J. L. Barascut

SYNTHESIS AND ANTI-HIV ACTIVITY OF NEW MODIFIED 1,2,3-TRIAZOLE ACYCLONUCLEOSIDES

The synthesis of 1,2,3-triazole acyclonucleosides 7a-h via 1,3-dipolar cycloaddition of N-9/N-1-propargylpurine/pyrimidine 2a-h with azido-pseudo-sugar 4 is described and none of them had anti-HIV activity.

Synthesis of (Z) and (E) α-alkenyl phosphonic acid derivatives of purines and pyrimidines

Abstract (Z) and (E)-2-(purin-9-yl/ pyrimidin-1-yl)ethylen-1-ylphosphonic acid 10–18 were synthetized by Michael addition of heterocyclic base with the diethylethynylphosphonate and deprotection of the acyclic nucleoside phosphonate with bromotrimethylsilane.

Efficient Synthesis of 4-Thio-D-ribofuranose and Some 4′-Thioribonucleosides

Abstract A synthetic pathway to reach easily the 4-thio-D-ribofuranose is described. Some corresponding pyrimidine α and β 4′-thioribonucleosides have been synthesized and evaluated as antiviral agents against various viruses.

Synthesis of new acyclic nucleoside phosphonic acids by Michael addition

Abstract New acyclic nucleoside phosphonic acids in the purine and pyrimidine series were prepared via one step by Michael addition. These compounds are the first reported acyclonucleosides enamines which incorporate the α, β-unsaturated phosphonic acid as a phosphate mimic.

SYNTHESIS AND BIOLOGICAL ACTIVITY OF 4-SUBSTITUTED 1-[1-(2-HYDROXYETHOXY)- METHYL-1,2,3-TRIAZOL-(4 & 5)-YLMETHYL]-1H-PYRAZOLO[3,4-d]PYRIMIDINES

The chemical synthesis of some 4-substituted 1-[1-(2-hydroxyethoxy)methyl-1,2,3-triazol-(4 and 5)-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidines 12a,b, 13a,b and 14–23 as acyclic nucleosides is described. Treatment of (2-acetoxyethoxy)methylbromide with sodium azide afforded (2-acetoxyethoxy)methylazide 9. The heterocycles 6a,b were alkylated, separately, with propargyl bromide to obtain, regioselectively, 4-(methyl and benzyl)thio-1-(prop-2-ynyl)-1H-pyrazolo[3,4-d]pyrimidines 7a,b. These N1-alkylated products were condensed with compound 9 via a 1,3-dipolar cycloaddition reaction to obtain, after separation and deprotection, 1,4 and 1,5-regioisomers 12a,b and 13a,b. The deprotected acyclic nucleosides 12a and 13a served as precursors for the preparation of 4-amino (14 and 15), 4-methylamino (16 and 17), 4-benzylamino (18 and 19), 4-methoxy (20 and 21) and 4-hydroxy (22 and 23) analogues. Compounds 7a,b and all deprotected acyclic nucleosides were evaluated for their inhibitory effects against the replication of HIV-1(IIIB) and HIV-2(ROD) in MT-4 cells and for their anti-tumor activity. No marked activity was found. However, initial evaluation of 6a,b, 7a,b, 12a,b, 13a,b and 14–23 showed that compound 7b has marked activity against M. tuberculosis.

Synthesis of 3′-Deoxy-3′-[4-(pyrimidin-1-yl)methyl-1,2,3-triazol-1-yl]thymidine via 1,3-Dipolar Cycloaddition

Abstract The synthesis of new 3′-deoxy-3′-[4-(pyrimidin-1-yl)methyl-1,2,3-triazol-1-yl]thymidine 6a–f, from 3′-azido-3′-deoxy-5′-O-monomethoxytrityl-thymidine is described. The key step is the 1,3-dipolar cycloaddition between the azido group of the protected AZT 3 and N-1-propargylpyrimidine derivatives 2a–f. All new derivatives 6a–f were evaluated for their inhibitory effects against the replication of HIV-1 (IIIB), HIV-2 (ROD). No marked activity was found.

Synthesis of New 1,2,3-Triazole Acyclonucleoside Analogues of ACV and HBG

Abstract 1,3-dipolar cycloaddition of. N-9/N-1-propargylpurine/pyrimidine to the corresponding azido-compounds 9–10 produces acyclonucleoside analogues 13a-h, 14a-h in which the 4-methyl-1,2,3-triazole is used as spacer arm.

Synthesis of 3′-Deoxy-3′ and 5′-Deoxy-5′-[4-(Purin-9-yl/Pyrimidin-1-yl) methyl-1,2,3-Triazol-1-yl]thymidine via 1,3-Dipolar Cycloaddition

Abstract Synthesis of new 3′-deoxy-3′ and 5′-deoxy-5′-[(4-(purin-9-yl/pyrimidin-1-yl)methyl-1,2,3-Triazol-1-yl]thymidine 8a-g 10a-g from 3′-azido-3′-deoxy-5′-O-monomethoxytrityl-thymidine and 5′-azido-5′deoxythymidine respectively are described. The key step is the 1,3-dipolar cycloaddition between the azido group and N-9/N-1-propargylpurine/pyrimidine derivatives.

4′-Thio-β-D-oligoribonucleotides: Nuclease Resistance and Hydrogen Bonding Properties

Abstract The syntheses and the study of nuclease resistance and hydrogen bonding of modified oligoribonucleotides, i.e. 4′-thio-β-D-oligoribonucleotides (4′-S-RNA), are reported.

Synthesis and biological activities of (Z) and (E) alpha-ethenyl acyclonucleosides

Synthesis of Z and E ethenyl acyclonucleosides (6a-e and 7a-e) via Michael addition of nucleobases with the diethyl acetylenedicarboxylate is described. The structures of compounds have been confirmed by spectral data. New compounds were found to be inactive against DNA and RNA viruses.