DOI: 10.17344/acsi.2016.2727
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Scientific paper
Synthesis and Biological Evaluation of Triazole linked Thiazolidenone Glycosides
Avula Srinivas,1'* Madavarapu Santhosh,1 Malladi Sunitha,1 Pulluri Karthik,1 Kontham Srinivas and K.Vasumathi Reddy2
1 Department of Chemistry, Vaagdevi Degree & PG College
2 Department of Zoology, Vaagdevi Degree & PG College Kishanpura, Warangal, Telangana, India 506001
* Corresponding author: E-mail: avula.sathwikreddy@gmail.com
Received: 10-07-2016
Abstract
In a one pot procedure a series of novel triazole linked thiazolidinone derivatives 8a-g and 9a-g was prepared by condensation of (3aR,5S,6R,6aR)-6-((1-(4-chlorophenyl)-1^-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydro[2,3-d] [1,3]dioxole-5-carbaldehyde 7 with mercapto acids and primary amines in the presence of ZnCl2 under both microwave irradiation and conventional heating conditions. Compound 7 was prepared from diacetone D-glucose with oxidation followed by reduction, click reaction, primary acetonide deprotection and with oxidative cleavage. Characterization of new compounds has been done by means of IR, NMR, MS and elemental analysis. The nematicidal and antibacterial activity of the compounds has also been evaluated.
Keywords: Swern oxidation, click reaction, cyclisation, antibacterial and nematicidal activity.
1. Introduction
1,2,3-Triazoles are one of the most important classes of heterocyclic organic compounds, which are reported to be involved in a plethora of biological activities and important for diverse therapeutic areas.1 The 1,2,3-triazole motif is associated with diverse pharmacological activities such as antibacterial, antifungal, hypoglycemic, antihypertensive and analgesic properties. Polysubstituted five-membered aza heterocyclices rank as the most potent glycosidase inhibitors.2 Further, this nucleus in combination with or in linking with various other classes of compounds, such as ami-no acids, steroids, aromatic compounds, carbohydrates etc., becames prominent in having various pharmacological pro-perties.3 1,2,3-Triazole modified carbohydrates have became easily available after the discovery of the Cu(I) catalyzed azide-alkynes 1,3-dipolar cycloaddition reaction4 and quickly became a prominent class of non-natural sugars. The chemistry and biology of triazole modified sugars is dominated by triazole glycosides.5 Therefore, the synthesis and investigation of biological activity of 1,2,3-triazole glycosides is an important objective, which also received the considerable attention by the medicinal chemists.
Thiazolidenone and its derivatives are known to possess significant pharmacological6 and biological activities,7 like sedative,8 anti inflammatory,9 anti tubercular,10 anticancer,11 antitumor,12 anti-HIV,13 antibacterial,14 antifungal,15 analgesic, hypothermic,16 anesthetic,17 nematicidal18 and CNS stimulant.19 Furthermore, thiazolidenones have been used for the treatment of cardiac diseases,20 diabetic complications, like cataract nephropathy, neuro-pathy,21 and as selective anti platelet activating factor.22
Nematodes are tiny worms, some of them are plant parasites, and can play an important role in the predisposition of the host plant to the invansion by secondary patho-gens.23 Plants attacked by nematodes show retarded growth and development, as well as loss in the quality and quantity of the harvest. The use of nematicides is slated for reduction due to environmental problems, and human and animals health concerns. For example, effective na-maticides such as dibromochloropropane (DBCD) and ethylene dibromide (EDB) have been withdrawn from the market due to their deleterious effects on humans and the environment. Methyl bromide, the most effective and widely used fumigant for soil borne pests including nemato-des, has already been banned.
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The use of nonfumigant nematicides, based on or-ganophosphates and carbamates, is expected to increase after the withdrawal of methyl bromide, which will bring about new environmental concerns. In fact, the highly toxic Aldicarb used to control insects and nematodes has been already detected in ground water.24 Therefore alternative nematode control methods or less toxic nematici-des need to be developed. One way of searching for such nematicidal compounds is to screen naturally occurring compounds in plants. Several such compounds, e.g. alkaloids, phenols, sesquiterpenes, diterpenes, polyacetyle-nes, and thienyl derivatives have nematicidal activity.25 For example, -terthienyl is a highly effective nematicidal compound.26 Other compounds with nematicidal activity have been isolated from plants, mainly from the family Asteraceae.25 However, compounds of plant origin and their analogs have not been developed into commercial nematicides; hence there is a need to develop commercial synthesis.
Following the successful introduction of antimicrobial and nematicidal agents, inspired by the biological profile of triazoles, thiazolidenones, and in the continuation of our work on biologically active heterocycles,27-39 we have developed a series of novel triazole linked thiazo-lidenone derivatives, and evaluated their nematicidal activity along with antibacterial activity.
2. Result and Discussion
Diacetone D-glucose (1), prepared from D-(+)-glu-cose by treating with acetone in the presence of catalytic amount of sulphuric acid according to the literature proce-dure,40 reduction of 2 (prepared by Swern oxidation of 1) with NaBH4 in aq. ethanol at 0 °C for 1 h gave 3 (77%), which on subsequent propargylation in DMF in the presence of NaH for 1 h afforded propargyl ether 4 (80%). Next, the propargyl ether 4 was converted into triazole 5 (82%) by using 1,3-dipolar cycloaddition with p-chlorop-henyl azide carried out at ambient temperature in the presence of CuSO4 and sodium ascorbate in a mixture of 1:1 t-BuOH-H2O, as reported by Sharpless. Acid hydrolysis of 5,6-acetonide 5 in 60% AcOH furnished the diol 6 (85%), which on oxidative cleavage with NaIO4 gave the aldehyde 7. Subsequently, one pot synthesis of triazole linked thiazolidenone glycosides was carried out by the condensation reaction between 7, primary aromatic amine and a thioglycolic acid in the presence of ZnCl2 under microwave irradiation or conventional heating (Scheme 2). In classical method the reactions were performed in dry toluene at reflux for a long time (2-4 h), often leading to degradation processes and consequent low yields of isolated products, whereas with the application of microwave assisted technology, the reaction was completed in only 5-10 min and the compounds, isolated by conventional work-up, were obtained in satisfactory yields, often hig-
her than those achieved by traditional methods (Table 1). The structures of synthesized compounds were confirmed by IR, NMR, MS and elemental analysis. Further the compounds were subject to nematicidal and antibacterial testing.
