METHOD OF SYNTHESIS 2'-DEOXYXYLOTHYMIDINE, DERIVATIVES OF D-XYLOFURANOSE, DERIVATIVES OF XYLOTHYMIDINE

摘要

FIELD: organic chemistry, biochemistry. SUBSTANCE: invention relates to method of synthesis of 2'-deoxyxylothymidine, derivatives of D-xylofuranose and derivatives of 2'-deoxyxylothymidine that can be used as the parent and intermediate compounds for synthesis of 3'-azido-2',3'-dideoxythymidine (azidothymidine) - an effective drug against AIDS and for synthesis of 5'-phosphonate-3'-azido-2', 3'-dideoxythymidine also. Method of synthesis of 2'-deoxyxylothymidine involves treatment of D-xylose with acetone in the presence of concentrated sulfuric acid, treatment of obtained compound (3) with p-toluyl chloride in the presence of pyridine with formation of compound (4); removing the protective 1,2-O-isopropylidene group by action on compound of the formula (4) with mineral acid solution with formation of compound of the formula (5); acetylation of compound (5) by its treatment with acetic anhydride in acetic acid medium in the presence of nucleophilic catalyst or by its treatment with acetic anhydride or acetyl halide in pyridine with formation of compound of the formula (6); reaction of compound (6) with thymine derivative of the formula (7) with formation of compound of the formula (8); selective hydrolysis of 2'-acetate in compound (8) by its treatment with ammonia alcoholic diluted solution with formation of compound of the formula (9); treatment of compound (9) with methane sulfochloride or p-toluene sulfochloride with formation of 2-mesylate of the formula (10) or 2'-tosylate of the formula (10a); treatment of compound (10) or (10a) with sodium or potassium hydrocarbonate in organic solvent with formation of 2,2'-anhydro-compound of the formula (11); interaction of compound (11) with reagent that is used for replacement of hydroxyl group for bromine atom with formation of compound of the formula (12); reduction of compound (12) with formation of compound of the formula (13); removing 3- and 5-p-toluylic protective groups in compound (13). Compounds of the formula (A): where Tol-p - toluylic protective group p--CH₃-C₆H₄--C(O)-; R₃ and R₄ together form one propylidene protective group, or R₃ = R₄ - hydrogen. Compounds of the general formula (B): where X means oxo-group and Y - aceto-group, or Y - hydroxyl group, or Y - mesyl (or p-tosyl) group. Proposed compounds can be used as intermediate compounds for synthesis of 3'-azido-2',3'-dideoxythymidine or 5'-phosphonate-3'-azido-2',3'-dideoxythymidine. EFFECT: improved method of synthesis. 3 cl, 6 dwg