Stereocontrolled homologation of 1,2 : 3,4-di-O-isopropylidene-α-D-galacto-hexodialdo-1,5-pyranose to 7-deoxynonodialdose epimers via thiazole-aldehyde synthesis

Abstract

The three-carbon chain elongation of the title dialdose has been carried out by two approaches employing thiazole-based reagents: (i) aldol condensation with the lithium enolate of 2-acetylthiazole; (ii) olefination with triphenyl(thiazol-2-ylcarbonylmethylene)phosphorane and 1, 4-addition of benzyl oxide anion to the resultant vinyl ketone. The stereoselective reduction of the resultant (R) and (S)β-hydroxy ketones, followed by protection of the hydroxy groups as benzyl ethers, afforded four compounds consisting of the galactopyranosyl ring substituted at C-5 with stereoisomeric 1,3-bis(benzyloxy)propyl units bearing the thiazol-2-yl ring at the terminus of the chain. The unmasking of the formyl group from the thiazolyl ring to give 7-deoxynonodialdoses was carried out in two cases. The unequivocal assignment of the structures of two intermediates isolated in each route was established by X-ray room-temperature crystal-structure analyses.