3.	Antibacterial Activity
Compounds 8a-g and 9a-g were screened for their antibacterial activity using the tube dilution method41 by measuring the minimum inhibitory concentration (MIC) in |ag/mL against four representative organisms, viz. Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Staphylococcus pyogenus. Standard antibacterial agents, such as streptomycin and Neomycin, were also screened under identical conditions for comparison. The minimum inhibitory concentrations are given in Table 2. However, it has been observed that the test compounds exhibited an interesting biological activity, with degree of variation.
Compounds in series 8 and 9, which contain 4-Cl or 3-OH groups, displayed good antibacterial activity against all the organisms. Compounds 8b and 9f were highly active against all the organisms. Compounds 8b and 9f were highly active against B. subtilis, S. aureus and S. pyogenus, compound 9f was highly active against B. subtilis, S. aureus, E. coli, compound 9b was highly active against B. subtilis, E. coli and S. pyogenus and the compound 8c was highly active against E. coli and S. pyogenus. Compounds 9a and 9d did not exhibit any activity against E. coli, even at 100 ^g/mL concentration. The alkyl substituted derivatives displayed moderate levels of antibacterial activity (Table 2).
4.	Nematicidal Activity
Compounds 8a-g and 9a-g were also screened for their nematicidal activity against Ditylenchus mycliopha-gus and Caenorhabditis elegans by aqueous in vitro screening technique42 at various concentrations. The results have been expressed in terms of LD50, i.e. median lethal dose at which 50% of nematodes became immobile. The screened data reveal that compound 8f and 9f are the most effective against D. myceliophagus and C. elegans with LD50 values of 210 and 240 ppm, respectively.
5. Experimental
Commercial grade reagents were used as supplied. Solvents except analytical reagent grade were dried and purified according to literature, when necessary. Reaction progress and purity of the compounds were checked by thin-layer chromatography (TLC) on pre-coated
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Sheme 1
o^O a V\
+ 2R NH2
Cl
N-N
A
V
o
Cl
Sheme 2
Reagents and conditions: (a) COCl2, CH2Cl2, Et3N, -78 oC > rt, 1.5 h; (b) NaBH4, EtOH, H2O (19:1), 0 oC > rt; (c) propargyl bromide, NaH, DMF, 0 oC > rt; (d)p-chlorophenyl azide, sodium2 ascorbate, CuSO4-5H2O, i-BuOH/H2O; (e) 60%, AcOH; (f) NaIO4, CH2Cl2; (g) Ar-NH2, SHCH2COOH, ZnCl2 toluene , 80 oC; (h) Ar-NH2, thiomalic acid, ZnCl2 toluene, 80 oC.
silica gel F254 plates from Merck and compounds were visualized either by exposure to UV light or dipping in 1% aqueous potassium permanganate solution. Silica
gel chromatographic columns (60-120 mesh) were used for separations. Optical rotations were measured on an Perkin-Elmer 141 polarimeter by using a 2 mL cell with
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Table 1: Synthesis of Compounds 8a-g and 9a-g
Compound	R	Mol. Formula	Reaction time A (h) B (min)		Yield A	B
8a	C6H5	C25H25CIN4O5S	3.5	5	62	80
8b	4-CI-C6H4	C25H24Cl2N4O5S	2.5	6	71	89
8c	4-NOrC6H4	C25H24CIN5O7S	3.0	6	69	82
8d	2-CH3-C6H4	C26H27CIN4O5S	2.0	5	63	86
8e	4-CH3-C6H4	C26H27CIN4O5S	2.5	5	68	88
8f	3-OH-C6H4	C25H25CIN4O6S	3.0	5	79	86
8g	4-OH-C^4	C25H25CIN4O6S	2.0	3	80	91
9a	C6H5	C27H27ClN4O7S	3.5	5	63	79
9b	4-CI-C6H4	C27H26Cl2N4O7S	2.5	6	65	82
9c	4-NO2-C6H4	C27H26Cl2N5O9S	3.0	7	61	79
9d	2-CH3-C6H4	C28H29CIN4O7S	2.5	5	70	81
9e	4-CH3-C6H4	C28H29CIN4O7S	2.0	5	67	82
9f	3-OH-C6H4	C27H27CIN4O8S	3.0	5	77	87
9g	4-OH-C66H44	C27H27CIN4O8S	2.5	4	79	90
A: conventional heating, B: microwave irradiation
Table 2. Antibacterial and nematicidal activity of 8a-g and 9a-g
Compound	Anti bacterial activity Minimum inihibitory concentration (MIC, ^g/mL) B. subtilis S. aureus E. coli S. pyogenes				Nematicidal activity D. myceliophagus C. elegans	
8a	50	25	50	50	940	960
8b	12.5	12.5	25	12.5	360	400
8c	25	25	12.5	12.5	440	390
8d	25	50	25	25	610	650
8e	100	50	50	50	1070	1010
8f	12.5	12.5	12.5	50	210	320
8g	50	50	100	25	420	670
9a	50	50	-	25	710	650
9b	12.5	25	12.5	12.5	400	350
9c	25	25	25	12.5	490	510
9d	50	100	-	50	1030	1050
9e	50	50	50	50	910	970
9f	12.5	12.5	25	12.5	360	240
9g	50	25	50	50	660	540
Streptomycin 10	10	10	10	-	-	
Neomycin 30	30	30	30	-	-	
a path length of 1 dm with CHCl3 or CDCl3 as solvent. Microwave reactions are carried out in a mini lab microwave catalytic reactor (ZZKD, WBFY-201). All melting points are uncorrected and measured using Fisher-Johns apparatus. IR spectra were recorded as KBr disks on a Perkin-Elmer FT IR spectrometer. The 1H NMR and 13C NMR spectra were recorded on a Varian Gemini spectrometer (300 MHz for 1H and 75 MHz for 13C). Chemical shifts are reported as 5 in ppm against TMS as internal reference and coupling constants J are reported in Hz units. Mass spectra were recorded on a VG micro mass 7070H spectrometer. Elemental analyses (C, H, N) were determined by a Perkin-Elmer 240
CHN elemental analyzer and were within ±0.4% of theoretical values.
