SYNTHESIS OF NEW ACYCLIC NUCLEOSIDES

The preparation of 1-(4,5-dihydroxypentyl)uracils and the correspondin g cytosine derivatives as acyclic analogs of 3'-deoxythymidine and 2', 3'-dideoxycytidine (DDC), respectively, is described. The synthesis co nsists of alkylation of sodium salts of pyrimidine bases with 4-penten yl p-toluenesulfonate 2 followed by oxidation of the double bond with peroxyformic acid to afford the 1-(4,5-dihydroxypently)uracils. 1-(4,5 -Dihydroxypentyl)uracil was further reacted to give the corresponding cytosine derivatives via the 4-(1,2,4-triazol-1-yl) derivative. 1-(5-h ydroxy-4-methoxypentyl)uracil (9a) was obtained together with the 4-hy droxy-5-methoxypentyl derivative 9b from 1-(4-pentenyl)uracil (3b) by epoxidation and subsequent acid-catalyzed cleavage of the epoxide by m ethanol. 6-(Thymin-1-yl) and 6-(cytosin-1-yl) derivatives of (Z)-2,3,6 -trideoxy-D-erythro-2-hexenitol 17a,c were synthesized by alkylation o f the sodium salts of thymine and N4-isobutyrylcytosine with 3,4-di-O- acetyl-6-O-p-toluenesulfonyl-D-glucal (14) followed by hydrolysis, red uction with sodium borohydride and deprotection.