title: An improved synthesis of trehalose 6-mono- and 6,6'-di-corynomycolates and related esters.
abstract: A simplified synthesis of 6-mono- and 6,6'-di-corynomycolate esters of alpha,alpha-trehalose, and related compounds, was achieved by coupling the (hydroxyl-protected) acids to the partially trimethylsilylated sugar in the presence of dicyclohexylcarbodiimide and 4-dimethylaminopyridine. As acid reactants, (2-RS,3-RS)-3-hydroxy-2-tetradecyloctadecanoic acid (DL-corynomycolic acid) and its 2RS,3SR diastereomer were prepared from methyl palmitate by sequential Claisen condensation, reduction, chromatographic separation, and saponification. Reaction with tert-butylchlorodimethylsilane (imidazole) gave the disubstituted ether-esters, which were converted into the required 3-tert-butyldimethylsilyl ethers by partial hydrolysis. 6-Linked monocorynomycolate was obtained in excellent yield (78%) from the reaction of the RS,SR acid with the known heptakis-O-(trimethylsilyl)trehalose, and in good yield from equimolar portions of RS,RS acid and hexakis-O-(trimethylsilyl)trehalose. An excess (2.5-molar portions) of the RS,RS acid gave the 6,6'-diester (69%). The mono- and di-palmitate were similarly obtained from (Me3Si)6-trehalose. The mono (RS,RS)-(Me3Si)6-trehalose coupling product was partially resolved on a silica gel column into its RR and SS diastereomers, the former corresponding to the naturally occurring trehalose monocorynomycolate. All coupling products were deprotected to free trehalose esters by treatment first with K2CO3 in methanol, then tetrabutylammonium fluoride-trifluoracetic acid in oxolane.
authors.affiliation: Mycobacteriology Research Laboratory, William S. Middleton Memorial Veterans Administration Hospital, Madison, WI 53705.
authors.forename: A K
authors.initials: AK
authors.lastname: Datta
authors.forename: K
authors.initials: K
authors.lastname: Takayama
authors.forename: M A
authors.initials: MA
authors.lastname: Nashed
authors.forename: L
authors.initials: L
authors.lastname: Anderson
mesh_terms: D002240:Carbohydrate Sequence; D003311:Cord Factors / Q000138:chemical synthesis*; D004952:Esters / Q000138:chemical synthesis; D008969:Molecular Sequence Data; D009171:Mycolic Acids / Q000737:chemistry*
chemical_list: D003311:Cord Factors; D004952:Esters; D009171:Mycolic Acids; C021099:trehalose monomycolate; C013898:corynomycolic acid