Conformationally restricted analog and biotin-labeled probe based on beauveriolide III

Takayuki Doi, Terushige Muraoka, Taichi Ohshiro, Daisuke Matsuda, Masahito Yoshida, Takashi Takahashi, Satoshi Mura, Hiroshi Tomoda

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

A conformationally restricted oxazoline analog 7 was designed on the basis of a SAR study of beauveriolide III (2) and its analogs reported previously. Conformational analysis by molecular mechanics calculation suggested that the three side chains of 7 mostly occupy the same spaces as those of 2. The analog 7 was synthesized by peptide coupling of the d-cyclohexylglycine-containing ester 11 and d-Ser-containing dipeptide 12, macrolactamization, and cyclodehydration of 6 for the construction of an oxazoline ring. The bicyclic 7 exhibited potential inhibitory activity for cholesteryl ester synthesis similar to that by 2. These results revealed biologically important 3D spaces of the three side chains in inhibitory activity for cholesteryl ester synthesis. In addition, we accomplished the synthesis of a biotin-labeled probe 8 by copper-catalyzed (3+2) cycloaddition of a biotin-containing alkyne 16 and azido-containing beauveriolide analog 15 prepared from 6.

Original languageEnglish
Pages (from-to)696-699
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

Keywords

  • ACAT inhibitor
  • Beauveriolide
  • Cyclic depsipeptide
  • Molecular probe
  • Oxazoline

ASJC Scopus subject areas

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

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