Chemoenzymatic synthesis of duloxetine and its enantiomer: lipase-catalyzed resolution of 3-hydroxy-3-(2-thienyl) propanenitrile

An efficient and facile chemoenzymatic synthesis of duloxetine by lipase mediated resolution of 3-hydroxy-3-(2-thienyl)propanenitrile has been achieved. This process also describes an enantioconvergent synthesis of duloxetine via a Mitsunobu reaction.     

Green Synthetic Approach: An Efficient Eco-Friendly Tool for Synthesis of Biologically Active Oxadiazole Derivatives

Green synthetic protocol refers to the development of processes for the sustainable production of chemicals and materials. For the synthesis of various biologically active compounds, energy-efficient and environmentally benign processes are applied, such as microwave irradiation technology, ultrasound-mediated synthesis, photo-catalysis (ultraviolet, visible and infrared irradiation), molecular sieving, grinding and milling techniques, etc. Thesemethods are considered sustainable technology and become valuable green protocol to synthesize new drug molecules as theyprovidenumerous benefits over conventional synthetic methods.Based on this concept, oxadiazole derivatives are synthesized under microwave irradiation technique to reduce the formation of byproduct so that the product yield can be increased quantitatively in less reaction time. Hence, the synthesis of drug molecules under microwave irradiation follows a green chemistry approach that employs a set of principles to minimize or remove the utilization and production of hazardous toxic materials during the design, manufacture and application of chemical substances.This approach plays a major role in controlling environmental pollution by utilizing safer solvents, catalysts, suitable reaction conditions and thereby increases the atom economy and energy efficiency. Oxadiazole is a five-membered heterocyclic compound that possesses one oxygen and two nitrogen atoms in the ring system.Oxadiazole moiety is drawing considerable interest for the development of new drug candidates with potential therapeutic activities including antibacterial, antifungal, antiviral, anticonvulsant, anticancer, antimalarial, antitubercular, anti-asthmatic, antidepressant, antidiabetic, antioxidant, antiparkinsonian, analgesic and antiinflammatory, etc. This review focuses on different synthetic approaches of oxadiazole derivatives under microwave heating method and study of their various biological activities.     

Cyclopolymerization of N,N′-methylene bisacrylamide initiated by S2O82−–Fe2+ redox system

Polymerization of the symmetrical nonconjugated diolefin, N,N′-methylene bisacrylamide, was carried out using peroxodisulphate ion -Fe²⁺ as redox initiator. The rate of polymerization is found to depend on [M]^3/2 and [S₂O₈^2?]^1/2 and independent of [Fe²⁺] over a range. A polymerization mechanism involving cyclopolymerization in the propagation step is suggested. Evidence in favor of the cyclopolymerization mechanism is discussed. Evaluation of the rate parameters indicates that the deactivation of the primary radical SO₄^? by Fe²⁺ ion is a factor to be reckoned with.     

Studies on the reactivity of new types of tetracyclic‐1,5‐benzoxazepines: Part V

The syntheses of tetracyclic 1,5‐benzoxazepines 3a‐e from heterocyclic (3‐chloroaldehydes 1a‐e and 2‐aminophenol are reported herein (Scheme I). Attempted lithium aluminium hydride (LiAlH₄) reduction of the imine double bond in 3a‐e failed to furnish the corresponding saturated compounds 5a‐e. Attempted catalytic hydrogenation of 3a‐e in the presence of acetic acid and acetic anhydride gave surprisingly only the acetoxy derivatives 6a‐e in high yields (Scheme II). Base catalysed hydrolysis of acetoxy derivatives 6a‐e furnished, as expected, the corresponding phenolic derivatives 7a‐e , in moderate yields. Attempted cyclofunctionalization of 3a‐e either with mercaptoacetic acid or its methyl ester to obtain the new penta‐cyclic heterocycles 4a‐e was, however, not successful.     

