合成路线1

O-Protection of gluconolactone (I) with TMSCl in the presence of NMM in THF yields the tetrasilylgluconolactone (II) , which by coupling with either 2-(5-bromo-2-methylbenzyl)-5-(4-fluorophenyl) thiophene (III), with previous treatment with BuLi in THF/toluene at –78 °C , or with iodobenzyl derivative (IV), with previous treatment with Me3SiCH2Li in THF at –40 °C or i-PrMg-Cl·LiCl in THF at 0 °C , provides the D-glucopyranose derivative (V) . Finally, D-glucopyranose (V) is desilylated and reduced stereospecifically by means of Et3SiH and BF3·Et2O in dichloroethane .
Alternatively, glucosidation and cleavage of the silyl protecting groups in intermediate (V) with MeOH and MsOH affords the methyl D-glucopyranoside derivative (VI) , which then undergoes enantiospecific reduction in the presence of TIPS or Et3SiH and BF3·Et2O .
Acetylation of the hydroxyl groups of the methyl D-glucopyranoside (VI) with Ac2O in the presence of NMM and DMAP in toluene/EtOAc leads to tetraacetate derivative (VII), which is then reduced by means of Et3SiH and BF3·Et2O in acetonitrile to give stereospecifically the Dglucitol derivative (X). Finally, glucitol (X) is hydrolyzed with LiOH·H2O in MeOH/THF or with NaOMe in refluxing MeOH and subsequently treated with AcOH .
D-Glucitol derivative (X) can also be prepared by treatment of iodobenzyl derivative (IV), with s-BuMgCl·LiCl in THF at 2 °C and addition of the resulting Grignard reagent to a solution of the tetraacetyl gluconolactone (VIII) in THF at –35 °C to give the D-glucopyranose derivative (IX), which then undergoes enantiospecific reduction by means of Et3SiH and BF3·Et2O or BF3·THF in acetonitrile or in the presence of AlCl3 and (Me2SiH)2O in acetonitrile .