1,2-Diacetals in Synthesis: Total Synthesis of a Glycosylphosphatidylinositol Anchor of Trypanosoma brucei

Abstract

A full account on a total synthesis of GPI anchor 1 employing butanediacetal (BDA) groups and a chiral bis(dihydropyran) is presented. The reactivity of selenium and thio glycosides was tuned by the use of BDA groups. This allowed the assembly of an appropriately protected GPI anchor precursor 2 in just six steps from the six building blocks 5-10 including only one protecting group manipulation (see Scheme 1). myo-Inositol was desymmetrised with the bis(dihydropyran) derivative 15 and appropriately protected to give inositol acceptor 21 in nine steps and 17 % overall yield (see Scheme 3). The use of common starting materials and BDA-protections give efficient access to building blocks 5, 6, 7 and 8 (see Scheme 5). A new and improved synthesis of the glucosamine donor 28 is included. In summary, a highly convergent and efficient synthesis of GPI anchor 1, which is clearly adaptable to other GPI anchors, has been reported.