(3afl,5fl,6aS)-5-((fl)-2,2-Dimethyl-1,3-dioxolan-4-yl) -2,2-dimethyldihydrofuro[3,2-d][1,3]dioxol-6(3a_ff)-one (2). Dissolved 8.5 mL of oxalylchloride in 20 mL of dry CH2Cl2. Stirred, cooled to -78 °C. Added 14 mL of DMSO. Added a solution of 5 g of alcohol in 30 mL of CH2Cl2. Stirred for 45 min. Added 40 mL Et3N. After 15 min, warmed to 0 °C. After 10 min TLC showed complet reaction. The reaction mixture was placed on silica gel column and the product was purified column chromatography (Silica gel 60-120 mesh, 10% ethyl
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acetate in hexane) gave 3 quantitative yield (4.5 g) as a yellow syrup, which was used as such for the next reaction.
(3aR,5S,6R,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[3,2-d][1,3]dioxol-6-ol (3). To a stirred solution of 2 (4.5 g, 19 mmol) in aq. etha-nol (EtOH-H2O 19 : 1; 100 mL), NaBH4 (0.37 g, 9.7 mmol) was added at 0 °C and then reaction mixture was stirred for 1 h. Solvent was evaporated in vaccuo, residue treated with saturated NH4Cl solution (10 mL) and stirred at room temperature for additional 10 min. The reaction mixture was extracted with EtOAc (2 x 50 mL) and organic layer separated was washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated. Residue obtained was purified by column chromatography (60-120 mesh silica gel , 60% ethyl acetate in pethrol ether) to afford 3 (3.8g , 80%) as a white solid; mp 82 oC; [a]20D = +82.49 (c 1.62, CHCl3); IR (KBr): v 3413, 2994, 2927, 1632, 1375, 1220, 1162, 1072, 1010 cm-1; 1H NMR (300 MHz, CDCl3, 298 K): 5 5.75 (d, 1H, J = 3.7 Hz, C1H), 4.56 (d, 1H, J = 4.2 Hz, C2H), 4.23 (m, 1H, C5H), 4.07-3.91 (m, 3H, C4H, 2 x C6H), 3.74 (dd, 1H, J = 8.0, 4.3 Hz, C3H), 2.44 (d, 1H, J = 8.4 Hz, OH), 1.56 (s, 3H, CH3), 1.4^1 (s, 3H, CH3), 1.36 (s, 6H, 2 x CH3); 13C NMR (75 MHz, CDCl3): 5 112.8, 109.8, 103.9, 79.7, 79.0, 75.5, 72.5, 65.8, 26.6, 26.5, 26.3, 25.3; MS: m/z (M++Na) 283.1171.
(3aR,5R,6R,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-6-(prop-2-ynyloxy)tetrahydrofu-ro[3,2-d][1,3]dioxole (4). Sodium hydride (60% in mineral oil, 0.64 g) was added to a stirred solution of 3 (3.6 g, 13.84 mmol) in DMF (80 mL) at 0 °C and allowed to stir for 30 min. This yellow mixture was cooled to 0 °C and treated with propargyl bromide (4.2 g) in DMF (20 mL). The dark brown reaction mixture was allowed to stir for an hour at room temperature and quenched (at 5-10 °C) with saturated aqueous ammonium chloride (20 mL). The crude product was extracted with methylene chloride (3 x 30 mL), dried (Na2SO4) and concentrated. The residue was purified by column chromatography on silica gel (5% ethyl acetate-hexane) to afford 4 (3.1 g, 75%) as viscous oil. [a]20D = -6.3 (c 1.7, CHCl3). IR (KBr): v 3310, 2995, 2928, 2268, 1634, 1379, 1224, 1164, 1075, 1018 cm-1; 1H NMR (300 MHz, CDCl3): 5 5.62 (d, J = 3.7 Hz, 1H, C1H), 4.69 (t, J = 3.9 Hz, 1H, C2H), 4.36 (dt, J = 3.1, 7.3 Hz, 1H, C5H), 4.21 (s, 2H, CH2), 4.09-3.96 (m, 3H, C4H, 2 x QH), 3.68 (dd, J = 8.9, 4.1 Hz, 1H, C3H), 3.19 (s, 1H, CH), 1.56 (s, 3H, CH3), 1.42 (s, 3H, CH3), 1.36 (s, 6H, 2 x CH3); 13C NMR (751MHz, CDCl3): 5 112.7, 109.5, 103.8, 80.2, 77.6, 77.2, 74.6, 66.2, 57.2, 26.6, 26.2. MS: m/z (M++Na) 321.10.
1-(4-Chlorophenyl)-4-(((3aR,5R,6R,6aR)-5-((R)-2,2-di-methyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofu-
ro[3,2-d][1,3]dioxol-6-yloxy)methyl)-1H-1,2,3-triazole (5). To a solution containing alkyne 4 (3 g, 10.06 mmol), p-chlorophenyl azide (1.8 g, 11.76 mmol) in dichloro methane (30 mL) and water (30 mL) were added CuSO4 ■ 5H2O (1.8 g, 8.15 mmol) and sodium ascorbate (1.2 g). The resulting suspension was stirred at room temperature for 4-6 h. After this time, the mixture was diluted with 20 mL dichloromethane and 20 mL water. The organic phase was separated, dried with sodium sulfate and concentrated at reduced pressure, the crude residue was purified by column chromatography on silica gel (60-120 mesh, 35% EtOAc-hexane) to afford 5 (3.2 g, 75%) as a white powder. mp 159-161°C. [a]20D = -91.3 (c 1.7, CHCl3). IR (KBr): v 3250, 2975, 2928, 1634, 1554, 1512, 1376, 1220, 1168, 1072, 1020, 736 cm-1; 1H NMR (300 MHz, CDCl3): 5 8.05 (s, 1H, Ar-H), 7.56 (d, J = 9.2 Hz, 2H, ArH), 7.45 (d, J = 8.9 Hz, 2H, Ar-H), 5.59 (d, J = 3.7 Hz, 1H, C1H), 4.65 (t, J = 3.9 Hz, 1H, C2H), 4.59 (s, 2H, CH2), 4.39 (dt, J = 3.1, 7.3 Hz, 1H, C5H), 4.09-3.96 (m, 3H, C4H, 2 x C6H), 3.71 (dd, J = 8.9, 4.1 Hz, 1H, C3H), 1.54 (s, 3H, CH3), 1.40 (s, 3H, CH3), 1.34 (s, 6H, 2 x CH3); 13C NMR (75 MHz, CDCl3): 5 144.1, 134.5, 122.4, 119.5, 112.5, 109.6, 103.6, 80.0, 77.4, 74.2, 67.5, 66.2, 26.6, 26.2, 24.9. MS: m/z (M++H) 452.10. Anal. Calcd for C21H26ClN3O6: C, 55.81; H, 5.80; N, 9.30. Found: C, 55.75; H, 5.75; N, 9.21.
