Total synthesis, from D-xylose, of chiral, ring-contracted 1D-myo-inositol 1,4,5-trisphosphate and 1,3,4,5-tetrakisphosphate analogues with C-2 excised

Abstract

A route to chiral, cyclopentane-based congeners of the second messenger 1D-myo-inositol 1,4,5-trisphosphate and its enigmatic metabolite 1D-myo-inositol 1,3,4,5-tetrakisphosphate, starting from D-xylose, is described. Reaction of allyl α-D-xylopyranoside 7 with 2,2,3,3-tetramethoxybutane gave a 1∶1 mixture of the 2,3- and 3,4-butanediacetal-protected derivatives 8 and 9. The latter was converted in four steps into 2-O-benzyl-3,4-bis-O-(p-methoxybenzyl)-D-xylopyranose 15, which on reduction with sodium borohydride gave 2-O-benzyl-3,4-bis-O-(p-methoxybenzyl)-D-xylitol 16. Swern oxidation followed by samarium(II) iodide-mediated pinacol coupling gave a 1∶3 mixture of 1L-1,2,3,4/5-1-benzyloxy-2,3-dihydroxy-4,5-bis-(p-methoxybenzyloxy)cyclopentane 18 and 1L-1,2,4/3,5-3-benzyloxy-1,2-dihydroxy-4,5-bis-(p-methoxybenzyloxy)cyclopentane 19. The identity of the latter was confirmed by conversion into known compounds, and further elaboration gave the target compounds, 1D-1,2,4/3,5-cyclopentanepentaol 1,3,4-trisphosphate 5 and 1D-1,2,4/3,5-cyclopentanepentaol-1,2,3,4-tetrakisphosphate 6.