1,1-enediamines and β-substituted enamines in heterocyclic synthesis

The work in this thesis mainly deals with l,l-enediamines and ~ -substituted enamines (push-pull olefines) and their reactions, leading to the formation of a number of heterocycles. Various ~-substituted enamines were prepared by a 'one pot synthesis' in which a l,l-enediamine presumably acts as an intermediate. These enamines, various substituted crotonamides and propenamides, were made by using two different orthoesters, various secondary and primary amines and cyanoacetamide. Their structures, mechanism of formation and geometry are discussed. A synthetic route to various unsymmetrically substituted pyridines was examined. Two substituted pyridinones were obtained by using two different ~-substituted enamines and cyanoacetamide. In one case a dihydropyridine was isolated. This dihydropyridine, on heating in acidic conditions, gave a pyridinone, which confirmed this dihydropyridine as an intermediate in this pyridine synthesis. A new synthetic method was used to make highly substituted pyridinones, which involved the reaction of l,l-enediamines with the ~-substituted enamines. A one pot synthesis and an interrupted one pot synthesis were used to make these pyridinones. Two different orthoesters and three different secondary amines were used. Serendipitous formation of a pyrimidinone was observed when pyrrolidine was used as the secondary amine and triethyl orthopropionate was used as the orthoester. In all cases cyanoacetamide was used as the carbon acid. This pyridine synthesis was designed with aI, l-enediamine as the Michael donor and the ~ -substituted enamines as Michael acceptors. Substituted ureas were obtained in two cases, which was a surprise. Some pyrimidines were made by reacting two substituted enamines with two different amidines. When benzamidine was used, the expected pyrimidines were obtained. But, when 2-benzyl-2-thiopseudourea (which is also an amidine) was used, of the two expected pyrimidines, only one was obtained. In the other case, an additional substitution reaction took place in which the S-benzyl group was lost. An approach to quinazolone and benzothiadiazine synthesis is discussed. Two compounds were made from 1, I-dimorpholinoethen

A case report: ruptured primary ovarian abscess in pregnancy

Primary ovarian abscess during pregnancy is a very rare entity.  The clinical presentation is very vague and hence can be a diagnostic dilemma. Diagnostic laparoscopy gives a definitive diagnosis and an opportunity to treat the entity in same settings. Herein we discussed a case of a ruptured primary ovarian abscess in pregnancy which was successfully managed by laparoscopy. Ovarian abscess is different from tubo-ovarian abscess. A delay in diagnosis may be associated with risk of maternal death and can be detrimental to the fetus also. Surgical drainage of ovarian abscess and conservative and minimally invasive surgical procedure under antibiotics are recommended during pregnancy

Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol [version 3; peer review: 1 approved, 2 approved with reservations]

Background In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. Methods In-silico molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and in vitro dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. Ex vivo permeation studies and in vivo pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Results Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. In-vitro dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the ex vivo and in vivo pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. Conclusions TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS

Enantioselective syntheses of aldohexoses using macrocyclic stereocontrol

A general method for enantioselective syntheses of aldohexoses using macrocyclic stereocontrol is described. The strategy employs simultaneous bis-dihydroxylation of chiral macrocyclic dienes to install the four contiguous stereogenic centers of aldohexoses. Conformational searches have been performed on two different macrocyclic precursors to the desired aldohexose using molecular mechanics calculations. Qualitative analysis of the low energy conformers obtained from these searches predicts L-gulose and D-idose, respectively, to be formed as major products in high enantiomeric ratios. The synthesis of the macrocyclic precursor to L-gulose was carried out in 5 steps from l-menthol. Key steps in this synthesis include a one-pot oxidation-Baeyer Villiger rearrangement of l-menthol and an intramolecular Horner-Wadsworth olefination to form a 14-membered ring in high yield. A broad survey of dihydroxylation conditions for osmylation of the diene was conducted. Although the majority of conditions resulted in complex mixtures of diastereomeric tetraols, catalytic OsO\sb4 and Me\sb3NO afforded two diastereomeric tetraols cleanly. Enantiomeric purity of the dihydroxylation products was determined through conversion of the macrocyclic tetraol to the corresponding hexitol hexaacetate and correlation with authentic material. The generality of this method was demonstrated by the synthesis of D-galactose from a related macrocycle using identical osmylation conditions

Application of experimental design and response surface technique for selecting the optimum RP-HPLC conditions for the determination of moxifloxacin HCl and ketorolac tromethamine in eye drops

A method has been developed for the separation of moxifloxacin HCl and ketorolac tromethamine using reverse phase high-performance liquid chromatography (RP-HPLC) on C18 column (250 × 4.6 mm, 5 μm) with UV detection at 308 nm. Experimental designs were applied for multivariate optimization of the experimental conditions of RP-HPLC method. Three independent factors: methanol content in the mobile phase composition, buffer pH and flow rate were used to design mathematical models. Here faced central composite (FCC) experimental design was used to study the response surface technique and to study in depth the effects of these independent factors. Derringer’s desirability function was applied to simultaneously optimize the retention time of last eluting peak (ketorolac tromethamine) and tailing factor of moxifloxacin. The predicted optimum assay condition consisted of methanol and potassium dihydrogen phosphate buffer (pH 3.2; 25 mM, 0.5% Triethylamine) in a proportion of 60:40% v/v, respectively, as the mobile phase at a flow rate of 1.2 mL min−1. Using this optimum condition, baseline separation of both drugs with good resolution and a run time of less than 7 min were achieved. The optimized assay condition was validated according to ICH guidelines to confirm specificity, linearity, accuracy and precision

SOLAR POWERED REFRIGERATION SYSTEM

Solar energy is proved to be ideal source for low temperature heating application .Three known approaches that use solar energy to provide refrigeration at temperature below 0 degrees include PV operated refrigeration solar mechanical and compression refrigeration both PV operated and solar mechanical cycle relay on vapor compression refrigeration cycle where as compression refrigeration uses thermal energy as the primary input to the cycle .among this three approaches PV system is the most viable and appropriate means for small capacity portable system located in area not near conventional energy resources

Estimation and Comparative Study of Operational Costs of Various Combined Tillage and Sowing Implements

Agricultural Engineer’s and economists use a variety of engineering and economic principles for calculating a machinery costs. An effective farm manager must also know these principles, and apply them when deciding to buy, lease, rent or share machinery. Thus, estimating farm machineries operational costs becomes essential to farmers for sound investment analysis and useful in planning, controlling production on their farms. Therefore, study was conducted to estimate and compare operational cost of various combined tillage and sowing implement namely Rotary Plough with Seed cum Fertilizer Drill, Till Planter, Roto Till Drill and Strip Till Drill at Vaugh Institute of Agricultural Engineering and Technology, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, (Uttar Pradesh) and period of study consumed about 2.5 years to complete the research activities. This present study concluded that operational cost of roto till drill and strip till drill was noted higher 796.57 Rs/hr and 791.66 Rs/hr, on the other side operational cost of rotary plough with seed drill and till planter was estimated lower 375.40 Rs/hr and 673.66 Rs/hr. The result also shows that operational cost of agricultural implements significantly depends on their initial cost. Therefore, roto till drill and strip till drill has higher operational cost because of their higher initial cost as compared to other combined tillage and sowing implements. Thus, implements subjected to higher initial cost tend to increase the operational cost