Home > Natural Isocoumarin Analogues, Functionalized Pyrazoles, N-Substituted Dihydropyridinones, Iminothiazolidinones, Iminothiazolines and Related Heterocycles: Synthesis and Characterization
Natural Isocoumarin Analogues, Functionalized Pyrazoles, N-Substituted Dihydropyridinones, Iminothiazolidinones, Iminothiazolines and Related Heterocycles: Synthesis and Characterization
The work presented in this thesis consists of synthesis and characterization of natural isocoumarin analogues and novel heterocyclic compounds. For convenience, the work has been divided into two parts, part one deals with the synthesis of various structural analogues of well known bioactive natural 3,4-dihydroisocoumarins viz. Annulatomarin, Montroumarin, Scorzocreticin, Typharin, and Hiburipyranone, along with the total synthesis of natural products 8-hydroxy-7-hydoxymethyl-6-methoxy-3,4- dihydroisochromen-1-one (Stellatin) and (±) 7-butyl-6,8-dihydroxy-3-pentyl-1H-3,4- dihydroisochromen-1-one have been carried out, starting from 3,5-dimethoxy-4-methyl homophthalic acid precursor. The synthesis of 3,5-dimethoxy-4-methylhomophthalic acid was carried out starting from commercially available p-toluic acid. It was then condensed with various aryl/alkyl acid chlorides to afford the corresponding 6,8-dimethoxy-7-methyl-3- aryl/alkylisochromen-1-ones (5a-j). These isochromen-1-ones were hydrolysed to keto- acids (6a-j) and then reduced to corresponding hydroxyacids, followed by cyclodehydration with acetic anhydride into corresponding 6,8-dimethoxy-7-methyl-3- aryl/alkyl-3,4-dihydroisochromen-1-ones (7a-j). Finally, demethylation of 3,4- dihydroisochromen-1-ones was carried out to afford 6,8-dihydroxy-7-methyl-3- aryl/alkyl-3,4-dihydroisochromen-1-ones (8a-j). Biological screening of all the synthesized compounds were carried out against ten bacterial strains, six were gram negative viz. Pseudomonas aeroginosa, Escherichia coli, Salmonella typhi, Shigella specie, Salmonella para typhi, Proteus mirabilis and four were gram positive viz Bacillus subtilus, Micrococcus aureus, Staphylococcus aureus and Streptococcus specie, bacterial strains, it was concluded that isochromen-1-ones (5a- j) and 3,4-dihydroisochromen-1-ones (7a-j) are more active against gram positive bacteria then gram negative. However, the 6,8-dihydroxy-3,4-dihydroisochromen-1-one derivatives (8a-j) are more active against gram negative then gram positive bacteria. Part two describes the synthesis of novel heterocyclic systems: functionalized pyrazoles, N-substituted dihydropyridinones, iminothiazolidinones and iminothiazolines. N-Methyl-3,4,5-tribromopyrazole was prepared by treating commercially available 3,4,5-tribromopyrazole with triethyl amine and methyl iodide indibromoethane. A variety of N-protected 3,4,5-triaryl-pyrazoles, 3,5-diaryl-4- bromopyrazoles, and 5-aryl-3,4-dibromopyrazoles were efficiently prepared by Suzuki Miyaura reactions. All the reactions were proceed with excellent site-selectivity with good yields. N-Substituted aza-bicyclo[3.1.0]hexan-1-ols were prepared via Kulinkovich reaction by treating titanium isopropoxide with variously substituted amino ester derivatives in anhy. Et 2 O/THF (1:1), followed by the addition of Grignard’s reagent (isopropylmagnesium bromide in ether). These bicyclo compounds were then stirred with the suspension of anhy. FeCl 3 in diethyl ether to afford dihydropyridinones in good yields. N-Substituted dihydropyridinones were subjected to [2+2] photochemically induced cycloaddition reactions, in order to explore the mechanism of unexpected rearranged product of N-benzyl dihydropyridinone while going through [2+2] photo cycloaddition reaction. 1-[Benzo[d]thiazol-2-yl)-3-(substituted] thioureas and ethyl 4-(3-benzoylthiour- eido) benzoates are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic compounds. These thioureas were converted into novel five membered heterocycles like methyl 2-[2-benzamido-3-(2-benzothiazolyl)-4-oxothia- zolidin-5-ylidene] acetates and ethyl 4-[2-benzamido-5-(2-methoxy-2-oxoethylidene)-4- oxothiazolidin-3-yl] benzoates in good yields, by the direct cyclization of these thioureas with dimethyl but-2-ynedioate (DMAD) in methanol. Ethyl 4-(3-benzoylthioureido) benzoates and 1-(benzo[d]thiazol-2-yl)-3- (substituted) thioureas serves as precursors for the synthesis of variety of biologically significant heterocyclic compounds like N-[3-(2-benzothiazolyl)-4-methylthiazol-2(3H)- ylidene] benzamides and N-[3-(benzo[d]thiazol-2-yl)-4-methylthiazol-2(3H)-ylidene] benzamides. These heterocycles were efficiently synthesized by the base-catalyzed cyclization of corresponding thioureas with 2-bromoacetone and triethylamine in moderate to good yields. Benzo[d]thiazol-2-amines, 1-(benzo[d]thiazol-2-yl)-3-(substituted) thioureas and ethyl 4-(3-benzoylthioureido) benzoates were examined in vitro for antibacterial activity against gram positive and gram negative bacteria and were found to exhibit good to potent activity as compared to the standard drugs. Benzo[d]thiazol-2-amines and 1- (benzo[d]thiazol-2-yl)-3-(substituted) thioureas were tested in vitro for their antifungalactivity against various fungal strains and were found to exhibit moderate activity as compared to the standard drug. The structures of all the synthesized compounds were confirmed by physical data, FTIR, 1 H NMR, 13 C NMR, mass spectrometry and elemental analysis.
