[Synthesis and antimetabolite properties of 5-substituted 2'-deoxyuridines. Anomeric 5-(2-aminohexafluoroprop-2-yl)- and 5-(2-trifluoroacetylaminohexafluoroprop-2-yl)-2'-deoxyuridine].
Alkylation of 2,4-bis-O-(trimethylsilyl)uracil with hexafluoroacetone trifluoroacetylimine gave 5-(2-trifluoroacelylaminohexafluoroprop-2-yl)uracil, which was transformed by alkaline hydrolysis to 5-(2-aminohexafluoroprop-2-yl)uracil. The latter was glycosytated with 2-deoxy-3,5-di-O-p-toluoyl-alpha-D-ribofyranosyl chloride by means of various modifications of the silyl method leading to the predominant formation of beta-deoxynucleoside; after deacylation 1-(2-deoxy-beta-D-ribofuranosyl)-5-(2-aminohexafluoroprop-2-yl)ura cil was obtained. Interaction of silylated 5-(2-trifluoroacetylaminohexafluoroprop-2-yl)uracil with acylgalogenose gave anomeric O-substitutet deoxynucleosides, which were deblocked to give 5-(2-trifluoroacetylaminohexafluoroprop-2-yl)-2'-deoxyuridine and corresponding alpha-anomer. Alkaline hydrolysis of N-trifluoroacetyl group in both individual anomers produced 1-(2-deoxy-alpha-D-ribofuranosyl)-5-(2-aminohexafluoroprop-2-yl)ur acil and the abovementioned beta-anomer. Of all compounds synthesised only 1-(2-deoxy-beta-D-ribofuranosyl)-5-(2-aminohexafluoroprop-2-yl)ura cil has a moderate inhibitory effect on replication of vaccinia virus in vitro.
Mel'nik
S Ia
SIa
Bakhmedova
A A
AA
Iartseva
I V
IV
Kochetkova
M V
MV
Preobrazhenskaia
M N
MN
D000478:Alkylation; D000963:Antimetabolites / Q000138:chemical synthesis*; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005466:Fluorocarbons
D000963:Antimetabolites; D000964:Antimetabolites, Antineoplastic; D000998:Antiviral Agents; D003857:Deoxyuridine; C054045:5-(2-aminohexafluoroprop-2-yl)-2'-deoxyuridine; D005466:Fluorocarbons; C054046:5-(2-trifluoroacetylaminohexafluoroprop-2-yl)-2'-deoxyuridine
Sintez i antimetabolitnye svoĭstva 5-zameshchennykh 2'-dezoksiuridinov. Anomernye 5-(2-aminogeksaftorprop-2-il)- i 5-(2-triftoratsetilaminogeksaftorprop-2-il)-2'-dezoksiuridiny.