(R)-1-((3aR,5R,6R,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofu-ro[3,2-d][1,3]dioxol-5-yl)ethane-1,2-diol (6). A mixture of 5 (3 g, 6.65 mmol) in 60% aq. AcOH (25 mL) was stirred at room temperature for 12 h. Reaction mixture was neutralized with anhy. NaHCO3 (15 g) and extracted with EtOAc (3 x 41 mL). The combined organic layers were dried (Na2SO4), evaporated and residue purified by column chromatography (60-120 mesh silica gel, 41% EtOAc-pethroleum ether) to afford 6 (2.6 g, 82%) as a pale yellow solid. mp 168-171°C IR. (KBr): v 3228, 3486, 3372, 2994, 2975, 2946, 2928, 1634, 1554, 1512, 1217, 1164, 1020, 736 cm-1. 1H NMR (300 MHz, CDCl3): 5 8.03 (s, 1H, Ar-H), 7.54 (d, J = 9.2 Hz, 2H, ArH), 7.43 (d, J = 8.9 Hz, 2H, Ar-H), 5.51 (d, J = 3.7 Hz, 1H, C1H), 4.56 (t, J = 3.9 Hz, 1H, C2H), 4.59 (s, 2H, OCH2), 3.98-3.93 (m, 2H, C4H, C5H), 4.01-3.92 (m, 3H, C3H, 2 x C6H), 2.44 (bs, 1H, OH), 1.54 (s, 3H, CH3), 1.50 (bs, 1H, OH), 1.34 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 144.2, 134.2, 122.1, 119.2, 112.2, 109.2, 103.1, 79.8, 77.1, 74.1, 67.2, 66.2, 64.2, 70.6, 26.6, 26.2, 24.9. MS: m/z (M++H) 412.10. Anal. Calcd for C18H22ClN3O6: C, 52.49; H, 5.38; N, 10.21. Found: C, 52.35; H, 5.25; N, 10.211.
2-((3aR,5S,6S,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-phenylthiazolidin-4-one (8a-g).
To a solution of diol 6 (0.200 g, 0.48 mmol) in CH2Cl2 (5 mL), NaIO4 (0.130 g, 0.61 mmol) was added at 0 °C and
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stirred at room temperature for 6 h. The reaction mixture was filtered and washed with CH2Cl2 (2 x 10 mL). It was dried (Na2SO4) and evaporated to give aldehyde 7 (0.150 g) in quantitative yield as a yellow liquid, which was used as such for the next reaction.
To a stirred mixture of 7 (0.150 g, 0.395 mmol), aromatic amine (0.395 mmol) and anhydrous thioglycolic acid (0.160 g, 0.211 mmol) in dry toluene (5 mL), ZnCl2 (0.100 g, 0.751 mmol) was added after 2 min and irradiated in microwave bath reactor at 280 W for 4-7 minutes at 110°C. After cooling, the filtrate was concentrated to dryness under reduced pressure and the residue was taken up in ethyl acetate. The ethyl acetate layer was washed with 5% sodium bicarbonate solution and finally with brine. The organic layer was dried over Na2SO4 and evaporated to dryness at reduced pressure. The crude product thus obtained was purified by column chromatography on silica gel (60-120 mesh) with hexane-ethyl acetate as eluent. Under conventional method the reaction mixture in toluene (10 mL) was refluxed at 110 °C for the appropriate time (Table 1).
2-((3afl,5S,6S,6afl)-6-((H4-ChlorophenylM#-1,2,3-
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-rf][1,3]dioxol-5-yl)-3-phenylthiazolidin-4-one (8a). mp
147-149°C; IR (KBr) v 3432, 3230, 2986, 2975, 2944, 2836, 1716, 1612, 1551, 1512, 1416, 1221, 687 cm-1. 1H NMR (300 MHz, CDCl3): 5 8.06 (s, 1H, Ar-H), 7.52 (d, J = 9.2 Hz, 2H, Ar-H), 7.42 (d, J = 8.9 Hz, 2H, Ar-H), 7.52-6.90 (5H, m, Ar-H), 5.75 (d, J = 3.6 Hz, 1H, C1H), 4.93 (d, J = 5.2 Hz, CH-S), 4.62 (t, J = 3.9 Hz, 1H, C2H), 4.52 (s, 2H, OCH2), 3.98-3.95 (m, 1H, C4H), 3.75 (s, 2H, CH2), 3.31 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 1.55 (s, 3H, CH3), 1.32 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 171.6, 144.2, 141.2, 134.8, 134.2, 128.9, 128.2, 127.4, 122.2, 119.6, 119.2, 104.8, 81.2, 78.5, 74.4, 66.9, 52.0, 34.6, 26.5; MS: m/z (M++Na) 552.10. Anal. Calcd for C^H^ClN^S: C, 56.76; H, 4.76; N, 10.59. Found: C, 5(2.53; H, 4.55; N, 10.43.