منشی عبدالعزیز صاحب انصاری دارالمصنفین کے خیر خواہوں اور خدمت گزاروں کو یہ خبر سن کر بڑا رنج و غم اور سخت ملال ہوا کہ اس کی مجلس انتظامیہ کے ایک معزز، سرگرم، مخلص اور قدیم رکن جناب منشی عبدالعزیز صاحب انصاری یکم دسمبر کو بمبئی میں وفات پاگئے، اِناﷲِ وَ اِنا اِلَیہ رَاجِعُون، یہاں سے ان کا تعلق حضرت مولانا سید سلیمان ندویؒ کے دور میں قائم ہوا، جو بعد میں محکم سے محکم تر ہوتا گیا، وہ بمبئی میں رہتے تھے، لیکن ان کا وطن اعظم گڑھ ہی تھا، اس لیے دارالمصنفین سے ان کا بڑا گہرا قلبی اور جذباتی تعلق تھا۔ اکثر کہا کرتے تھے کہ اس نے ہماری عزت و شہرت میں چار چاند لگادیا ہے، اس سرزمین پر وہ لوگ چلتے پھرتے دکھائی دیتے ہیں جنھوں نے اس کو علم و فن کا لالہ زار بنادیا ہے، وہ اس کی مجلس انتظامیہ کے جلسوں میں نہایت پابندی سے تشریف لاتے، ان کے قیمتی مشوروں سے دارالمصنفین کو بڑا فائدہ پہنچتا، مشکل وقتوں میں اس کے لیے سینہ سپر رہتے، دارالمصنفین کو مالی اعانت کی ضرورت ہوتی تو اس کے کارکنوں کو بمبئی ملاتے اور اپنے یہاں دعوتوں پر اصحاب ثروت کو مدعو کرکے اس کی امداد کرنے پر آمادہ کرتے، شبلی کالج سے بھی خاص تعلق رکھتے اور اس کی ترقی سے بڑی دلچسپی لیتے، تقریباً چالیس برس سے اس کی مجلس انتظامیہ کے صدر تھے، ان کا انتخاب ہمیشہ بلامقابلہ ہوتا تھا۔ ان کی رسمی تعلیم زیادہ نہ تھی، لیکن بڑے علم دوست اور اردو فارسی کا اچھا ذوق رکھتے تھے، وہ بمبئی میں ٹرانسپورٹ کا کاروبار کرتے تھے، جہاں ایک سے بڑھ کر ایک تاجر تھے مگر جو عزت، نیک نامی اور قدر و منزلت انھوں نے حاصل کی وہ کم کسی کو نصیب ہوئی، وہ مہمانوں کے لیے ہر...
According to Islamic Jurists the main objectives, or purpose of Islamic Law (Shariah) are the preservation of faith, life, intellect, progeny, and wealth. These five purposes are designated as necessities of life and these are the primary purposes of the Shariah (Islamic Law). Protection of faith is the first and foremost objective of the Islamic Law as the Quran clearly mentions worship of Allah as the purpose of creation of human being. Protection of life is the second purpose and according to Islamic teachings human life is sacred. The Quran clearly forbids taking human life of a person without justification. Protection of Intellect is the third purpose as human being has been given superiority over other creatures by virtue of intellect and reason. A Person with sound mind and intellect can think, act, react well, this is why Islam prohibits all kinds of intoxicants because they are harmful and may disturb faculty of reasoning. Protection of Progeny is the fourth purpose as Islam emphasizes on the establishment of lawful relationship between man and woman. It is the foundation for the establishment of a value-based society. Islam considers unlawful relation harmful for individuals and community. This is the reason that Islam prohibits adultery. Protection of wealth is the fifth purpose and the Islamic teachings’ emphasis on acquisition of wealth by lawful means. While the Quran enjoins that one should not earn wealth by unlawful means. These dharurat (necessities are followed by the hajat (needs) and thasinat (complementary values). However the scope of these purposes goes beyond them and they include protection of civilization, culture, establishing peace, harmony, security, elimination of violence, maintenance of equality, and so on. In this article all these five kinds of dharurat (necessities) have been elaborated while in the last portion a review has been carried out for their relevance and implementation in the contemporary era.
