Epimerization of 2'-carbonylalkyl-C-glycosides via enolation, beta-elimination and intramolecular cycloaddition.
Treatment of 2'-carbonyl-alpha-C-glycopyranosides of gluco, galacto, manno, 2-deoxy, and 2-azido sugars with 4% NaOMe resulted in anomeric epimerization to give their respective beta-anomers in good to excellent yields. The epimerization of the 2'-aldehyde of alpha-C-galactopyranoside (10) in deuterium methanol, which afforded the beta-anomer with exclusive deuterium replacements at the 1'-position, excluded the possibility of the exo-glycal as being involved as an intermediate. When 2'-aldehyde (36) and 2'-ketone (41) of 2,3-di-O-benzyl-alpha/beta-l-C-arabinofuranoside were used as substrates we were able to obtain the respective equatorial alpha-C-arabinopyranosides (37 and 42). These observations confirmed that the epimerization involves an acyclic alpha,beta-unsaturated aldehyde or ketone, which is formed by the enolation of 2'-carbonyl-alpha-C-glycoside with subsequent beta-elimination. Thereafter an intramolecular hetero-Michael cycloaddition occurs, leading to the formation of thermodynamically controlled stable products, which were exclusively the equatorial C-glycopyranosides, except in the case of 2'-carbonyl-C-furanosides, where a mixture of two anomers was obtained.
Wang
Zerong
Z
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada.
Shao
Huawu
H
Lacroix
Edith
E
Wu
Shih-Hsiung
SH
Jennings
Harold J
HJ
Zou
Wei
W
D003500:Cyclization; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D006027:Glycosides