»¯Ñ§Ñ§¿ÆSeminar
Ö÷Ì⣺New strategies and new tragets to combat drug resistance in HIV Chemotherapy: Chemistry meets Virology (HIV»¯ÁÆÒ©ÎïÄâÔì¼ÁµÄ½ÚÔì:»¯Ñ§Ó붾Àíѧ)
»ã±¨ÈË£ºProf. Chris Merier£¨µÂ¹úºº±¤´óѧ)
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ÌáÒª£ºNucleotide glycopyranoses as 1 (e.g. NDP-sugars, sugar nucleotides) are of enormous importance in biology due to their use as key glycosyl donors building blocks in the biosynthesis of oligosaccharides. Moreover, glycosyltransferases that incorporate non-natural monosaccharides or accept non-natural substrates for glycosylation may become a powerful tool for the synthesis of non-naturally occurring bioconjugates. For these reasons an efficient chemical access to these classes of compounds is of high importance. A number of methods have been developed for the synthesis of NDP-sugars 1 but often these protocols involve long reaction times and tedious purifications. Furthermore, the yields are low, and sometimes the stereochemistry at the anomeric center could not be controlled. Here, we present a new, high yielding method of the synthesis using strong-acceptor substituted cycloSal-nucleotides 2 that were used as phosphate active esters [1,2]. CycloSal-triesters 2 were reacted with anomerically pure protected or unprotected glycosyl-phosphates 3 to give NDP-sugars 1 in good to very good chemical yields (up to 88%) after short reaction times and in anomerically pure forms. A great variety of NDP-sugars bearing naturally occurring nucleoside and sugar as well as analogues of both were prepared proving the general applicability of the procedure [3-5]. This method was also used for the synthesis of fluorescence labelled NDP-sugars that was needed for the kinetic characterisation of a glycosyltransferase using FRET, the preparation of nucleotide sugars (NMP-sugars) as well as NDP-disaccharides and trisaccharides¡£