Synthesis of 8-Trifluloromethyl-2-Thioquinazolin-( 3 H )-4-One Nucleosides

Synthesis of 8-trifluloromethyl-2-thioquinazolin-(1H,3H)-4-one 2. which have been ribosylated by coupling with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose 4 by using the silylation method, afforded β-anomeric of the benzoylated nucleoside derivatives 5. Debenzoylation of 5 by sodium metal in dry methanol to afford the corresponding free nucleosides 6. The structures of the newly synthesis compounds have been confirmed on the basis of elemental analyses, IR, HNMR, CNMR and Mass spectral data.

Thioquinazoline derivatives have interesting antimicrobial activity against different species of Gram positive bacteria, Gram negative bacteria and pathogenic Fungi, a possible pharmacophore for antitubercular activity and antiviral activity against TMV (Kottke, K., et al, 1997;Zhihua Wan, 2015).
Quinazolinone and thioquinazolinone nucleosides were first synthesized by Stout and Robins in 1968 as pyrimidine nucleoside analogs (Stout M. G and Robins R. K.,1968) and consequent synthetic studies were contributed by Dunkel and Pfleiderer in the 1990s (Hiroshi Takahashi, 1979;Dunkel M and Pfleiderer W, 1991, 1992and 1993).
In this review, 8-trifluloromethyl-2-thioquinazolin-(3H)-4-one nucleosides containing trifluloromethyl and thione groups were designed as part of our continuing interest in the synthesis of new nucleosides as expected their biological activity.

Material and Methods
Melting points were measured on Gallenkamp melting point apparatus (UK) and are uncorrected.The purity of the compounds was checked by thin layer chromatography (TLC).Thin layer chromatography (TLC) was performed on silica gel sheets F1550 LS 254 of Schleicher & Schull and column chromatography on Merck silica gel 60 (particle size 0.063-0.20.Elemental analyses were obtained on an Elementary Vario EL 1150C analyzer.IR spectra were recorded on KBr discs on Fourier Transform infrared and Pie Unicom SP 300 Infrared Spectrophotometers at Taif University. 1 H NMR and 13 C NMR spectra were obtained on a Varian (850 MHz) EM 390 USA instrument at King Abdel-Aziz University by using TMS as the internal reference.Mass spectra were recorded on a JEOL-JMS-AX500 at King Abdel-Aziz University, Saudi Arabia.

General Procedure
The pure anomer of each β 5 and (0.00151 mol, 1.45g), dry absolute methanol (20 ml) and sodium metal (0.055 g, 0.001mol) was stirred at room temperature for 48h.The solvent was evaporated under vacuum to give a colorless solid, which was dissolved in hot water and neutralized with few drops acetic acid.Purification of each compound by TLC chromatographic on silica gel with chloroform: ethyl acetate (9: 1) to afford colorless and white crystals of the following Zemplen et al.'s method (Zemplen et al, 1939) to afford the free nucleosides 6.

Results and Discussion
The structures of the products 2-6 were established and confirmed on the bases of their elemental analyses and spectral data (IR, 1 H and 13 C NMR) (see the Experimental section) (Scheme 1).Thus, their 1 H NMR spectra of compound 2 showed doublet signals at assigned to the aromatic protons of H-5 H-6 and H-7 and two a singlet signal of amide NH-3 and NH-1 at d 11.62, and 11.31, respectively.
The IR spectrum of compounds 5 and 6 showed the stretching vibration frequencies of the carbonyl C=O groups at 1725 cm −1 .IR spectra of compounds 6 showed absorptions around 3450 cm −1 for (OH) and 1715 cm −1 for (C=O).Debenzoylation of the latter affording the corresponding new free N-nucleosides 6. Compounds obtained have been identified by their spectral analysis.