3-(4-Chlorophenyl)-2-((3aÄ,5S,6S,6aÄ)-6-((1-(4-chlo-rophenyl)-1_ff-imidazol-4-yl)methoxy)-2,2-dimethylte-trahydrofuro[2,3-d][1,3]dioxol-5-yl)thiazolidin-4-one (8b). mp 216-218 °C; IR (KBr) v 3430, 3229, 2984, 2972, 2832, 1712, 1610, 1549, 1510, 1412, 1219, 682 cm-1; 1H NMR (300 MHz, CDCl3): 5 8.02 (s, 1H, Ar-H), 7.50 (d, J = 9.2 Hz, 4H, Ar-H), 73.41 (d, J = 8.9 Hz, 4H, Ar-H), 5.72 (d, J = 3.6 Hz, 1H, C1H), 4.94 (d, J = 5.2 Hz, CH-S), 4.60 (t, J = 3.9 Hz, 1H, C2H), 4.51 (s, 2H, OCH2), 3.96-3.91 (m, 1H, C4H), 3.76 (s,22H, CH2), 3.31 (dd, J2= 9.1, 4.2 Hz, 1H, C3H), 1.55 (s, 3H, CH3), 1.32 (m, 3H, CH3); 13C NMR (75MHz, CDCl3): 5 170.6, 139.4, 134.8, l3): 5 172.6, 143.2, 137.4, " 133.6, 132.3, 131.2, 128.4,
2-((3afl,5S,6S,6afl)-6-((H4-ChlorophenylM#-1,2,3-
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-(4-nitrophenyl)thiazolidin-4-one (8c). mp 201-205°C; IR (KBr) v 3432, 3226, 2982, 2971, 2830, 1710, 1608, 1546, 1512, 1414, 1374, 1216, 865, 632 cm-1; 1H NMR (300 MHz, CDCl3): 5 8.26 (d, J = 8.7 Hz, 2H), 8.04 (s, 1H, Ar-H), 7.51 (d, J = 9.2 Hz, 2H, Ar-H), 7.42 (d, J = 8.5 Hz, 2H, Ar-H), 6.82 (d, J = 9.8 Hz, 2H, Ar-H), 5.71 (d, J = 3.6 Hz, 1H, C1H), 4.96 (d, J = 5.2 Hz, CH-S), 4.62 (t, J = 3.9 Hz, 1H, C2H), 4.53 (s, 2H, OCH2), 3.96-3.91 (m, 1H, C4H), 3.76 (s, 2H, CH2), 3.28 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 1.52 (s, 3H, CH3), 1.34 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 170.6, 147.5, 144.4, 143.2, 134.8, 131.2, 128.6, 124.6, 122.4, 119.8, 111.8, 104.9, 81.5, 78.2, 74.8, 66.9, 52.4, 34.6, 26.8; MS: m/z (M++H) 574.10. Anal. Calcd for C^H^ClN^S: C, 52.31; H, 4.21; N, 12.20. Found: C, 52.265; H, 4.19; N, 12.11.
2-((3afl,5S,6S,6afl)-6-((H4-ChlorophenylM#-1,2,3-
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofu-ro[2,3-d][1,3]dioxol-5-yl)-3-0-tolylthiazolidin-4-one (8d). mp 181-183°C; IR (KBr) v 3436, 3234, 2986, 2976, 2834, 1710, 1705, 1610, 1549, 1516, 1418, 1262, 865 cm-1; 1H NMR (300 MHz, CDCl3): 5 8.23 (d, J = 8.7 Hz, 2H, Ar-H), 8.04 (s, 1H, Ar-H), 73.54 (d, J = 9.2 Hz, 2H, Ar-H), 7.45-6.82 (m, 5H, Ar-H), 5.74 (d, J = 3.6 Hz, 1H, C1H), 4.94 (d, J = 5.2 Hz, 1H, CH-S), 4.62 (t, J = 3.9 Hz, 1H, C2H), 4.54 (s, 2H, OCH2), 3.96-3.91 (m, 1H, C4H), 3.76 (s, 2H, CH2), 3.26 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 2.1 (s, 3H, CH3), 1.53 (s, 3H, CH3), 1.36 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 170.6, 144.6,
138.7,	134.8, 134.3, 130.6, 129.4, 128.6, 125.8, 122.6,
119.8,	111.6, 104.8, 81.7, 78.6, 74.7, 66.5, 52.4, 26.6, 16.5; MS: m/z (M++H) 545.10. Anal. Calcd for C^H^ClNPjS: C, 57.51; H, 5.51; N, 10.32. Found: C, 56.86; H, 5.39; N, 10.11.
2-((3afl,5S,6S,6afl)-6-((H4-ChlorophenylM#-1,2,3-
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-p-tolylthiazolidin-4-one (8e). mp
191-193°C; IR (KBr) v 3428, 3230, 2986, 2976, 2832, 1708, 1698, 1608, 1546, 1514, 1416, 1261, 859 cm-1; 1H NMR (300 MHz, CDCl3): 5 8.26 (d, J = 8.7 Hz, 2H, Ar-H), 8.04 (s, 1H, Ar-H), 7.54 (d, J = 9.2 Hz, 2H, Ar-H), 7.39 (d, J = 8.3 Hz, 2H, Ar-H), 7.15 (d, J = 8.3 Hz, 2H, Ar-H), 5.76 (d, J = 3.6 Hz, 1H, C1H), 4.96 (d, J = 5.2 Hz, 1H, CH-S), 4.66 (t, J = 3.9 Hz, 1H, C2H), 4.54 (s, 2H, OCH2), 3.96-3.91 (m, 1H, C4H), 3.76 (s, 2H, CH2), 3.26 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 2.30 (s, 3H, CH3), 1.53 (s, 3H, CH3), 1.36 (m, 3H, CH3); 13C NMR (75 MHz, CDC-
133.2, 129.4, 128.6, 125.6, 122.2, 119.4, 111.2, 104.9, 81.5, 74.5, 66.3, 52.6, 34.6, 26.5; MS: m/z (M++H) 563.10. Anal. Calcd for C25H24Cl2N4O5S: C, 53.29; H, 4.29; N, 9.94. Found: C, 53.21; H, 44.16; N, 9.83.