Generally the information on the phytoplankton community occurring in the mangrove swamps at Sandspit backwaters (Pakistan) with considerable anthropogenic activities and influx of pollutants is lacking. The dearth of information has compelled to undertake the present study to assess the community structure of phytoplankton and its variability with respect to season and environmental conditions in Sandspit mangrove swamps. In addition, it was also aimed at the measurement of diatom growth in these polluted waters. The present study thus constitutes the first conclusive report on the ecology and chemistry of semiarid mangrove habitat of Sandspit back water at Karachi, Pakistan borders the northern Arabian Sea. In this research the distribution and diversity of marine phytoplankton are investigated. The results are presented as research chapters. The general introduction (Chapter 1) informs on the mangrove ecosystem and its importance on the coastal productivity. The research conducted in Pakistan in the planktonic community in the coastal waters is also summarized. The research summarizes that mangrove areas in the back waters of Karachi have particularly been ignored and a need to study phytoplankton and their behavior in the polluted mangrove environment is emphasized. The phytoplankton community occurring at the study site was assessed qualitatively and quantitatively (Chapter 2). Species of diatoms appeared to be more diverse and dominant as oppose to dinoflagellates which exhibited very low species diversity. Phytoplankton cell density varied seasonally and their abundance ranged from 0.25 x106-7.044x106 and 0.042x106-5.172x106 cells L‾1 during high and low tide, respectively. Pennate diatoms were highly diversified (23 taxa) as compare to centric diatoms (3 taxa). The low diversity and abundance of phytoplanktons is considered as the result of organic and inorganic pollution fluxed in through Layari River into the area. Chapter 3 presents diatom community composition and environmental variables affecting them in the mangrove ecosystem during summer and winter season, 2015. Centric diatoms were dominated by Cyclotella cf. menenghiana, whereas Cyilndrotheca closterium was the xvi most abundant species in pennate group (Chapter 2). The unfavorable conditions prevailing in the region appear to control low diversity and abundance of diatom species. As there exists no information with reference to their correlation with planktonic community, the present study was therefore carried out to assess the status of commonly polluting metals and pesticides in the sediment and water (Chapter 4) with an aim to present the current status of major components of effluent being fluxed in Sandspit backwaters through Layari and ascertain its influence on the distribution, abundance and diversity of phytoplankton. In this study seven metals (Cr, Cu, Fe, Hg, Mn, Pb, and Zn) were determined at high and low tidal conditions in water and sediments. Overall it was found that Fe and Mn had high concentrations and that Cu, Cr, Zn, Pband Hg maintained low concentrations. Generally, metal concentrations in in the area were found in the following order: Fe>Mn>Cu>Cr>Zn>Pb>Hg. The pollution/comtamination levels in the backwaters due to the Layri River input were assessed using different ecological tools, such as, Contimination factor (Cf), Ecological risk factor (Er) and Pollution load index (PLI). In water at both tidal conditions contamination factor (Cf) values of Cu and Pb were dominated over Cr and Zn and categorized as very high contamination. A comparison between stations for Cf showed preponderance of Cu at St 1 and Pb at St 2. The Cf values of all other metals indicate low contamination level at all stations. This is also evident from the data of PLI values which clearly show that the mangrove habitat in the study area is not as polluted as has been observed in the previous study from same habitat, except for St 1 where PLI was > 1 indicating polluted environment. The very high Rri mainly due to the Cu contamination in water at both high and low tides was noticed. However, no ecological risk in sediment was noted. The results thus endorse that this water body as significantly contaminated and therefore, accumulation of these metals may influence the aquatic life such as seen in case of phytoplankton abundance and diversity recorded in this study. The levels of organochlorine pesticides (OCPs) remained below detection limits though the area is generalviewed asheavilypolluted. Therefore it appears that bioaccumulation and transference of these chemicals from lower to higher trophic levels is not an issue in the area and that the low productivity may be influenced by metals and/or other environmental parameters. In Chapter V in-situ incubation experiments were conducted to assess the growth rate of the diatom community during winter at Sandspit backwater generally considered as polluted. Only a few pollution-resistant diatom species appear to grow in this habitat. A total of nine species were observed in the unfractionated (control) and fractionated samples. Growth rate of seven species were recorded ranging from -1.79 - 1.43 d-1 and 1.61 - 3.21 d-1 in unfractionated and fractionated samples, respectively. Average positive growth of diatom species, on the basis of cell abundance, was 0.8 d-1 in unfractionated (control) and 1.21 d-1 in fractionated samples.Positive growth was recorded for Coscinodiscus sp. (1.43 d-1), Navicula transitans var. derasa (1.39 d-1), C. cf. meneghiniana (0.37 d-1) and Cheaetoceros closterium (0.02 d-1) in unfractionated (control) samples, and Chaetoceros compressus (2.93 d-1), Cyclotella cf. meneghiniana (0.82 d-1), Coscinodiscus sp. (0.54 d-1), and Cylindrotheca closterium (0.53 d-1) in fractionated samples. Negative growth may be attributed to high grazing pressure or slow growth which fails to compete with grazing. The diatom diversity is low and the growth of many species is compromised in this polluted environment but the resistant species grow with the rates comparable to other species reported from cleaner waters.