An Efficient Synthesis of 6,6′-DI-O-Acylated α,α-Trehaloses

The potent immunostimulant and antitumor activity of trehalose 6,6′-dimycolates from mycobacteria has led to a great deal of interest in the synthesis of these glycolipids and their analogs.1J To circumvent the formation of 3,6-anhydro derivatives and other by-products resulting from partial protection strategies, many of the synthetic routes to symmetrical 6,6′-diesters (including dimycolates) of trehalose have utilized trehalose intermediates fully protected at the secondary hydroxyl position.2,3 Recently, we described the synthesis of one such intermediate, 2,3,4,2′,3 ′,4′-hexakis-O-trimethylsilyl-aptrehalose (l), directly from trehalose dihydrate via a novel persilylatioddesilylation protocol.4 Diol 1 and related derivatives have been employed in the preparation of trehalose 6,6′-diesters both by direct acylation methods3,5-8 and by nucleophilic displacement of 6,6′-dideoxy derivatives possessing various leaving groups on the 6 and 6′-positions.7-12