127.9, 124.8, 122.9, 119.2, 111.2, 103.8, 81.2, 78.1, 74.1, 65.9, 51.4, 26.1, 16.1; MS: m/z (M++Na) 565.10. Anal. Calcd for C26H27ClN4O5S: C, 57.51; H, 5.51; N, 10.32. Found: C, 5(5.82; H, 5.35; N, 10.09.
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2-((3afl,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-rf][1,3]dioxol-5-yl)-3-(3-hydroxyphenyl)thiazolidin-4-one (8f). mp 208-209°C; IR (KBr) v 3535, 3426, 3231, 2985, 2974, 2832, 1710, 1610, 1549, 1516, 1418, 1261, 864 cm1; 1H NMR (300 MHz, CDCl3): 5 8.26 (d, J = 8.7 Hz, 2H, Ar-H), 8.03 (s, 1H, Ar-H), 7.56 (d, J = 9.2 Hz, 2H, Ar-H), 7.14-6.70 (m, 4H, Ar-H), 5.76 (d, J = 3.6 Hz, 1H, C1H), 5.40 (s, 1H, OH), 4.96 (d, J = 5.2 Hz, 1H, CH-S), 4.66 (t, J = 3.9 Hz, 1H, C2H), 4.54 (s, 2H, OCH2), 3.93-3.96 (m, 1H, C4H), 3.74 (s, 2H, CH2), 3.26 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 1.53 (s, 3H, CH3), 1.38 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 171.6, 158.3, 144.2, 143.2, 134.6, 134.4, 130.6, 128.6, 122.2, 120.1, 119.4, 114.6, 111.8, 107.6, 106.8, 81.8, 78.6, 74.8, 64.9, 54.9, 41.1, 35.3; MS: m/z (M++H) 545.20. Anal. Calcd for C25H25ClN4O6S: C, 55.09; H, 4.62; N, 10.28. Found: C, 54.82; H, 4.55; N, 10.19.
2-((3afl,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-rf][1,3]dioxol-5-yl)-3-(4-hydroxyphenyl)thiazolidin-4-one (8g). mp 263-265°C; IR (KBr) v 3541, 3425, 3232, 2987, 2980, 2834, 1710, 1612, 1546, 1519, 1416, 1258, 862 cm-1; 1H NMR (300 MHz, CDCl3): 5 8.22 (d, J = 8.7 Hz, 2H, Ar-H), 8.06 (s, 1H, Ar-H), 7.54 (d, J = 9.2 Hz, 2H, Ar-H), 7.10-6.70 (m, 4H, Ar-H), 5.76 (d, J = 3.6 Hz, 1H, C1H), 5.28 (s, 1H, OH), 4.92 (d, J = 5.2 Hz, 1H, CH-S), 4.165 (t, J = 3.9 Hz, 1H, C2H), 4.52 (s, 2H, OCH2), 3.91-3.94 (m, 1H, C4H), 3.79 (s, 2H, CH2), 3.34 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 1.52 (s, 3H, CH3), 1.36 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 171.2, 157.8, 143.8, 143.2, 133.9, 133.4, 130.2, 127.6, 121.9, 120.5, 1198.8, 114.2, 111.2, 106.8, 81.4, 78.2, 73.8, 62.9, 54.2, 40.9, 34.9; MS: m/z (M++H) 545.20. Anal. Calcd for C25H25ClN4O6S: C, 55.09; H, 4.62; N, 10.28. Found: C, 5452; H, 4.596; N, 10.22.
2-(2-((3afl,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofu-ro[2,3-d][1,3]dioxol-5-yl)-4-oxo-3-phenylthiazolidin-5-yl)acetic acid (9 a-g). To a solution of diol 6 (0.200 g, 0.48 mmol) in CH2Cl2 (5 mL), NaIO4 (0.130 g, 0.61 mmol) was added at 0 °C and stirred at room temperature for 6 h. The reaction mixture was filtered and washed with CH2Cl2 (2 x 10 mL). It was dried (Na2SO4) and evaporated to give aldehyde 7 (0.150 g) in quantitative yield as a yellow liquid, which was used as such for the next reaction.
To a stirred mixture of 7 (0.150 g, 0.395 mmol), aromatic amine (0.395 mmol) and thiomalic acid (0.125 g, 0.86 mmol) in dry toluene (5 mL), anhydrous ZnCl2 (0.100 g, 0.751 mmol) was added after 2 min and irradiated in microwave bath reactor at 280 W for 4-7 min at 110 °C. After cooling, the filtrate was concentrated to dryness under reduced pressure and the residue was taken up in ethyl acetate. The ethyl acetate layer was washed with 5% sodium
bicarbonate solution and finally with brine. The organic layer was dried over Na2SO4 and evaporated to dryness at reduced pressure. The crude product thus obtained was purified by column chromatography on silica gel (60-120 mesh) with hexane-ethyl acetate as the eluent. Under conventional method the reaction mixture in toluene (10 mL) was refluxed at 110 °C for the appropriate time (Table 1).
2-(2-((3afl,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-
I,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofu-ro[2,3-d][1,3]dioxol-5-yl)-4-oxo-3-phenylthiazolidin-5-yl)acetic acid (9a). mp 211-214°C; IR (KBr) v 3436, 3226, 2984, 2973, 2942, 2832, 1724, 1614, 1549, 1510, 1412, 1224, 685 cm-1; 1H NMR (300 MHz, CDCl3): 5
II.44	(s, 1H, CO2H), 8.09 (s, 1H, Ar-H), 7.55 (d, J =3 9.2 Hz, 2H, Ar-H), 7.48 (d, J = 8.9 Hz, 2H, Ar-H), 6.73-7.35 (m, 5H, Ar-H), 6.15 (s, 1H, CHS), 5.73 (d, J = 4.2 Hz, 1H, C1H), 4.69 (t, J = 3.9 Hz, 1H, C2H), 4.65 (t, 1H, CH), 4.52 (s, 2H, OCH2), 3.92-3.89 (m, 1H, C4H), 3.31 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 2.38 (d, 2H, CH2), 1.53 (s, 3H, CH3), 1.30 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 170.9, 143.8, 141.2, 134.2, 128.2, 126.8, 122.1, 118.8, 104.2, 80.4, 77.9, 73.8, 66.1, 52.0, 37.2, 33.9, 25.9; MS: m/z (M++H) 545.20. Anal. Calcd for C27H27ClN4O7S: C, 55.24; H, 4.64; N, 9.54. Found: C, 55.12; H, 4.59; N, 9.39.
