Processes for preparing 1,3-dioxolane nucleosides

A process for preparing a D- or L-dioxolane nucleoside of formulae III-VI:

• wherein
• R is H, halogen, OH, OR′, SH, SR′, NH2, NHR′, NR′2, lower alkyl of C1-C4, CH═CH2, N3C═CH2, CO2H, CO2R′, CONH2, CN, CONHR′, CH2OH, CH2CN, CH2CH2OH, CF3, CH2CH2F, CH═CHCO2H, CH═CHCO2R′, CH═CHCl, CH═CHBr, or CH═CHI;
• R′ is lower alkyl (C1-C4);
• each X and Y is independently H, halogen, OH, OCH3, SH, SCH3, NH2, NHR′, NR′2, or CH3;
• and
• Z is CH, or C—X;
• comprising the steps of:
• 1) preparing compounds of formula VII or VIII:
• by:
• a) oxidation of 1,2-O-protected-glycerol to an acid salt, or hydrolysis of methyl (R)- or (S)-1,2-O-protected-glycerate to form intermediate 1:
• b) alkylation of intermediate 1 with a compound of formula X′CH2CH(OR6)2, wherein X′ is halogen or pseudohalogen, and R6 is alkyl or aralkyl (C1-20);
• c) cyclization with an acid catalyst optionally with hydrolysis of the acetal;
• 2) hydrolyzing the ester group of the compound of formula VII or VIII followed by protection of the resulting alcohol under basic conditions to form a compound of formula 6 (including D- and L-isomers):
• wherein R7 is a protecting group;
• 3) decarboxylating the carboxylic group of compound 6;
• and
• 4) coupling with a purine or pyrimidine base or its derivative, followed by deprotection to form a D- and L-dioxolane nucleoside of formulae III-VI.