Theses and dissertations (Applied Sciences)
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Item Synthesis, characterization and biological activities of hererocycles : peptides, O, N, and S based small molecules(2018) Thangaraj, Muthu; Gengan, Robert MoonsamyThis study is based on the synthesis and characterization of quinoline based peptides and heterocycles containing oxygen, nitrogen and sulfur atoms by using new catalysts. In addition, the biological activities of the novel small molecules is evaluated. A total of 71 small molecules were prepared by using multi-component reactions including Ugi and Kabachnik-Fields reaction. The Ugi four-component reaction was implemented for the synthesis of medicinally important 13 new quinolinyl-lipoyl peptides (QLPs) and one quinolonyl-lipoyl peptide (QOLP) by microwave irradiation using methanol as medium. A series of 12 new quinolinyl-4H-pyrans (QPs), two quinolonyl-4H-pyrans (QOPs) and one indolyl-4H-pyran (IP) were successfully synthesized via a three-component reaction using ethanol as solvent in the presence of a new catalyst: humic acid supported 1-butyl- 3-methylimidazolium thiocyanate ionic liquid catalyst (HASIL) under microwave irradiation. By using Kabachnik-Fields reaction, a total of 14 novel α-aminobenzylthio- quinolinyl phosphonates (BTQPs) were synthesized in the presence of a catalytic amount of iron-loaded boron nitride (Fe/BN) catalyst by using water as medium. A series of 14 novel benzylthioquinolinyl-1,4-dihydropyridines (BTQ-DHPs) were synthesized with high yields in short reaction time by a four-component reaction in the presence of iodine- loaded boron nitride (I/BN) catalyst by using water as solvent. A total of 14 derivatives of 2-amino-4H-pyran-3-carbonitrile derivatives (APCs) were prepared by using calcium loaded boron nitride (Ca/BN) in ethanol as solvent. This transformation transpired via a Knoevenagel condensation, Michael addition and intra-molecular cyclization. The prepared catalysts: HASIL, Fe/BN, I/BN and Ca/BN were characterized by XRD, SEM with EDX, TEM, DSC, TGA, BET, Raman spectra and FTIR analysis. All the synthesized molecules (QLPs, QOLP, QPs, QOPs, IP, BTQPs, BTQ-DHPs and APCs) were confirmed by FTIR, 1H-NMR, 13C-NMR and elemental analysis. Moreover, 19F- NMR, 31P-NMR and TOF-MS analysis were included for some selected compounds. In every chapter, one model compound was selected and discussed with two-dimensional spectra such as HSQC, DEPT 90º, DEPT 135º (selected), COSY, NOESY and HMBC. Among the synthesized compounds, a total of 48 compounds (8 QLPs, 15 (QPs, QOPs and IP), 10 BTQPs, 10 BTQ-DHPs and 5 APCs) were subjected to antimicrobial activities with Bacillus cereus, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Candida albicans and Candida utilis and antioxidant studies were observed by the radical scavenging assay. The toxicity studies were evaluated using the brine shrimp assay and the mortality rate was noted. Among them, 4 peptides, 7 pyrans, 8 aminophosphonates, 7 dihydropyridines and 5 carbonitriles showed good antimicrobial activity whilst 3 peptides, 9 pyrans, 6 aminophosphonates and 4 dihydropyridines showed antioxidant potential. Also, 4 peptides, 5 pyrans, 8 aminophosphonates and 5 dihdyropyridines showed mortality rate less than 50 % upto 48 h. The molecular docking studies were performed by Libdock score with DNA gyrase, Mtb gyrase and Staphylococcus aureus gyrase. A docking score of 183.24 kcal/mol and 165.01 kcal/mol were recorded for 2 peptides compared to ciprofloxacin. Among quinolinyl pyrans, one QP showed higher binding affinity of 96.96 kcal/mol with Mtb DNA gyrase. One BTQP showed more potency towards Staphylococcus aureus gyrase with 149.97 kcal/mol and one BTQ-DHP showed a strong ligand-protein interaction toward Staphylococcus aureus gyrase with Libdock score of 125.27 kcal/mol. The advantages of the synthetic methodology of this project are its green approach, easy work