Abstract In the current work, suitability of hyperbranched polyglycerol as a high loading catalyst support is demonstrated. A polyglycerol‐supported manganese‐salen complex (chemzyme) is applied as a homogeneous catalyst in the epoxidation of 6‐cyano‐2,2‐dimethylchromene. The recyclability of the corresponding catalyst was investigated in repetitive batch experiments as well as a continuous operation of the reaction in an ultrafiltration membrane reactor. An enhanced stability of the catalyst in repetitive batches was observed as a result of immobilization whereby the total turnover number increased from 23 in a single batch to 80 in four repetitive batches. To enable continuous operation, a continuously operated, stirred tanked reactor (CSTR) was equipped with an ultrafiltration membrane (MPF‐50) and a retention of 98% was determined. The continuous chemzyme membrane reactor was operated over the course of 20 residence times. After approximately 12 residence times, the steady state was reached yielding 70% conversion as well as an enantiomeric excess up to 92%. A space‐time yield (sty) of 458 g L −1 d −1 and a turnover frequency (TOF reaction ) of up to 18 h −1 was reached in the steady state. It was determined that the total turnover number (TTN) was enhanced by a factor of 10 from 24 (batch) up to 240 for 20 residence times in CSTR operation.
A suitable pharmacological substitute for the well-established surgical delay technique for axial skin flaps regarding increasing viability is elusive. We aimed to evaluate the effects of botulinum toxin type A (BTA) on the axial skin flap survival in a rat model.The present controlled experimental study was performed in Kerman University of Medical Science, Kermanshah, Iran during 2016-2017 on three groups of rats. Group 1 (control group) had no preconditioning while Groups 2 and 3 were preconditioned by the intradermal injection of normal saline (0.5 ml) in the cephalic end of the skin flap and the injection of the BTA (1.6 units Neuronex) reconstituted in normal saline, respectively. Two weeks after this intervention in each group, the flap was raised and kept in situ and a biopsy was simultaneously taken for evaluating neoangiogenesis, followed by evaluating flap necrosis after two weeks of following-up by photography.Although BTA induced angiogenesis significantly, it failed to reduce the area of necrosis compared to the other groups.BTA was effective in increasing angiogenesis in the axial skin flap although it was unable to reduce necrosis.
Asymmetric mixed carboligation reactions of α-ketoglutarate with different aldehydes were explored with the thiamine diphosphate dependent enzymes SucA from E. coli, Kgd from Mycobacterium tuberculosis, and MenD from E. coli. All three enzymes proved to be efficient biocatalysts to selectively deliver chiral δ-hydroxy-γ-keto acids with moderate to excellent stereoselectivity. The high regioselectivity is due to the preserved role of α-ketoglutarate as acyl donor for these enzyme-catalyzed reactions.
Abstract In this contribution, the facile synthesis of two new polymer‐supported 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) catalysts and their application in the catalytic oxidation of alcohols to carbonyl compounds are described. For attachment of the TEMPO group to the polymer an isocyanate functionalized polymer is chosen. This new approach facilitates the synthesis in comparison with previously existing methods which generally require deprotonation of TEMPO prior to reaction with the polymer. Following this approach, polyurethane (PU)‐ and polystyrene (PS)‐based TEMPO catalysts are prepared in a one‐step reaction from commercially available compounds. Both polymer‐supported catalysts showed promising yields for a variety of substrates using inorganic and/or organic co‐oxidants in biphasic and/or monophasic systems. The recyclability of the corresponding catalysts was studied in repetitive batch experiments using filtration or distillation depending on the support type. Furthermore, application of the homogeneous polyurethane‐supported TEMPO for the selective oxidation of benzyl alcohol in a continously operated membrane reactor is demonstrated.
We report the first rationally designed (S)-selective MenD from E. coli for the synthesis of functionalized α-hydroxy ketones. By mutation of two amino acids in the active site stereoselectivity of the (R)-selective EcMenD (ee > 93%) was inverted giving access to (S)-5-hydroxy-4-oxo-5-phenylpentanoate derivatives with stereoselectivities up to 97% ee.
