For some years our laboratory has been interested in the synthesis of cord factor (6,6'-di-O-mycoloyl-~,#-trehalose) and cord-factor analogues, and several syntheses of this class of biologically impo~ant compounds have been described'-', involving 2,3,4,2',3' ,4'-hexa-O-benzyl-~,~-trehalose (2) as the keyinter-mediate2a3. Compound 2 was obtained by successive tritylation of anhydrous trehalose, alkali-catalyzed perbenzylation with benzyl chloride, and detritylation of the purified or crude 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-ditrityl trehalose (1) with 80% aqueous acetic acid. The resulting hexa-0-benzyltrehalose (2) was then purified from a byproduct by chromatography on silica ge12y3. The i.r. spectrum of the byproduct suggested that it was probably a 6-monoacetate (3) of hexa-0-benzyl trehalose (absorption at 1370,1745, and 3300 cm-'), and we were able to eliminate it and improve the yield of 2 ~nsiderabIy by brief alkaline hydrolysis of the detritylation mixture. However, we were intrigued by the surprising, apparent esterification that occurred during detrityiation with aqueous acetic acid. When this presumed structural assignment (3) was unequivocally established (as described here) we found, as anticipated, that hexa-0-benzyltrehalose was directly convertible, in similar modest yield (27%), into the 6-monoacetate under the same conditions used for the detritylation of compound 1. We also have preliminary evidence that trehalose is similarly converted into a 6-monoacetate.
[This curious, but useful, transformation was in fact described by Duff nearly 30 years ago; glucose and galactose were preferentially acetylated at O-6 with 50% aqueous acetic acid for -24 h at 100" (yields of crude products -30%)6. It is evidently a little-known reaction, but because of the ease with which the products can be obtained, it may be worthy of resurrection from its present obscurity.]
Compound 3 serves as an ideal starting material for synthesis of 6-Omycoloyl-and 6-0-corynomycoloyl-trehalose, the isolation of which from various bacterial sources has been described'-". 6'-0-Acetyl-6-monomycolates have also