Combinatorial synthesis of deoxyhexasaccharides related to the landomycin A sugar moiety, based on an orthogonal deprotection strategy.

In this report, we describe the stereoselective synthesis of a combinatorial library comprised of 16 deoxyhexasaccharides that are related to a landomycin A sugar moiety, based on an orthogonal deprotection strategy. The use of an olivosyl donor containing a benzyl ether at the C3 position and benzoyl ester at the C4 position, and the olivosyl donor, a naphthylmethyl ether, and a p-nitrobenzylethyl or benzyl sulfonyl ester enabled the synthesis of a set of four diolivosyl units containing a hydroxyl group at the C3 or C4 position by a simple glycosylation and deprotection procedure. Using a phenylthio 2,3,6-trideoxyglycoside, alpha-selective glycosidation proceeded without anomerization of the 2,6-dideoxy-beta-glycosides. In addition, alkylhydroquinone and levulinoyl groups were found to be an effective set of orthogonal protecting groups for the anomeric position and a hydroxyl group. The coupling of all combinations of trisaccharide units in a beta-selective manner was accomplished by activation of the glycosyl imidate with I(2) and Et(3)SiH. No cleavage of the acid-labile 2,3,6-trideoxyglycoside was observed under the conditions used for the reactions. Finally, all of the protected hexasaccharides were deprotected by hydrolysis of the esters, microwave (MW) assisted cleavage of the 2-trimethylsilylethoxymethoxy (SEM) ether, and a Birch reduction.