Amino acid derivatives, part 4: synthesis and anti-HIV activity of new naphthalene derivatives.

A new series of 2-(naphthalen-2-yloxy)-N-[(aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl] acetamides 5a-f was synthesized from naphthalene-derived glycine derivative 2 via the hydrazinoacetamide analogs 4a-f. Alternatively, treatment of 4a with H(2)SO(4) afforded 2-(naphthalen-2-yloxy)-N-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)methyl) acetamide 6a. Alkylation or sulphonylation of 5a afforded the S-alkylated derivatives 7 and 8, respectively.

New acyclic quinoxaline nucleosides. Synthesis and anti-hiv activity.

A series of acyclonucleosides substituted 1-(4,5-dihydroxypentyl) (13-8) and 2-(4,5-dihydroxypentyloxy)quinoxalines (19-24) were synthesized by the sharpless asymmetric dihydroxylation of the derivatives 1-6 and 7-12, respectively. Treatment of the quinoxaline base 26 with (R)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl-p-toluenesulfonate (27) in the presence of NaH/DMF furnished 28. Acid hydrolysis of 28 gave 1-(2,3-dihydroxypropyl)-6,7-dimethyl-quinoxaline-2-one (29).

Amino acid derivatives. Part I. Synthesis, antiviral and antitumor evaluation of new alpha-amino acid esters bearing coumarin side chain.

A series of amino acid esters bearing coumarin (3-15) were synthesized and evaluated, in vitro, against HIV-1, and bovine viral diarrhea virus (BVDV). The in vitro cytotoxicity of 3-10 and 12 was assayed against a panel of tumor cell lines consisting of CD4 human T-cells. Compound 14 showed inhibition of HIV-1 with EC50 > 1.

Synthesis of N-substituted 1-amino-2,3-dihydro-1H-imidazole-2-thione-N-nucleosides and S-glycosylated derivatives.

Fusion of the N-substituted 1-amino-2,3-dihydro-1H-imidazole-2-thiones 1-4 with the peracylated ribose 5 in the presence of iodine afforded the N-nucleosides 6-9 in moderate yields. Deblocking with NaOMe/MeOH gave the free nucleosides 10-13. Alternatively, silylation of 4 followed by ribosylation with 5 in the presence of TMSOTf as catalyst afforded 9 in moderate yield.