US EPA

1203834 

Journal Article 

SYNTHESIS OF NEW ACYCLIC NUCLEOSIDES 

Schou, C; Pedersen, EB; Nielsen, C 

1993 

Yes 

Acta Chemica Scandinavica
ISSN: 0904-213X
EISSN: 1902-3103 

47 

9 

889-895 

10.3891/acta.chem.scand.47-0889 

WOS:A1993LX76300008 

The preparation of 1-(4,5-dihydroxypentyl)uracils and the corresponding cytosine derivatives as acyclic analogs of 3'-deoxythymidine and 2',3'-dideoxycytidine (DDC), respectively, is described. The synthesis consists of alkylation of sodium salts of pyrimidine bases with 4-pentenyl 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-hydroxy-4-methoxypentyl)uracil (9a) was obtained together with the 4-hydroxy-5-methoxypentyl derivative 9b from 1-(4-pentenyl)uracil (3b) by epoxidation and subsequent acid-catalyzed cleavage of the epoxide by methanol. 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 of the sodium salts of thymine and N4-isobutyrylcytosine with 3,4-di-O-acetyl-6-O-p-toluenesulfonyl-D-glucal (14) followed by hydrolysis, reduction with sodium borohydride and deprotection.