Chemical Synthesis and Immunosuppressive Activity of Dipalmitoyl Phosphatidylinositol Hexamannoside

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• 作者：Gary D. Ainge ; Benjamin J. Compton ; Colin M. Hayman ; William John Martin ; Steven M. Toms ; David S. Larsen ; Jacquie L. Harper ; Gavin F. Painter
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：June 17, 2011
• 年：2011
• 卷：76
• 期：12
• 页码：4941-4951
• 全文大小：1063K
• 年卷期：v.76,no.12(June 17, 2011)
• ISSN：1520-6904

文摘

Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of phosphoglycolipids with significant immune-modulating properties. We present here the synthesis of dipalmitoyl phosphatidylinositol hexamannoside (PIM₆) 1 and the first reported functional biology of a synthetic PIM₆. Key steps in the synthetic protocol included the selective glycosylation of an inositol 2,6-diol with a suitably protected mannosyl donor and construction of the glycan core utilizing a [3 + 4] thio-glycosylation strategy. The target 1 was purified by reverse phase chromatography and characterized by standard spectroscopic methods, HPLC, and chemical modification by deacylation to dPIM₆. The ¹H NMR spectrum of synthetic dPIM₆ obtained from 1 matched that of dPIM₆ obtained from nature. PIM₆ (1) exhibited dendritic cell-dependent suppression of CD8⁺ T cell expansion in a human mixed lymphocyte reaction consistent with the well established immunosuppressive activity of whole mycobacteria.