2-(3-(4-Chlorophenyl)-2-((3afl,5S,6S,6afl)-6-((1-(4-chlorophenyl)-1ff-1,2,3-triazol-4-yl)methoxy)-2,2-di-methyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-4-oxot-hiazolidin-5-yl)acetic acid (9b). mp 259-261 °C; IR (KBr) v 3438, 3431, 2982, 2829, 1724, 1716, 1608, 1539,
1509,	1410, 1216, 689 cm-1; 1H NMR (300 MHz, CDCl3): 5 11.44 (s, 1H, CO2H), 7.98 (s, 1H, Ar-H), 7.45 (d, J = 9.2 Hz, 4H, Ar-H), 7.39 (d, J = 8.9 Hz, 4H, Ar-H), 6.14 (s, 1H, CHS), 5.73 (d, J = 4.2 Hz, 1H, C1H), 4.69 (t, J = 3.9 Hz, 1H, C2H), 4.65 (t, 1H, CH), 4.52 (s, 2H, OCH2), 3.92-3.89 (m, 1H, C4H), 3.20 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 2.34 (d, 2H, CH2), 1.53 (s, 3H, CH3), 1.30 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 170.6, 143.2, 141.6, 134.6, 128.8, 126.9, 122.2, 118.4, 104.5, 80.6, 77.6, 73.2, 66.4, 52.3, 36.9, 33.2, 25.6; MS: m/z (M++H) 621.13. Anal. Calcd for C27H26Cl2N4O7S: C, 52.18; H, 4.22; N, 9.01. Found: C, 52^2; H, 4.09; N, 8.95
2-(2-((3aff,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-(4-nitrophenyl)-4-oxothiazolidin-5-yl)aceticacid (9c). mp 256-258 °C; IR (KBr) v 3428, 3434, 3225, 2981, 2966, 2820, 1725, 1710, 1609, 1536,
1510,	1412, 1373, 1210, 863, 639 cm-1; 1H NMR (300 MHz, CDCl3): 5 11.45 (s, 1H, CO2H), 8.21 (d, J = 8.4 Hz, 2H), 8.01 (s, 1H, Ar-H), 7.49 (d, J = 9.1 Hz, 2H, Ar-H), 7.41 (d, J = 8.5 Hz, 2H, Ar-H), 6,79 (d, J = 9.6 Hz, 2H, Ar-H), 6.14 (s, 1H, CHS), 5.69 (d, J = 4.2 Hz, 1H, C1H), 4.65 (t, 1H, CH), 4.53 (t, J = 3.9 Hz, 1H, C2H), 4.52 (s, 2H, OCH2), 3.90-3.86 (m, 1H, C4H), 3.19 (dd, J = 9.1, 4.2 Hz,
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1H, C3H), 2.30 (d, 2H, CH2), 1.49 (s, 3H, CH3), 1.25 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 190.2, 173.2, 143.6, 141.9, 134.5, 128.2, 126.5, 122.2,118.2, 104.3, 80.4, 77.2, 73.1, 66.2, 52.1, 36.4, 33.1, 25.4; MS: m/z (M++H) 632.13. Anal. Calcd for C27H26Cl2N5O9S: C, 51.31; H, 4.15; N, 11.08. Found: C, 51.19; H, 4.09; N, 10.95.
2-(2-((3afl,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofu-ro[2,3-d][1,3]dioxol-5-yl)-4-oxo-3-0-tolylthiazolidin-5-yl)acetic acid (9d). mp 247-249 °C; IR (KBr) v 3431, 3229, 2978, 2834, 1709, 1699, 1610, 1550, 1516, 1418, 1264, 853 cm-1; 1H NMR (300 MHz, CDCl3): 5 11.45 (s, 1H, CO2H), 8.22 (d, J = 8.4 Hz, 2H, Ar-H), 8.06 (s, 1H, Ar-H), 7.50 (d, J = 9.1 Hz, 2H, Ar-H), 7.42-6.85 (m, 4H, Ar-H), 6.14 (s, 1H, CHS), 5.65 (d, J = 4.2 Hz, 1H, C1H), 4.60 (t, 1H, CH), 4.53 (t, J = 3.9 Hz, 1H, C2H), 4.54 (s, 2H, OCH2), 3.92-3.86 (m, 1H, C4H), 3.22 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 2.34 (d, 2H, CH2), 2.21 (s, 3H, CH3), 1.51 (s, 3H, CH3), 1.29 (m, 3H, CH3); 13C NMR (753 MHz, CDCl3): 5 191.4, 173.4, 144.6, 142.9, 133.9, 125.4, 122.2, 119.2, 105.6, 80.6, 77.4, 73.4, 66.5, 53.1, 36.3, 33.2, 25.2, 16.2; MS: m/z (M++H) 600.13. Anal. Calcd for C28H29ClN4O7S: C, 55.95; H, 4.86; N, 9.32. Found: C, 54.19; H, 4.627; N, 9.15.
2-(2-((3afl,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofu-ro[2,3-d][1,3]dioxol-5-yl)-4-oxo-3-p-tolylthiazolidin-5-yl)aceticacid (9e). mp 197-199 °C; IR (KBr) v 3435, 3239, 2971, 2830, 1710, 1696, 1615, 1540, 1510, 1428, 1254, 843 cm-1; 1H NMR (300 MHz, CDCl3): 5 11.45 (s, 1H, CO2H), 8.20 (d, J = 8.4 Hz, 2H, Ar-H), 8.04 (s, 1H, Ar-H), 7.54 (d, J = 9.1 Hz, 2H, Ar-H), 7.36 (d, J = 8.3 Hz, 2H, Ar-H), 7.12 (d, J = 8.3 Hz, 2H, Ar-H), 6.14 (s, 1H, CHS), 5.65 (d, J = 4.2 Hz, 1H, C1H), 4.60 (t, 1H, CH), 4.53 (t, J = 3.9 Hz, 1H, C2H), 4.54 (s, 2H, OCH2), 3.92-3.86 (m, 1H, C4H), 3.22 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 2.34 (d, 2H, CH2), 2.21 (s, 3H, CH3), 1.51 (s, 3H, CH3), 1.29 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 191.4, 173.4, 144.6, 142.9, 133.9, 125.4, 122.2, 119.2, 105.6, 80.6, 77.4, 73.4, 66.5, 53.1, 36.3, 33.2, 25.2, 16.2; MS: m/z (M++H) 600.13. Anal. Calcd for C28H29ClN4O7S: C, 55.95; H, 4.86; N, 9.32. Found: C, 54.19; H, 4.62; N, 9.15.
