5-Azido-3-cyclohexenecarboxylic acid was reduced to an aminocyclohexenylcarbinol which was coupled with either 5-amino-4,6-dichloropyrimidine or 2-amino-4,6-dichloropyrimidine, giving 5-pyrimidinyl-3-cyclohexencarbinols. Condensation with triethylorthoformate or nitrous acid formed the purine and 8-azapurine ring systems, respectively. Anti-HIV-1 and cytotoxicity testing results are also described.
Bibliographical noteFunding Information:
This work was supported by Public Health Service Grant CA23263 from the National Cancer Institute. We wish to thank Mr. Jay Brownell for conducting the P-388m ouse leukemia cytotoxicity studies. We also thank Dr. John P. Bader, Antiviral Evaluations Branch, National Cancer Institute, for the anti-HN screening results.
Elemental analyses were performed by M-H-W Laboratories, Phoenix, AZ. Melting points were determined on a Mel-Temp II apparatus and are corrected. The NMR spectra were obtained on a Bruker AC-200, Varian Unity 300 or Varian Unity 500 spectrometers and referenced to the solvent. Chemical shifts are expressed in ppm and coupling constants are in hertz. IR spectra were determined with KBr pellets (solids) or plates (oils) on a Nicolet 5DXC spectrometer and given in cm-1. Electron impact (EI) mass spectra (MS) were obtained with a Kratos/AEI MS-30 spectrometer, chemical impact (CI) MS were obtained with a Finnigan 4000 spectrometer, and fast-atom bombardment (FAB) MS were obtained with a VG 7070E-HF spectrometer. Thin-layer chromatography was performed on PolygramQ Sil G/UV254 (0.25 mm), column chromatography was performed on EM Science silica gel 60 (230 - 400 mesh), and preparative thin-layer chromatography was performed on EM Science silica gel 60 F254 (1.0 mm layer). DMF was dried over molecular sieves. All other solvents and chemicals are reagent grade unless specified otherwise. All stirring was done with magnetic stir bars. Cytotoxicities were determined using a previously reported protocol?5 and antiviral evaluation was carried out under the auspices of the National Institutes of Health.