Synthesis and Antibacterial activities of some Arabinofuranose-Schiff bases Derivatives

As a continuous research for the discovery of new antibacterial agents due to the developing resistance toward conventional antibiotics, we reported a convenient synthetic approach for the preparation of methyl-α-D-arabinofuranoside shiff-bases. A series of arabinose-Shiff bases were prepared through the trityl protection of the primary hydroxyl group of methyl-α-D-arabinofuranoside, benzoylation, the removal of the trityl protective group, tosylation, azidation, conversion to the amine in the presence of triphenylphosphine, condensing reaction with a variety of aromatic aldehydes, and subsequent debenzoylation. New compounds were characterized by 1 H NMR and FTIR spectroscopy. Synthesised compounds were screened for antibacterial activity against several bacterial strains namely, Escherichia coli; Staphylococcus aureus; Bacillus subtilis; Candida albicans; Aspergillus niger, and they showed enhanced antibacterial activity.


INTRODUCTION
Schiff bases are known as imine or azomethine. Structurally these are nitrogen analogue of an aldehyde or ketone [1], [2]. Schiff bases are formed by the condensation of aldehydes and the amine group. Compound containing imines bases have been found to stand extensive application in organic synthesis, in addition, several of these molecules display significant pharmacological activities such as antimicrobial, antimalarial, antitubercular, anticancer, antihelmintic, antioxidant, analgesic and antiinflammatory [3], [4], [5]. Many studies have illustrated that aromatic nucleus Schiff bases had significant bioactivities [6]. Carbohydrates are biologically important substrate. Their chemical modification can provide new compounds and materials with interesting physicochemical and biological properties [7]. Inulin consists primarily of β-fructosylfructose units, always presented in furanose form [8]. Study showed that inulin Schiff bases derivatives containing benzene, have antifungal activity against different kinds of phytopathogens and exhibit higher inhibition indices than inulin. These data established that the chemical modification of inulin would lead to an enhancement of the biological activity against some plant pathogenic fungi [9]. Arabinofuranose (Araf) is a very common structural constituents of polysaccharide present in many lower organisms including bacteria [10], [11], parasites [12], and fungi [13]. Polysaccharide of Araf are major components of the cell wall of mycobacterial, including the human pathogens Mycobacterium tuberculosis and Mycobacterium leprae [14]. The ability of the organism to make these polysaccharides is crucial to its survival and pathogenicity [15]. Chemical synthesis of the structural fragments of these polysaccharide is holding current appeal, as the synthetic fragments play significant roles not only in probing the biosynthetic pathway by which these glycans are assembled [16], but also in exploring new oligosaccharide-based inhibitors that target the enzymes [17].
Looking at the role of Araf, Schiff base and carbohydrate in medicinal chemistry, it was planned to synthesis some diverse shiff bases of Araf using different aromatic aldehydes in alkaline medium and evaluation their antibacterial activities.

MATERIAL AND METHODS
Melting points were measured using a Gallenkamp melting point apparatus. Infra-red spectra were recorded as KBr discs (solids) or thin films on NaCl windows using a Perkin Elmer 1600 series FTIR spectrometer. NMR spectra were recorded on Bruker Avance 400

Methyl 2,3-di-O-benzyl-α-D-Araf (5)
Benzoyl chloride (168.6 mL, 1.18 mmol) in anhydrous pyridine (150 mL) was added to a stirred solution of (3) (9.9 g, 23.6 mmol) at 0 ºC. The reaction mixture was allowed to reach room temperature and stirred at 40 ºC for 1.5 h then TLC showed no starting material was left, the mixture was cooled to 0 ºC and ice chips (150 g) was added.

Methyl 2,3-di-O-benzoyl-5-amino-5-deoxy-α-D-Araf (8)
To a stirred solution of compound (7) (10 g, 25 mmol) in (200) mL of anhydrous DMSO, Ph 3 P (7 g, 26 mmol) was added and the reaction mixture was stirred for 24 h at room temperature. Water (10 mL) was added to the mixture and the solution was stirred for a further 24 h. The reaction mixture was poured into 500 mL acetone and the product was collected, washed 3 times by ethanol and acetone, and dried in vacuum to give the azide (8)

General procedure for the synthesis of Schiff bases of Araf (10a-g).
To a solution of compound (8) (0.005 mol) in methanol (20 mL), the corresponding aldehyde (0.02 mol) was added. To this mixture, KOH (0.1 % in methanol) was added to adjust the pH of the solution between 7-8 and then the mixture respectively was refluxed for 4 h. After completion reflux, Schiff base (9a-g) was separated out on removal of the solvent at room temp. The final compound was subjected to a hydrolysis by adding sodium methoxide (0.1 M, in methanol, 6.0 mL) to a stirred solution of compounds of (9a-g) (0.01 g) in dry MeOH : CH 2 Cl 2 (1:1, 8 mL) at room temperature and the reaction mixture was stirred for 5 h then TLC showed no starting material was left. The reaction mixture was neutralized with Amberlite IR-120 (H + ), the resin was filtered off and the solvent was removed under reduced pressure to give a residue which was purified by column chromatography on silica eluting with dichloromethane/methanol (5:1) to afford the desired compound (10a-g). Synthesised compounds were proved by 1 HNMR and IR spectroscopy.

CONCLUSION
In conclusion, we have achieved the synthesis of novel Shiff bases of Araf (10a-g) derived from methyl 2,3-di-O-benzoyl-5-amino-5-deoxy-α-D-Araf and different aromatic aldehydes in good yields. Their antimicrobial activities were studied against various microorganisms, and the results showed that the synthesized derivatives had antibacterial activities. More tests and assays on these compounds are in progress.