Synthesis of heptaoxazole macrocyclic analogues of telomestatin and evaluation of their telomerase inhibitory activities

Kazuaki Shibata, Masahito Yoshida, Takashi Takahashi, Motoki Takagi, Kazuo Shin-Ya, Takayuki Doi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

We have demonstrated various synthetic routes to heptaoxazole macrocyclic analogues of telomestatin and evaluated their inhibitory activities against telomerase. We synthesized three heptaoxazole macrocycles consisting of different numbers of methyloxazole moieties and another heptaoxazole analogue with a bromooxazole moiety instead of one of the two methyloxazole moieties found in the structure of telomestatin. The bromooxazole analogue underwent SuzukiMiyaura coupling leading to six analogues having aromatic substituents on the oxazole moiety. The substituents on the oxazole moiety in the heptaoxazole macrocycles, which include a methyl group, a bromine atom, and aromatic substituents, did not affect the inhibitory activity of the overall molecule. In addition, three amine-linked analogues were synthesized by modification of the S-tert-butyl group in the bromooxazole analogue with amine-linked a-bromoacetamides. Notably, one of the amine-linked heptaoxazole analogues exhibited almost the same inhibitory activity as telomestatin.

Original languageEnglish
Pages (from-to)1453-1465
Number of pages13
JournalBulletin of the Chemical Society of Japan
Volume86
Issue number12
DOIs
Publication statusPublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

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