Synthesis of d- and l- myo-inositol 2,4,5-trisphosphate and trisphosphorothioate: structural analogues of d- myo-inositol 1,4,5-trisphosphate

Abstract

The preparation of d- and l- myo-inositol 2,4,5-trisphosphate is described, together with the phosphorothioate counterparts. The known chiral diols d- and l-1,4-di- O-benzyl-5,6-bis- O- p-methoxybenzyl- myo-inositol were regioselectively protected at the 3-position using a benzyl group via a 2,3- O-stannylene acetal. Removal of the p-methoxybenzyl groups of each enantiomer gave d- and l-1,3,6-tri- O-benzyl- myo-inositol. Phosphitylation with bis(benzyloxy)diisoproplyaminophosphine and 1 H-tetrazole gave the trisphosphite intermediate for each enantiomer. Oxidation with 3-chloroperoxybenzoic acid gave the fully protected d- and l- myo-inositol 2,4,5-trisphosphates. Sulphoxidation of the d- and l-2,4,5-trisphosphite intermediates gave the fully protected d- and l- myo-inositol 2,4,5-trisphosphorothioate compounds. The fully protected trisphosphates were deblocked using hydrogenolysis and the phosphorothioates were deprotected using sodium in liquid ammonia. The individual compounds were then purified using ion exchange chromatography to afford pure d- and l- myo-inositol 2,4,5-trisphosphates together with the corresponding phosphorothioates.