Synthesis of polyozellin, a prolyl oligopeptidase inhibitor, and its structural revision

Bioorg Med Chem Lett. 2018 Mar 1;28(5):930-933. doi: 10.1016/j.bmcl.2018.01.054. Epub 2018 Jan 31.

Abstract

Polyozellin is a p-terphenyl compound which was isolated from Polyozellus multiplex, and exhibits an inhibitory activity against prolyl oligopeptidase (POP). Its structure was assigned as 1 having a p-terphenyl skeleton including a p-substituted dibenzofuran moiety by spectroscopic analyses and chemical means. This paper describes the total syntheses of the proposed structure 1 for polyozellin and its o-isomer 2, revising the structure of polyozellin to the latter. These syntheses involved a double Suzuki-Miyaura coupling using chlorophenylboronic acid as a common key building block, and Cu mediated Ullmann cyclization as key steps. The inhibitory activities of synthetic compounds against POP and cancer cells were also evaluated.

Keywords: Polyozellin; Prolyl oligopeptidase; Suzuki-Miyaura coupling; Ullmann reaction; p-Terphenyl.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology*
  • HL-60 Cells
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Prolyl Oligopeptidases
  • Serine Endopeptidases / metabolism*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Furans
  • polyozellin
  • Serine Endopeptidases
  • PREPL protein, human
  • Prolyl Oligopeptidases