http://www.revistadechimie.ro REV.CHIM.(Bucharest)♦68♦No. 10 ♦2017 2228 Preparation of New Oxadiazole Acyclic Nucleoside and Thioglycoside Analogs Containing Chromene Moiety with Antimicrobial Evaluation MSHARI A. ALOTAIBI 1 , FARAG A. EL ESSAWY 2,3 , NADER M. BOSHTA 3 * 1 Department of Chemistry, Collage of Science and Humanities, Prince Sattam Bin Abdulaziz University, 83Alkharj 11942, KSA 2 Preparatory Year Deanship, Basic Science Department, Prince Sattam Bin Abdulaziz University, 151 Alkharj 11942, KSA 3 Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koam, Egypt New sugar hydrazones linked to chroman ring system and their derived oxadiazole acyclic nucleoside analogs were synthesized from the substituted ethyl ester oxime derivative. The 2-sustituted 1,3,4-oxadiazole- 5-thione prepared from acid hydrazide was glycosylated to afford the corresponding thioglycosides, not the N-linked glycosides. The novel compounds were evaluated for their antimicrobial activity and showed different degrees of activities. Keywords. Chromene; Oxadiazole; Acyclic Nucleoside; Antimicrobial * email: nboshta@uni-bonn.de; Phone: +4917695525230 Chromenes and fused chromenes are biologically interesting compounds with antimicrobial activities [1–3], inhibitors of influenza virus sialidases [4,5], DNA stand breaking activity, and mutagenicity [6]. It is also known that many chromene containing compounds exhibit a wide spectrum of pharmacological activities [7,8], anti-HIV agents [9,10], antibacterials [11,12], and antifungals [13]. In general, a number of biologically active chromenes and chromanes have been isolated from several natural sources. These substances have identified as apoptosis- inducing [14]. Among the ûve-membered nitrogen heterocycles, the 1,3,4-oxadiazoles are known to be associated with a broad spectrum of biological activities [15–17]. Their derivatives have been known to possess antibacterial [18], herbicidal, fungicidal [19], anti- inûammatory [20], hypoglycaemic [21], and hypotension characteristics [22], as well as antiviral [23] and anti- tumour activities [24]. Otherwise, the glycosylthio heterocycles [25-27] and the acyclic nucleoside (analogs with modification of both the glycon part and the heterocyclic base) have encouraged comprehensive research as biological inhibitors [28-30]. Several reports have documented the biological activity of Nucleosides and their analogs including antibiotic, antiviral, and antitumor activity [31–35]. Cyclization of diacylhydrazines is one of the preparation procedures of 1,3,4-Oxadiazole ring system [3]. In this context and also our interest in the synthesis of heterocyclic compounds holding the chromene system [38-40] and attachment of carbohydrate moieties to newly synthesized heterocycles, our aim is to synthesize a new oxadiazole acyclic nucleosides linked to chroman ring and their thioglycoside derivatives in an ongoing search for new biologically active derivatives with antimicrobial activity . Experimental part General methods All reagents were used in analytical grades. Solvents were desiccated if necessary by standard methods. Reactions were monitored by TLC (silica gel 60F254, Merck, Darmstadt, Germany). Melting points were determined on a melting point apparatus (Stuart Scientific, Stone, Staffordshire, UK) and were uncorrected. The IR spectra were recorded on a perkin-Elmer 1720 FTIR spectrometer (cm -1 ), using KBr disks. NMR spectra were carried out with a 300 MHz at Cairo University. Chemical shifts ( δ) are reported in parts per million (ppm) relative to the respective solvent or tetramethylsilane (TMS) as internal standard and standard abbreviations were used (a = apparent; b = broad; s = singlet; d = doublet; t = triplet; q = quartet; m = multiplet). Elemental analyses were performed at the Micro analytical data centre at Faculty of science, Cairo University, Egypt. Antimicrobial screening was conducted at the botany department, faculty of science, Menoufia University. Ethyl 2-(2,2-dimethylchroman-4-ylideneamino- oxy)acetate (3) To a solution of compound 2 (1.91 g, 10 mmol) and dry potassium carbonate (1.40 g, 10 mmol) in 15 mL acetone, ethyl chloroacetate (1.20 g, 10 mmol) was added. The reaction mixture was allowed to stir at room temperature for 6 h and then poured onto ice water. The solid separated out was filtered off, washed with water and recrystallized from ethanol to give compound 3 as white crystals, Yield 2.22 g (83%), mp 129-130 °C; IR (KBr) ν: 1740 (C= O), 1600 (C= N), 1181 (C-O) cm -1 ; 1 H NMR (CDCl 3 , 300 MHz) δ: 1.03 (t, 3H, J = 3.5 Hz CH 2 CH 3 ), 1.27 (s, 6H, 2CH 3 ), 2.90 (s, 2H, CH 2 ) 4.89 (q, 2H, J = 5.2 Hz, CH 2 CH 3 ), 503 (s, 2H, CH 2 ), 7.29-7.33 (m , 4H, ArH); 13 C NMR (CDCl 3 , 75 MHz) δ: 15.20, 20.35 (3 CH 3 ), 33.39,(CH 2 ), 61.07 (CH 2 ), 72.15 (CH2), 81.15 ( C(CH3) 2 ), 112.56, 117.66, 118.22, 121.77, 127.32, 151.33, 166.11 (C= N), 169.18 (C= O). An a l. Calcd for C 15 H 19 NO 4 (277.13): C, 64.97; H, 6.91; N, 5.05. Found: C, 64.02; H, 6.53; N, 5.27. 2-(2,2-Dimethylchroman-4-ylideneaminooxy) acetohydrazide (4) In a (25 mL) one-necked flask, 3 (2.77 g, 10 mmol) and hydrazine hydrate (0.5 g, 10 mmol) were dissolved in (20 mL) absolute ethanol. The mixture was heated to reflux for 3 h and after that, the solvent was concentrated under reduced pressure and the resulting precipitate was filtered off, washed with ethanol and recrystallized from ethanol to afford compound 4 as white crystals, Yield 1.98 g (72%), mp 197-198 °C; IR (KBr) ν: 3431-3375 (NH 2 and NH), 1690 (C= O), 1604 (C= N) cm -1 ; 1 H NMR (CDCl 3 , 300 MHz) δ: 1.32 (s, 6H, 2CH 3 ), 2.95 (s, 2H, CH 2 ), 4.75 (s, 2H, CH 2 ), 5.03