up, mild reaction conditions, the use of an inexpensive solvent, short reaction times with higher yields and recyclability of the catalyst.Item Solvent-free Knoevenagel condensation over supported mixed metal oxides catalysts(2017) Makhanya, Nokubonga Prudence; Singh, Sooboo; Mabaso, M.H.Knoevenagel condensation reaction is a useful protocol for the formation of C=C bond in organic synthesis. This protocol is extensively utilized by synthetic chemist to generate dynamic intermediates or end-products such as perfumes, polymers, pharmaceuticals and calcium antagonists. The reaction is catalyzed by bases such as ammonia, primary and secondary amines, quaternary ammonium salts, Lewis acids, catalysts containing acid-base sites, which are carried out under homogeneous conditions. This necessitates the use of organic solvent which generate the large volumes of solvent waste. From green chemistry perspective, solvent free heterogeneous catalysts have received considerable attention. Since, these heterogeneous catalysts not only avoid the use of organic solvents but also suppress side reactions such as self-condensation and oligomerisation leading in better selectivity and product yield. In recent years, therefore, the use of heterogeneous catalyst, their recovery and reusability are in demand in industry. The use of cobalt, iridium and platinum hydroxyapatites, MgO/ZrO2, MgO/HMCM- earlier been reported in the literature, and used as heterogeneous catalysts for the Knoevenagel condensation of aldehydes and esters. Based on these evidences, we envisioned that MgO and VMgO could also be used as heterogeneous catalysts for this reaction. Magnesium oxide was synthesized from three precursors, viz. magnesium nitrate, magnesium carbonate and magnesium acetate. Magnesium oxide prepared from magnesium nitrate precursor was found to be the optimum giving an 81 % product yield. Vanadium-magnesium oxide catalysts with different vanadium loadings; 1.5, 3.5 and 5.5 wt. %, were synthesized by wet impregnation of magnesium oxide with aqueous ammonium metavanadate solution. The synthesized catalysts were characterized by ICP-AES, FTIR, Powder XRD, SEM-EDX and TEM. The Knoevenagel condensation reactions between benzaldehyde and ethyl cyanoacetate were carried out in a 100 mL two-necked round bottom flask equipped with a reflux condenser, magnetic stirrer and a CaCl2 guard tube. An equimolar quantity (10 mmol) of substrates and 0.05g of catalyst were added to the flask and heated at 60 °C, stirred vigorously for the required time. The yields were determined using GC-FID equipped with a capillary column. Elemental composition of the catalysts (vanadium and MgO) was determined by ICP-AES. IR spectra of MgO showed that magnesium oxide was the only phase present in the catalysts prepared from different precursors. The 1.5 and 5.5 wt. % VMgO showed weak bands attributed to pyrovanadate and orthovanadate phases present in small quantities. The phases manifested more with the increase in the vanadium concentration (3.5 and 5.5 wt. % VMgO). The diffraction patterns of all the catalysts showed the existence of MgO and magnesium orthovanadate. The morphology of the catalysts with increasing vanadium was more affected by precursor treatment rather than chemical differences. Electron microscopy showed that the VMgO surface is only sparingly covered with vanadium and MgO showed stacked with large rounded particles. Good to excellent yields were obtained for the MgO catalysts: MgO(1) 68 %, MgO(2) 65 %, MgO(3) 72 %, MgO(P) 73 % and MgO(DP) 82 %. Excellent yields were obtained for the VMgO catalysts: 1.5VMgO 83 %, 3.5VMgO 91 % and 5.5VMgO 97 %. The 5.5VMgO catalyst was found to be the optimum catalyst and was further tested for it activity using different aldehyde substrates. Excellent yields of the products were obtained for benzaldehyde 97 %, nitrobenzaldehyde 94 %, bromobenzaldehyde 96 %, chlorobenzaldehyde 93 % and methoxybenzaldehyde 95%.