4-one and its S-oxide (B), N-benzoyl-1,5-benzothiazepine and its S-oxide (C), and 1 N-sulfonyl-1,5-benzodiazepine (D) were clarified. In addition, A and C were evaluated as vasopressin receptor ligands to identify the active conformation recognized by the receptor.

Original languageEnglish
Pages (from-to)56-68
Number of pages13
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume74
Issue number1
DOIs
StatePublished - 2016

Keywords

  • 1,5-benzodiazepine
  • 1,5-benzothiazepine
  • Amide
  • Axial chirality
  • Sulfonamide
  • Sulfoxide
  • Vasopressin receptor

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