Nucleosides 8 [ 18 ] : Ribosylation of Fused Quinazolines — Synthesis of New [ 1 , 2 , 4 ] Triazolo [ 5 , 1-b ]-and [ 1 , 2 , 4 ] Triazino [ 3 , 2-b ] quinazoline Nucleosides of Fluorescence Interest

[1,2,4]Triazolo[5,1-b]and [1,2,4]triazino[3,2-b] quinazolines have been ribosylated by coupling with 1-O-acetyl-2,3,5-tri-Obenzoyl-β-D-ribofuranose and by using the silylation method, followed by debenzoylation by methanolic sodium methoxide to afford the corresponding free N-nucleosides. Nucleosides obtained have been identified by their spectral analysis. From the UVvisible and fluorescence studies of some nucleosides synthesized, it is found that they have fluorescence properties.


Introduction
Most of the modified nucleosides prepared over the last years have been reported to be potential antiviral and chemotherapeutic agents.Quite a few are fluorescent, although most were not originally examined for their photophysical properties and were not employed as fluorescent probes [1][2][3][4].Other fluorescent nucleotide analogues have been developed but, when incorporated into DNA, they are quenched, destabilizing, or of limited sensitivity to environmental change.As a consequence, there is a strong demand for new fluorescent nucleoside analogues with improved spectroscopic properties and this is the purpose of intense research [5][6][7][8].In recent years there has been an increasing interest in the chemistry of 4(3H)-quinazolinones because of their biological importance.Many of them show antifungal, antibacterial, anticancer, anti-inflammatory, anticonvulsant, immunotropic, hypolipidemic, antitumor, antiulcer, analgesic, antiproliferative activities and inhibitory effects of thymidylate synthase and poly(ADP-ribose) polymerase (PARP) [9].
A variety of nucleoside derivatives have been prepared through the deletion or change in nature of the functional group present on the heterocyclic base or their sugar moieties.Such analogs permit the synthesis of oligonucleotides in which a single functional group at a preselected position has been deleted or otherwise altered.

Experimental
2.1.General.Melting points were determined on a Gallenkamp apparatus and are uncorrected.IR spectra were recorded in potassium bromide pellets using Perkin Elmer FTIR 1650 and Pye Unicam SP300 infrared spectrophotometers. 1 H-NMR and 13 C-NMR spectra were recorded in deuterated chloroform (CDCl 3 ) or deuterated dimethyl sulfoxide (DMSO- 6 ) using a Varian Gemini 300 NMR spectrometer.Thin layer chromatography was performed on silica gel sheets F 1550 LS 254 of Schleicher & Schuell and column chromatography on Merck silica gel 60 (particle size 0.063-0.20 mm).Mass spectra were recorded on a GCMS-QP 1000 EX Shimadzu and GCMS 5988-A HP spectrometers.UV-Vis spectra were measured by model 2450 a spectrophotometer (Shimadzu) and fluorescence spectra were measured by model RF-5301pc a spectrofluorometer (Shimadzu).Elemental analyses were carried out in the Microanalytical Laboratory of Cairo University, Giza, Egypt.The starting materials 2,3-diaminoquinazolin-4-one (1) [25] and ethyl benzoylpyruvate (18) [26] were prepared as in the literature reported methods.

Results and Discussion
Refluxing of the starting material 2,3-diaminoquinazolin-4-one (1), which is prepared according to the literature reported method [25], in triethyl orthoformate for 7 hours afforded one product, which is identified to be 3H [1,2,4] Although the products 2-5 are reported in the literature [25,27], no complete characterization data are found in the hand.
So, the structures of 2-5 were established and confirmed on the basis of their elemental analyses and spectral data (see Section 2).
With the aim of expanding the synthetic potential of the 2,3-diaminoquinazolin-4-one (1) formed, it is interesting to study the reaction of 1 with ethyl chloroacetate.When such reaction is carried out in relaxing pyridine/ethanol (v/v 1 : 1) yielded the new 4H [1,2,4]triazino [3,2-b]quinazolin-3,10-Dione (15) (Scheme 3).The structure of the product 15 was based on the assumption that the reaction in basic condition allowed it to proceed through elimination of sodium chloride from the basic 3-NH 2 , followed by cyclisation [28].
Also, the structure of the protected nucleosides 16 and 20 was confirmed by their IR, 1 H & 13 C NMR spectra, and microanalyses.Their IR spectra revealed three characteristic bands for (C=O)-stretching bands of product 16 and four bands for product 20 (see Section 2).The 1 H NMR spectra in CDCl 3 of 16 and 20 showed as in the case of that  However, debenzoylation of each of the blocked nucleosides, 7-10, 16, and 20 with methanolic sodium methoxide at room temperature for 48 h, yielded the corresponding free N-nucleosides, 11-14 (Scheme 1), 17 and 21 (Scheme 3), respectively.The 1 H NMR spectra of the free nucleosides 11-14, 17, and 21 showed the expected base moiety protons in addition to the sugar moiety protons (see Section 2).

