Synthesis of some second-generation substrate analogues of early intermediates in the biosynthetic pathway of glycosylphosphatidylinositol membrane anchors

1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-octyl-myo-inositol 1-( 1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (23) and the corresponding 2 -O-hexadecyl-D-myo-inositol compound 24 have been prepared as substrate ana logues of an early intermediate in the biosynthetic pathway of glycosylphos phatidylinositol (GPI) membrane anchors. 1-D-6-O-(2-Amino-2-deoxy-alpha-D-g lucopyranosyl)-myo-inositol 1-(1,2-di-O-octyl-sn-glycerol 3-phosphate) has also been prepared as a substrate analogue. Biological evaluation of the an alogues 23 and 24 revealed that they are neither substrates nor inhibitors of GPI biosynthetic enzymes in the human (HeLa) cell-free system but are po tent inhibitors at different stages of GPI biosynthesis in the Trypanosoma brucei cell-free system. (C) 1999 Elsevier Science Ltd. All rights reserved .