Study On The Synthesis Of L-Ribose With Chemical Method

Withα-D-glucose as starting material, L-ribose was synthesized by nine step reactions such as acetone protection, PDC (pyridinium dichromate) oxidation-NaBH4 reduction, acid selective hydrolysis, NaIO4 oxidative degradation, aldehyde group protection with methoxyl amine, DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) thorough hydrolysis- NaBH4 reduction and deoximation with titanium trichloride .Particularly, PDC oxidation method, NaIO4 oxidative degradation method and aldehyde group protection with methoxyl amine method were studied intensively. The hydroxyl group protecting reactions ofα-D-gluofuranose was studied. The isopropylidenation reaction ofα-D-gluofuranose was carried to synthesis 1,2:5,6-O-diisopropylidene-α-D-gluofuranose (2) with acetone-conc. H2SO4 system, by crystallization, the yield was 38%. Hydroxyl group stereo structure conversion in sugar was studied. The C-3 position hydroxyl group stereo structure of 2 was converted by PDC-Ac2O-CH2Cl2 oxidation and NaBH4 reduction, Thus 1,2:5,6-O-diisopropylidene-α-D-allofuranose (3) was synthesized, two steps overall yield was 70%. The preparation method of PDC was studied.Selective hydrolysis reaction ofα-D-allofuranose derivative 3 was studied. The selective hydrolysis reaction of 3 was carried to synthesize 1,2-O-isopropylidene-α-D-allofuranose (4) with dilute H2SO4–CH3OH, the yield was 92.2%. Oxidative degradation reaction of 4 was studied. The hydrolysis product 4 was carbon-decreasing oxidated with NaIO4-NaHCO3-H2O system. Thus 1,2-O-isopropylidene-α-D-ribo-pentodialdo-1,4-furanose (5) was synthesized , the yield was 86.9%. Aldehyde group protection reaction ofα-D-ribose derivative 5 was studied. The reaction was carried out with NH2OH-CH3OH system, CH3CH2SH-HCl system and NH2OCH3- CH3OH system. The methoxyl amine was determined as aldehyde group protection reagent. Thus 1,2-O-isopropylidene-α-D-ribo- pentodialdo-1,4-furanose-O-methyl-oxime (6c) was synthesized, the yield was 73.6%.Thorough hydrolysis- reduction reaction of 6c was studied. The diversion was converted by DDQ-CH3CN thorough hydrolysis and NaBH4 reduction. Thus L-ribose-O-methyl-oxime (7c) was synthesized, two steps overall yield was 79%. Deoximation reaction of the oxime 7c was studied premilinarily. The reaction of 7c was carried out to synthesize L-ribose (8) with TiCl3-THF system, the yield was 23.9%. Nine steps overall yield was 2.9%. Except the final step, no column chromatography separating method was applied in each step in all nine steps, Each step product was characterized with 1H-NMR.