Aliphatic analogues of nucleotides: synthesis and affinity towards nucleases

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Abstract
DL-1-(2,3-Dihydroxypropyl) thymine waa prepared by Hilbert-Johns on reaction of 2,4-dimethoxy-5-methylpyrimidine with allyl bromide followed by the osmium tetroxide catalyzed hydroxyltion of the l-allyl-4-methoxy-5-methylpyrimidin-2-one obtained as an intermediate. The D-glycero enantiomer, R-1-(2,3-dihydroxypropyl) thymine and the corresponding 1-substituted uracil derivative were prepared from 3-O-p-toluenesulfonyl-1,2-O-isopropylidene-D-glycerine and sodium salt of 4-methoxy-5-methylpyrimidin- 2-one or 4-methoxypyrimidin-2-one followed by treatment with hydrogen chloride in ethanol. The phosphorylation of tht above 2,3-dihydroxypropyl derivatives with phosphoryl chloride in triethyl phosphate afforded the corresponding 3-phosphates which were transformed into the 2′,3′-cyclic phosphates by the condensation with N, N-dieyclohexylcarbodiimide. The latter compounds of the D-glycero configuration are split by some microbial RNases to the 3-phosphates.