Total synthesis of phosphatidylinositol mannosides of Mycobacterium tuberculosis.
The total synthesis of phosphatidylinositol mannosides (PIMs), a key class of antigenic glycolipids found on the cell wall of Mycobacterium tuberculosis, is described. The synthetic strategy relied on a [4 + 3] glycosylation of tetramannoside 1 and pseudotrisaccharide 2, which allowed for convergent access to the glycan backbone of the phosphatidylinositol dimannoside (PIM2) and hexamannoside (PIM6). A short practical synthesis of tuberculostearic acid was achieved based on a copper-catalyzed cross-coupling reaction. Union of the glycan and lipid parts resulted in the first total synthesis of native PIM2 and PIM6.
Laboratory for Organic Chemistry, Swiss Federal Institute of Technology (ETH) Zürich Wolfgang-Pauli-Str. 10, HCI F315, 8093 Zürich, Switzerland.
Xinyu
X
Liu
Bridget L
BL
Stocker
Peter H
PH
Seeberger
D002240:Carbohydrate Sequence; D006031:Glycosylation; D008358:Mannose / Q000737:chemistry; D008362:Mannosides / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000138:chemical synthesis*
D008362:Mannosides; D010716:Phosphatidylinositols; C034154:phosphatidylinositol mannoside; D008358:Mannose