Coenzyme models 51. Structure and reactivity studies of 5-methyl-5-deazaflavinophanes: On the "axial preference" in a flavin redox system

Seiji Shinkai, Noriaki Nishiyama, Tsutomu Matsuda, Ryusuke Kanazawa, Akito Kawase, Osamu Manabe

Research output: Contribution to journalArticle

Abstract

Structures and reactivities of 5-deazaflavins were studied by using new 5-deazaflavinophanes dFl(n) in which N(3) and O(2′) in the 10-(2-hydroxy)phenyl group were linked by a (CH2)n chain (n = 8 and 12). dFl(Bu), having n-butyl groups at N(3) and O(2′), was used as a reference. X-ray crystallographic and 1H NMR studies established that in the Grignard reaction with MeMgBr to yield dFlMered(n) the methyl group attacks the isoalloxazine plane from the axial side and is fixed at the axial position. In NaBH4 reduction of dFlMe(n) to yield dFlMered(n) hydride attacks the isoalloxazine plane from the axial side, but the 5-methyl group is displaced from "equatorial" to "axial" by ring inversion in order to minimize steric hindrance. The axial preference observed for nucleophilic attacks is explained by a stereoelectronic effect. dFlMered(n), having only Heq at the C(5)-position, was much less reactive as reductant than dFlred(n) having both Heq and Hax. The deactivation is rationalized by such that (i) more reactive Hax is lost by substitution with the methyl group and (ii) remaining Heq, surrounded by bulky groups, behaves as a less reactive "buried hydride equivalent". These novei structure-reactivity relationships have important implications on biochemical studies of flavoenzymes.

Original languageEnglish
Pages (from-to)344-358
Number of pages15
JournalBioorganic Chemistry
Volume17
Issue number3
DOIs
Publication statusPublished - Jan 1 1989

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery

Cite this