A NEW APPROACH TO THE SYNTHESIS OF GLYCOCONJUGATES

Abstract

1-0-Unsubstituted aldoses afford with trichloroacetonitrile under base catalysis 0-(glycosyl)trichloroacetimidates in high yields. Depending on the reaction conditions either 0-(a-glycosyl) or 0-(ßB-glycosyl)trichloroacetimidates may be obtained highly selectively or even exclusively. The extraordinary diastereoselectivity control is mainly due to stereoelectronic effects. The 0-(a- or B-glycosyl)trichloroacetimidates are stable compounds, which can be isolated easily, quite often as erystalline material. They may be stored for a long period of time. However, upon mild acid catalysis they become strong glycosylating agents. They have proven as versatile intermediates in complex glycosidation reactions with different nucleophiles (0-, S-, N-, and C-nucleophiles). The application of this methodology to the synthesis of glycosphingolipids, glycophospholipid type compounds, and to the synthesis of the tetrasaccharide of the core region of 0-glycoproteins is presented. In addition, the 0-(glycosyl)trichloroacetimidate based synthesis of the repeating unit of Neisseria meningitidis (Serogroup L) will be outlined. Halogenoses and heavy metal salt catalysis are not required in these procedures.