2. Academic Validation
  3. Synthesis of polyozellin, a prolyl oligopeptidase inhibitor, and its structural revision

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.
Shunya Takahashi 1,  Takahiro Kawano 2,  Natsumi Nakajima 2,  Yasuaki Suda 2,  Narandulam Usukhbayar 3,  Ken-Ichi Kimura 3,  Hiroyuki Koshino 2
Affiliations

Affiliations

  • 1 RIKEN CSRS, Wako-shi, Saitama 351-0198, Japan. Electronic address: [email protected].
  • 2 RIKEN CSRS, Wako-shi, Saitama 351-0198, Japan.
  • 3 The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Iwate 020-8550, Japan.
PMID: 29429833 DOI: 10.1016/j.bmcl.2018.01.054
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.

Figures