2 research outputs found
Synthesis and substrate properties towards HIV-1 reverse transcriptase of new diphosphate analogues of 9-[(2-phosphonomethoxy)ethyl]adenine
[Synthesis, Structure and Some Biochemical-properties of 3'-branched Thymidines and Their 5'-phosphate Derivatives]
A full scheme of synthesizing 3'-C-methyl-2'-deoxynucleosides and 3'-C-methylidene-28,3'-dideoxythymidine has been developed by using 2-deoxyribose. The stereoselectivity of the Grignard reagent's attachment to 2-deoxyfuranose 3-ulosides determined by the substitute configuration at Cl and the condensation stereoselectivity of 3-C-methyl-2-deoxyfuranosides with silylated thymine dependent on the configuration of the hydroxyl or-OBz group at C3 have been studied. The structure of the resultant compounds has been evidenced by H-1 and C-13 NMR, UV spectroscopies and C, H, and N analysis. The C2'-endo-C1-exo-conformation, the anti-conformation of the thymine base in relation to the glycoside bond and the gosh+-conformation in relation to the C4'-C5' bond are characteristic of the structure of 3'-C-methyl-2'-deoxythymidine in the crystal. 3'-C-Metyl-2'-deoxythymidine-5'-triphosphate exhibited the properties of the competitive inhibitor against 2'-deoxythimidine 5'-triphosphate in the synthesis of DNA catalyzed by various DNA-polymerases and reverse transcriptases. But none of these enzymes incorporated this compound into the growing DNA chain. At the same time 3'-C-methylidene-2',3'-dideoxythymidine-5'-triphosphate was incorporated into the 3'-end of the chain of DNA catalyzed by HIV reverse transcriptase, though the latter having a low efficacy. 3'-C-Methyl-2'-deoxythymidine failed to suppress HIV-1 production in the cultured MT-4 cells, its 5'-phosphite exhibiting a low activity under the same conditions