Total synthesis of the fully lipidated glycosylphosphatidylinositol (GPI) anchor of malarial parasite Plasmodium falciparum

We report a new and convergent strategy for the total synthesis of fully lipidated glycosylphosphatidylinositol (GPI) anchor, the major pro-inflammatory factor of malarial parasite (Plasmodium falciparum). The key features of our approach include, the access to the key glucosamine–inositol intermediate by a novel route without a priori resolution of myo-inositol, convergent assembly of the tetramannose glycan domain, flexibility for the placement of the three fatty acids in the desired order in the final steps, and the opportunity to construct GPI analogues/mimics to probe the biosynthesis, immunology and cell biology of the GPI anchor pathway in the malaria parasite.