Optical Properties
4.1.Introduction.Some quinazoline-based fluorescent nucleosides have been synthesized for photophysical studies and applications in probing nucleic acid structure, dynamics, and recognition [34].These size-expanded U analogues exhibit fluorescent emission wavelengths that span 155 nm, from 335 to 490 nm.Each nucleoside has unique characteristic response to changes in its microenvironment.These distinct features lead to a variety of applications in biological assays, many of which have been explored [34].
As part of our continuing interest are optical properties [35][36][37][38][39][40][41].We just perform the UV-visible and fluorescence     measurements of a series of fused quinazoline nucleosides prepared.Further studies of optical properties of such nucleosides are being under investigation and the results will be reported in due time.

UV-Visible Study.
Absorption spectra of all samples 2, 5, 7, 11, 15, 16, 17, 19, and 20 show an intense lowest energy charge-transfer absorption band in the UV-visible region.The position of this band is strongly influenced by the structure of the compounds, for example, by the type of  system (aryl or heteroaryl groups).The shifts of the absorption maxima are proportional to the intramolecular charge-transfer between the electron-releasing and withdrawing groups.In general, the stronger the donor and/or acceptor group, the smaller the energy difference between ground and excited states, and the longer the wavelength of absorption according to Chemla and Zyss [42].
As shown in Figure 1, the absorption spectra for all samples 2, 5, 7, 11, 15, 16, 17, 19 and 20 were measured as small volume samples in methanol in quartz cuvettes.The concentration of all samples are kept at 0.02 M in methanol.the effect of different solvents are simple, so we used one solvent for illustration the  max abs.and  max em.The absorption maximum and estimated optical band gaps ( op  ) are summarized in Table 1.It is well known that there are a lot of methods to determine band gap (  ) [43][44][45]; the optical band gap can be calculated also on the basis of the optical absorption spectrum [46,47].The low-wavelength absorption peak less than (349-405 nm) is attributed to the - * transition of donor units whereas the high-wavelength peak (483-575 nm) is believed to be related to the intramolecular - * transition between the ground and the excited states [48].

Fluorescence Study.
As shown in Figure 2, fluorescence spectra were carried out with all samples 2, 5, 7, 11, 15, 16, 17, 19, and 20 were kept at 0.02 M concentration in methanol.In order to relate the fluorescence properties to the nature of the nature of the donating and the acceptor groups attached to these moieties [49].
From the forgoing UV data ( max , in methanol, 286-368 nm) reported for some of our products, they are almost consistent with that of similar quinazolines derivatives which exhibit absorption wavelengths ( max , in methanol or acetone) from 280 to 399 nm [50,51].However, our products exhibit fluorescent emission wavelengths from 331 to 390, while some quinazoline-based fluorescent nucleosides have been synthesized for photophysical studies that exhibit fluorescent emission wavelengths from 335 to 490 nm [34], depending upon their chromophores.

Conclusion
Silylation method was found to be a convenient method for the ribosylation of [1,2,4] 16 and 20, respectively.Deprotection of the latter by using methanolic sodium methoxide gave new free N-nucleosides 11-14, 17, and 21, respectively, in moderate yields.Nucleosides obtained have been identified by their spectral analysis.In agreement with the results obtained from the UV-visible, fluorescence studies, the samples 2, 5, 7, 11, 15, 16, 17, 19, and 20 synthesized can be applied for the manufacture of new materials with nonlinear optical (NLO) properties [52], as fluorescent markers, due to their strong fluorescence, or as light emitters in organic light emitting devices (OLEDs) [53].

Table 1 :
Optical properties of the products 2