Synthesis of a Complex Glycolipid from Malassezia Pachydermitis Permits Identification of Ability to Signal through Human Mincle

Session: 
PS2 Poster session 2 Even numbers
Code: 
P230
Location (hall): 
Foyer
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15
Phillip
van der
Peet

Phillip van der Peet1, Spencer Williams1, Christian Gunawan1, Miyuki Watanabe2, Sho Yamasaki2,3

1School of Chemistry and Bio21 Institute, University of Melbourne, Parkville, Australia, 2Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3Department of Molecular Immunology, Immunology Frontier Research Center, Osaka University

Malassezia pachydermitis is a commensal fungus that causes skin diseases and otitis in humans and carnivorous pets and can result in serious infections in susceptible humans. Yamasaki and co-workers isolated a unique glycolipid, 44-2, from M. pachydermitis composed of a mannitol core bearing three β-mannosylated hydroxystearate chains. Glycolipid 44-2 was shown to be a potent stimulator of murine macrophage-inducible C-type lectin (Mincle) receptor,[1] a pattern recognition receptor of the innate immune system that senses lipidic species and signals the presence of bacteria and fungi. Glycolipid 44-2 contains three β-mannosyl linkages to 10-hydroxystearic acid moieties, which are in turn esterified to L-mannitol. We report the concise synthesis of this complex lipid through a highly convergent approach utilising a single glucosyl trichloroacetimidate donor to generate all four β-glycosidic linkages. Inversion of glucose at C2 was used to access the synthetically challenging β-mannosyl configuration. The chiral 10-hydroxystearic acid chains were generated by cuprate coupling to an enantiopure epoxide obtained by Jacobsen’s hydrolytic kinetic resolution of the racemate. Synthetic 44-2 was shown to be a potent agonist of signalling through human Mincle, and represents the first such fungal metabolite to do so.

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