Synthetic studies toward Mycobacterium tuberculosis sulfolipid-I.
Sulfolipid-I (SL-I) is an abundant metabolite found in the cell wall of Mycobacterium tuberculosis that is comprised of a trehalose 2-sulfate core modified with four fatty acyl substituents. The correlation of its abundance with the virulence of clinical isolates suggests a role for SL-I in pathogenesis, although its biological functions remain unknown. Here we describe the synthesis of a SL-I analogue bearing unnatural lipid substituents. A key feature of the synthesis was application of an intramolecular aglycon delivery reaction to join two differentially protected glucose monomers, one prepared with a novel alpha-selective glycosylation. The route developed for the model compound can be readily extended to the synthesis of native SL-I as well as additional analogues for use in the investigation of SL-I's functions.
Leigh
Clifton D
CD
Department of Chemistry and Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
Bertozzi
Carolyn R
CR
D000215:Acylation; D005947:Glucose / Q000737:chemistry; D006017:Glycolipids / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D014199:Trehalose / Q000737:chemistry; D037521:Virulence Factors / Q000138:chemical synthesis* / Q000737:chemistry
D006017:Glycolipids; D037521:Virulence Factors; C009355:sulfolipid I; D014199:Trehalose; D005947:Glucose