Novel zinc (II)-mediated epimerization of 2'-carbonylalkyl-alpha-C-glycopyranosides to their beta-anomers.
2'-Aldehydes and 2'-ketones of alpha-C-glycosides, including the gluco-, galacto-, and manno- series, were epimerized exclusively to their beta-anomers in good-to-excellent yields under basic conditions and in the presence of zinc acetate. The beta-stereoselectivity is independent of the neighboring group at 2-O-substitution of sugar substrates. Therefore, this provides a particularly useful method for the preparation of manno-beta-C-glycosides. The epimerization is likely initiated by the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chair-boat structure. Due to the activation generated by the Zn-O coordination, fission of the C1-O bond occurs, leading to opening of the pyranose ring, which is spontaneously followed by a change in conformation. The more stable anti chair-boat transition state is favored, and the subsequent hetero-intramolecular Michael addition results in the formation of beta-C-glycoside in a ring-closure step.
Shao
Huawu
H
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada.
Wang
Zerong
Z
Lacroix
Edith
E
Wu
Shih-Hsiung
SH
Jennings
Harold J
HJ
Zou
Wei
W
D002236:Carbohydrate Conformation; D002384:Catalysis; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D019345:Zinc Acetate / Q000737:chemistry*
D006027:Glycosides; D019345:Zinc Acetate