Solid-phase synthesis of HTLV-1 protease inhibitors containing hydroxyethylamine dipeptide isostere

Kenichi Akaji, Kenta Teruya, Saburo Aimoto

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

An efficient method has been developed for the first solid-phase synthesis of HTLV-1 protease inhibitors that contain hydroxyethylamine isostere as a transition-state mimetic. The synthetic procedure was designed to allow the evaluation of stereostructure- activity relationships at the scissile site. All the possible configurations at the hydroxy- and side chain-bearing asymmetric centers of the isostere were constructed by an ester-derived asymmetric aldol reaction. Each inhibitor containing the isostere backbone was synthesized on solid support by using the newly developed succinate ester linker. The configuration at the hydroxy- and side chain-bearing asymmetric center showed remarkable effects on the inhibitory activity; the Ki value changed with approximately 2 orders of magnitude. The described approach enables an efficient preparation of the inhibitors containing secondary alcohol as a transition-state mimetic.

Original languageEnglish
Pages (from-to)4755-4763
Number of pages9
JournalJournal of Organic Chemistry
Volume68
Issue number12
DOIs
Publication statusPublished - 2003 Jun 13
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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