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, α‐selective glycosidation proceeded without anomerization of the 2,6‐dideoxy‐β‐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 β‐selective manner was accomplished by activation of the glycosyl imidate with I₂ and Et₃SiH. 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.