The catalytic asymmetric synthesis of chiral 2-hydroxy ketones by using different thiamine diphosphate dependent enzymes, namely benzaldehyde lyase from Pseudomonas fluorescens (PfBAL), a variant of benzoylformate decarboxylase from Pseudomonas putida (PpBFD-L461A), branched-chain 2-keto acid decarboxylase from Lactococcus lactis (LlKdcA) and a variant of pyruvate decarboxylase from Acetobacter pasteurianus (ApPDC-E469G), was studied. Starting with the same set of substrates, substituted benzaldehydes in combination with different aliphatic aldehydes, PfBAL and PpBFD-L461A selectively deliver the (R)- and (S)-2-hydroxy-propiophenone derivatives, respectively. The (R)- and (S)-phenylacetylcarbinol (1-hydroxy-1-phenylacetone) derivatives are accessible in a similar way using LlKdcA and ApPDC-E469G, respectively. In many cases excellent stereochemical purities (>98 % enantiomeric excess) could be achieved. Hence, the regio- and stereochemistry of the product in the asymmetric aliphatic-aromatic cross-benzoin reaction can be controlled solely by choice of the appropriate enzyme or enzyme variant.
The thiamine diphosphate (ThDP) dependent MenD catalyzes the reaction of α-ketoglutarate with pyruvate to selectively form 4-hydroxy-5-oxohexanoic acid 2, which seems to be inconsistent with the assumed acyl donor role of the physiological substrate α-KG. In contrast the reaction of α-ketoglutarate with acetaldehyde gives exclusively the expected 5-hydroxy-4-oxo regioisomer 1. These reactions were studied by NMR and CD spectroscopy, which revealed that with pyruvate the observed regioselectivity is due to the rearrangement–decarboxylation of the initially formed α-hydroxy-β-keto acid rather than a donor–acceptor substrate role variation. Further experiments with other ThDP-dependent enzymes, YerE, SucA, and CDH, verified that this degenerate decarboxylation can be linked to the reduced enantioselectivity of acyloins often observed in ThDP-dependent enzymatic transformations.
Background: Orally disintegrating tablets (ODTs) are a modern form of tablets that when placed in the oral cavity, disperses rapidly. These tablets have advantages, particularly good applications for children and old patients who have a complication in chewing or swallowing solid dosage forms. The aim of this study was to design, formulate, and evaluate the physicochemical properties of 5 mg montelukast ODTs for the prevention of asthma and seasonal allergies. Methods: Formulations were prepared with different amounts of super disintegrating agents and effervescent bases as disintegrant agents. Flowability and compressibility of mixed powders were evaluated. The prepared formulations were tested for hardness, thickness, friability, weight variation, drug content, wetting time, disintegration time, dissolution study, and moisture uptake studies. Results: The compressibility index and angle of repose were in the range of 15.87%-23.43% and 32.93-34.65, respectively. Hardness, thickness, friability, wetting time, and content uniformity of formulations were in the range of 33.7-37.1 N, 3.00-3.81 mm, 0.27%-0.43%, 31-50 s and 96.28%-99.90%, respectively. Disintegration time of the tablets prepared with super disintegrating agents, effervescent bases, and combination of two were in the range of 30-50, more than 60 and 20-36 s, respectively.Conclusions: Mixture of powders and tablets passed all the specified tests. The results showed formulations prepared by super disintegrating agents and super disintegrating agents with effervescent bases had shorter disintegration time compared to formulations with effervescent bases alone.
The polyurethane-supported TEMPO (PU-TEMPO) 3 was prepared by treatment of Desmodur 1 with 4-hydroxy-TEMPO 2 in dimethylformamide. Immobilization of 2 on polystyrene (PS) supports was performed by mixing PS methyl isocyanate 4 and 2 upon heating to afford polystyrene-supported TEMPO (PS-TEMPO) 5. Oxidation of alcohols 6 was carried out with 3 or 5 in the presence of NaOCl (conditions A) or PhI(OAc)2 (conditions B) as a co-oxidant to give the corresponding carbonyl compounds 7 in up to 95% yield.
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