Synthesis of 4,6:2',3':4',6'-tri-O-cyclohexylidene-alpha,alpha'-trehalose 2-palmitate: an intermediate for the synthesis of mycobacterial 2,3-di-O-acyl-alpha,alpha'-trehalose antigens.
The aim was to 'triprotect' trehalose by placing various acetals, or related protecting groups, across the 4,6-, 2',3'-, and 4',6'-positions, leaving the 2,3-positions free for subsequent acylation. Isopropylidene and ethylidene acetals were studied, with the formation of a small amount of 4,6:2',3':4',6'-tri-O-isopropylidene-alpha,alpha'-trehalose. 4,6:4',6'-Di-O-benzylidene-2',3'-O-(tetraphenyldisiloxane-1,3-d iyl)-alpha, alpha'-trehalose 2,3-diacetate was prepared in low yield. 1,1-Dimethoxycyclohexane reacted with methyl alpha-D-glucopyranoside to afford the 4,6-O-cyclohexylidene derivative, isolated as the diacetate; mild acid cleavage of the acetal gave the 2,3-diacetate. 4,6:2',3':4',6'-Tri-O-cyclohexylidene-alpha,alpha'-trehalose is the major product of the reaction between alpha,alpha'-trehalose and 1,1-dimethoxycyclohexane. 2,3:4,6:2',3':4',6'-Tetra-O-cyclohexylidene-, 4,6:4',6'-di-O-cyclohexylidene-, and 4,6-O-cyclohexylidene-alpha,alpha'-trehaloses were also isolated in lower yields, all acetals being characterised as their peracetates. The proportions of the different trehalose acetals were dependent upon the molar ratio of 1,1-dimethoxycyclohexane and particularly on the reaction temperature. The triprotected trehalose acetal was acylated with palmitic acid, with excellent regioselectivity, affording the 2-O-palmitoyl ester. This 2-monoacylated, triprotected trehalose is a key intermediate for the synthesis of 2,3-di-O-acyl-alpha,alpha'-trehalose glycolipid antigens, isolated from Mycobacterium fortuitum and Mycobacterium tuberculosis.
Wallace
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Department of Chemistry, University of Newcastle, United Kingdom.
Minnikin
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D000215:Acylation; D000942:Antigens, Bacterial / Q000737:chemistry*; D002240:Carbohydrate Sequence; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000276:immunology*; D014199:Trehalose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000276:immunology
D000942:Antigens, Bacterial; D014199:Trehalose