The disarming effect of the 4,6-acetal group on glycoside reactivity: Torsional or electronic?

Henrik Helligsø Jensen, Lars Ulrik Nordstrøm, Mikael Bols

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

An evaluation of whether the well-known deactivating effect of a 4,6-acetal protection group on glycosyl transfer is caused by torsional or an electronic effect from fixation of the 6-OH in the tg conformation was made. Two conformationally locked probe molecules, 2,4-dinitrophenyl 4,8-anhydro-7-deoxy- 2,3,6-tri-O-methyl-β-D-glycero-D-gluco-octopyranoside (18R) and the L-glycero-D-gluco isomer (18S), were prepared, and their rate of hydrolysis was compared to that of the flexible 2,4-dinitrophenyl 2,3,4,6-tetra-O-methyl- β-D-glucopyranoside (21) and the locked 2,4-dinitrophenyl 4,6-O-methylidene-2,3-di-O-methyl-β-D-glucopyranoside (26). The rate of hydrolysis at pH 6.5 was 21 > 18R > 18S > 26, which showed that the deactivating effect of the 4,6-methylene group is partially torsional and partially electronic. A comparison of the rate of acidic hydrolysis of the corresponding methyl α-glycosides likewise showed that the probe molecules 17S and 17R hydrolyzed significantly slower than methyl tetra-O-methyl- glucoside 19, confirming a deactivating effect of locking the saccharide in the 4C1 conformation. The experiments showed that the hydroxymethyl rotamers deactivate the rate of glycoside hydrolysis in the order tg ≫ gt > gg.

Original languageEnglish (US)
Pages (from-to)9205-9213
Number of pages9
JournalJournal of the American Chemical Society
Volume126
Issue number30
DOIs
StatePublished - Aug 4 2004
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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