Optimization of Levan Production by Cold-Active <Emphasis Type="Italic">Bacillus licheniformis</Emphasis> ANT 179 and Fructooligosaccharide Synthesis by Its Levansucrase

Fructooligosaccharides (FOS) and levan attract much attention due to a wide range of applications in food technology and pharmaceutical and cosmetic industry. Bacillus licheniformis ANT 179, isolated from Antarctica soil, produced levansucrase and levan in a medium containing sucrose as carbon substrate. In this study, characterization of levansucrase and production of short-chain FOS and levan were investigated. Temperature and pH optimum of the enzyme were found to be 60 °C and pH 6.0, respectively. The optimization of fermentation conditions for levan production using sugarcane juice by response surface methodology (RSM) was carried out. Central composite rotatable design was used to study the main and the interactive effects of medium components: sugarcane juice and casein peptone concentration on levan production by the bacterium. The optimized medium with sugarcane juice at 20 % (v/v) and casein peptone at 2 % (w/v) was found to be optimal at an initial pH of 7.0 and incubation temperature of 35 °C for 48 h. Under these conditions, the maximum levan concentration was 50.25 g/L on wet weight basis and 16.35 g/L on dry weight basis. The produced inulin type FOS (kestose and neokestose) and levan were characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) analysis. The study revealed that the levansucrase could form FOS from sucrose. The locally available low-cost substrate such as sugarcane juice in the form of a renewable substrate is proposed to be suitable even for scale-up production of enzyme and FOS for industrial applications. The levan and FOS synthesized by the bacterium are suitable for food applications and biomedical uses as the bacterium has GRAS status and devoid of endotoxin as compared to other Gram-negative bacteria.     

Chiral Recognition of Zolmitriptan by Modified Cyclodextrins

The two pyrrolidinylidenesulfamido‐modified β‐cyclodextrins (β‐CDs) 3 and 4 were prepared and studied for chiral discrimination of the enantiomers (R)‐ and (S)‐ 1 of zolmitriptan. The pyrrolidinylidenesulfamido spacer improved the chiral discrimination and binding abilities of these modified cyclodextrins. The hosts 3 and 4 showed higher selectivity for (S)‐ 1 . The association constants (Table) and enantioselectivity factors were calculated for the complexes of (R)‐ and (S)‐ 1 with the β‐CDs 2 – 4 . The formation of host?guest complexes was confirmed by ¹H‐NMR studies.     

Synthesis,anti‐bacterial,anti‐asthmatic and anti‐diabetic activities of novel N‐substituted‐2‐(benzo[d]isoxazol‐3‐ylmethyl)‐1H‐benzimidazoles

Synthesis of a series of novel class of N‐substituted‐2‐(benzo[d]isoxazol‐3‐ylmethyl)‐1H‐benzimidazoles ( 4 ) by the condensation of o‐phenylenediamine ( 1 ) with benzo[d]isoxazol‐3‐yl‐acetic acid ( 2 ) and subsequent reactions with different types of electrophiles have been reported. Some compounds exhibited promising anti‐bacterial activity against Salmonella typhimurium, however poor activity against Staphylococcus aureus. The compound 4t was found to have high activity even at 1 μg/ml compared to Cephalexin against S. aureus. The biological activity against PDE‐IV for potential anti‐asthmatic effect and against DP‐IV and PTP‐1B for potential anti‐diabetic effects was disappointing.     

Complementary Iron(II)‐Catalyzed Oxidative Transformations of Allenes with Different Oxidants

Substituent‐ and oxidant‐dependent transformations of allenes are described. Given the profound influence of the substituent on the reactivity of allenes, the subtle differences in allene structures are manifested in the formation of diverse products when reacted with different electrophiles/oxidants. In general, reactions of nonsilylated allenes involve an allylic cation intermediate by forming a C?O bond, at the sp‐hybridized C2, with either DDQ (2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone) or TBHP (tert‐butyl hydroperoxide), along with FeCl₂?4 H₂O (10 mol %). In contrast, silylated allenes favor the formation of propargylic cation intermediates by transferring the allenic hydride to the oxidant, thus generating 1,3‐enynes (E1 product) or propargylic THBP ethers (S_N1 product). The formation of these different putative cationic intermediates from nonsilylated and silylated allenes is strongly supported by DFT calculations.