2-(2-((3afl,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydro-furo[2,3-d][1,3]dioxol-5-yl)-3-(3-hydroxyphenyl)-4-oxothiazolidin-5-yl)acetic acid (9f). mp 227-229 °C; IR (KBr) v 3535, 3436, 3236, 2975, 2832, 1710, 1610, 1544, 1516, 1418, 1261, 864 cm-1; 1H NMR (300 MHz, CDCl3): 5 11.42 (s, 1H, CO2H), 8.24 (d, J = 8.7 Hz, 2H, Ar-H), 8.03 (s, 1H, Ar-H), 7.56 (d, J = 9.2 Hz, 2H, Ar-H), 7.14-6.70 (m, 4H, Ar-H), 6.14 (s, 1H, CHS), 5.76 (d, J = 3.6 Hz, 1H, C1H), 5.42 (s, 1H, OH), 4.96 (d, J =
5.2 Hz, 1H, CH), 4.51 (t, J = 3.9 Hz, 1H, C2H), 4.54 (s, 2H, OCH2), 3.93-3.96 (m, 1H, C4H), 3.26 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 2.34 (d, 2H, CH2), 1.53 (s, 3H, CH3), 1.38 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3): 5 175.6, 171.6, 158.3, 144.2, 143.2, 134.6, 134.4, 130.6, 128.6, 122.2, 120.1, 119.4, 114.6, 111.8, 107.6, 106.8, 81.8, 78.6, 74.8, 64.9, 54.9, 41.1, 38.9, 35.3; MS: m/z (M++H) 545.20. Anal. Calcd for C27H27ClN4O8S: C, 53.78; H, 4.52; N, 9.29. Found: C, 53.52; H, 4.35; N, 8.99.
2-(2-((3afl,5S,6S,6afl)-6-((1-(4-Chlorophenyl)-1tf-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofu-ro[2,3-d][1,3]dioxol-5-yl)-3-(4-hydroxyphenyl)-4-oxot-hiazolidin-5-yl)acetic acid (9g). mp 256-258 °C; IR (KBr) v 3532, 3430, 3226, 2973, 2830, 1710, 1616, 1534, 1506, 1411, 1258, 854 cm-1; 1H NMR (300 MHz, CDCl3): 5 11.39 (s, 1H, CO2H), 8.22 (d, J = 8.7 Hz, 2H, Ar-H), 8.06 (s, 1H, Ar-H), 7.52 (d, J = 9.2 Hz, 2H, Ar-H), 7.14-6.87 (m, 4H, Ar-H), 6.14 (s, 1H, CHS), 5.76 (d, J = 3.6 Hz, 1H, C1H), 5.42 (s, 1H, OH), 4.96 (d, J = 5.2 Hz, 1H, CH), 4.51 (t, J = 3.9 Hz, 1H, C2H), 4.54 (s, 2H, OCH2), 3.93-3.96 (m, 1H, C4H), 3.26 (dd, J = 9.1, 4.2 Hz, 1H, C3H), 2.34 (d, 2H, CH2), 1.53 (s, 3H, CH3), 1.38 (m, 3H, CH3); 13C NMR (775 MHz, CDCl3): 5 173.6, 171.6, 154.1, 143.2, 142.1, 133.6, 131.4, 129.6, 128.1, 122.6, 120.5, 115.4, 112.6, 111.8, 107.6, 106.8, 81.8, 78.6, 76.8, 65.9, 56.9, 42.1, 36.9, 34.3; MS: m/z (M++H) 545.20. Anal. Calcd for C27H27ClN4O8S: C, 53.78; H, 4.52; N, 9.29. Found: C, 53.42; H, 4.25; N, 8.79.
6. Conclusions
A series of novel triazole linked thiazolidenone derivatives 8a-g and 9a-g was prepared and evaluated for their antibacterial and nematicidal activity against various bacterias and nematodes. The screened compounds 8b, 9f exhibited potent antibacterial activity compared to standard drugs at the tested concentrations and 8f, 9f exhibited potent nematicidal activity compared to standard drugs at the tested concentrations.
7. Acknowledgements
The authors are thankful to CSIR - New Delhi for the financial support (Project funding No: 02(0247)15/ EMR - II), Director, CSIR - IICT, Hyderabad, India, for NMR and MS spectral analyses.
8. References
1. (a) K. D. Hanni, D. A. Leigh, Chem. Soc. Rev. 2010, 39, 1240-1251. http://dx.doi.org/10.1039/B901974J
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Povzetek
S pomočjo kondenzacije (3aR,5S,6^,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-di-methyltetrahydro[2,3-d][1,3]dioxole-5-carbaldehyde 7 z merkapto kislinami in primarnimi amini v prisotnosti ZnCl2 smo pod pogoji obsevanja z mikrovalovi in s klasičnim segrevanjem s pomočjo enolončnega postopka pripravili serijo novih derivatov 8a-g in 9a-g, ki vsebujejo povezana triazolski in tiazolidinonski obroč. Spojino 7 smo pripravili iz diaceton D-glukoze s pomočjo oksidacije, ki ji je sledila redukcija, klik reakcija, odščita primarnega acetonida in oksidativni razcep. Karakterizacijo novih spojin smo izvedli z IR, NMR, MS in elementno analizo. Raziskali smo tudi aktivnost novih spojin proti nematodam in bakterijam.
Srinivas et al.: Synthesis and Biological Evaluation