A strategy for the solution-phase parallel synthesis of N-(pyrrolidinylmethyl)hydroxamic acids

Both five- and six-membered iminocyclitols have proven to be useful transit ion-state analogue inhibitors of gjlycosidases. They also mimic the transit ion-state sugar moiety of the nucleoside phosphate sugar in glycosyltransfe rase-catalyzed reactions. Described here is the development of a general st rategy toward the parallel synthesis of a five-membered iminocyclitol linke d to a hydroxamic acid group designed to mimic the transition state of GDP- fucose complexed with Mn(II) in fucosyltransferase reactions. The iminocycl itol 8 containing a protected hydroxylamine unit was prepared from D-mannit ol. The hydroxamic acid moiety was introduced via the reaction of 8 with va rious acid chlorides; The strategy is generally applicable to the construct ion of libraries for identification of glycosyltransferase inhibitors.