CuSO4/KI As Catalyst for the Synthesis of 1,4-Disubstituted-1,2,3-Triazolo-Nucleosides.

A simple and inexpensive procedure has been developed for the selective formation of 1,4-disubstituted-1,2,3-triazolo-nucleosides starting from organic azides and terminal alkynes, mediated by in situ generated copper(I) catalyst from readily available CuSO4 and KI.

Synthesis and biological evaluation of some alpha-[6-(1'-carbamoylalkylthio)-1 H-pyrazolo[3,4-D]pyrimidin-4-yl]thioalkylcarboxamide acyclonucleosides.

The reaction of 1H-pyrazolo[3,4-d]pyrimidin-4,6-dithione 11 with compounds 12a-c produces ethyl alpha-[6-(1'-carboethoxyalkylthio)-1 H-pyrazolo[3,4-d]pyrimidin-4-yl]thioalkylates 13a-c, respectively. These heterocycles were alkylated, separately, with alkylating agents 14, 15, and 16 to afford, predominately, the N(1)-acyclic nucleosides (17-19)a-c, which were deprotected to give the desired products (20-22)a-c. All synthetic compounds were characterized on the basis of their physical and spectroscopic properties.

Synthesis and antiviral activity of some C2-, C4-, and C6-substituted pyrazolo[3,4-D]pyrimidine acyclonucleosides with the alkylating chains of ACV, HBG, and ISO-DHPG.

A useful route to obtain trisubstituted pyrazolo[3,4-d]pyrimidines 14-17 is described. Those later were coupled with the alkylating agents 18-20 as in ACV, HBG, and iso-DHPG to give, after deprotection, the desired acylonucleosides 33-44. Almost all of the new compounds were evaluated for their inhibitory effects against the replication of various DNA viruses in culture.

Synthesis and biological activity of some unsaturated 6-azauracil acyclonucleosides.

A useful route is described for obtaining Z and E unsaturated alkylating agents 3 and 4. Coupling 6-azauracils 5 and 6 with unsaturated alkylating agent followed by the deprotection with H+ resin gave acyclonucleosides 11-14 in good overall yields. Unsaturated acyclonucleosides phosphonates 19 and 20 were prepared using potassium carbonate as base and 4-bromobut-2-enyl diethyl phosphonate 16 as the alkylating agent.

Synthesis and biological activity of some 4-substituted 1-[1-(2,3-dihydroxy-1-propoxy)methyl-1,2,3-triazol-(4 & 5)-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidines.

Cycloaddition of 7a, b with 6 gave, after separation and deprotection, two regioisomers 10a, b and 11a, b. The deprotected acyclic nucleoside 10a used as the precursor for the preparation of 4-amino (12), 4-methylamino (13), 4-benzylamino (14), 4-methoxy (15) and 4-hydroxy (16) analogues. All acyclic nucleosides were evaluated for their inhibitory effects against HIV-1(IIIB), HIV-2(ROD) in MT-4 cells, for their anti-tumor activity and for their inhibitory effects against Mycobacterium tuberculosis.