SYNTHESIS OF KETOSYL AND ULOSONYL PHOSPHONATES BY ARBUZOV-TYPE GLYCOSIDATION OF THIAZOLYLKETOL ACETATES

Some members of two novel classes of glycosyl phosphonates (galacto, 2 -azido-2-deoxy-galacto, gluco, manno) carrying a diethyl phosphonate a nd a hydroxymethyl (ketosyl derivatives) or carboxymethyl group (uloso nyl derivatives) at the anomeric carbon have been prepared. The synthe tic route involves the trimethylsilyl triflate promoted Arbuzov-type c oupling between thiazolylketol acetates and triethylphosphite to give thiazolylglycosyl phosphonates in good yields (78-93%). This glycosida tion reaction was highly stereoselective giving rise to the alpha-D-gl ycosyl phosphonate as single product with the exception of the reactio n with the gluco derivative which afforded the alpha- and beta-D-anome r in almost equal amount. The phosphono glycosides were converted by t he thiazole-to-formyl deblocking protocol (N-alkylation, reduction, hy drolysis) into aldehydes that in turn served as common intermediates t o ketosyl and ulosonyl diethylphosphonates via reduction or oxidation of the formyl group, respectively. The configuration at the anomeric c arbon of all new compounds was assigned by NMR analysis through the hy drogen-phosphorus coupling constant values and HETNOE experiments. The feasibility of access to the free ketosyl and ulosonyl phosphonic aci ds is demonstrated taking as an example the galactopyranosyl derivativ es. (C) 1998 Elsevier Science Ltd. All rights reserved.