Multi-Catalytic Route for the Synthesis of (S)-Tembamide

Enantiopure β-amino alcohols constitute one of the most significant building blocks for the synthesis of active pharmaceutical ingredients. Despite the availability of a range of chiral β-amino alcohols from a chiral pool, there is a growing demand for new enantioselective synthetic routes to vicinal amino alcohols and their derivatives. In the present study, an asymmetric 2-step catalytic route that converts 4-anisaldehyde into a β-amino alcohol derivative, (S)-tembamide, with excellent enantiopurity (98% enantiomeric excess) has been developed. The recently published initial step consists in a concurrent biocatalytic cascade for the synthesis of (S)-4-methoxymandelonitrile benzoate. The O-benzoyl cyanohydrin is then converted to (S)-tembamide in a hydrogenation reaction catalyzed by Raney Ni. To achieve hydrogenation of the nitrile moiety with highest chemoselectivity and enantioretention, various parameters such as nature of the catalyst, reaction temperature and hydrogen pressure were studied. The reported strategy might be transferrable to the synthesis of other N-acyl-β-amino alcohols

Bioactivity in silica/poly(γ-glutamic acid) sol–gel hybrids through calcium chelation

Bioactive glasses and inorganic/organic hybrids have great potential as biomedical implant materials. Sol–gel hybrids with interpenetrating networks of silica and biodegradable polymers can combine the bioactive properties of a glass with the toughness of a polymer. However, traditional calcium sources such as calcium nitrate and calcium chloride are unsuitable for hybrids. In this study calcium was incorporated by chelation to the polymer component. The calcium salt form of poly(γ-glutamic acid) (γCaPGA) was synthesized for use as both a calcium source and as the biodegradable toughening component of the hybrids. Hybrids of 40 wt.% γCaPGA were successfully formed and had fine scale integration of Ca and Si ions, according to secondary ion mass spectrometry imaging, indicating a homogeneous distribution of organic and inorganic components. 29Si magic angle spinning nuclear magnetic resonance data demonstrated that the network connectivity was unaltered with changing polymer molecular weight, as there was no perturbation to the overall Si speciation and silica network formation. Upon immersion in simulated body fluid a hydroxycarbonate apatite surface layer formed on the hybrids within 1 week. The polymer molecular weight (Mw 30–120 kDa) affected the mechanical properties of the resulting hybrids, but all hybrids had large strains to failure, >26%, and compressive strengths, in excess of 300 MPa. The large strain to failure values showed that γCaPGA hybrids exhibited non-brittle behaviour whilst also incorporating calcium. Thus calcium incorporation by chelation to the polymer component is justified as a novel approach in hybrids for biomedical materials

Optimization of production, biochemical characterization and In Vitro evaluation of the therapeutic potential of fibrinolytic enzymes from a new Bacillus Amyloliquefaciens

The capacity of fibrinolytic enzymes to degrade blood clots makes them of high relevance in medicine and in the pharmaceutical industry. In this work, forty-three microorganisms of the genus Bacillus were evaluated for their potential to produce fibrinolytic proteases. Thirty bacteria were confirmed as producers of fibrinolytic enzymes, the best results obtained for the strain Bacillus amyloliquefaciens UFPEDA 485. The optimization of the enzyme production conditions was done by a central composite design (CCD) star 23 that allowed to define the optimal conditions for soybean flour and glucose concentrations and agitation rate. The highest fibrinolytic activity (FA) of 813 U mL-1 and a degradation of blood clot in vitro of 62% were obtained in a medium with 2% (w/v) of soybean flour and 1% (w/v) glucose at 200 rpm after 48 h of cultivation, at pH 7.2 and 37 °C. The obtained fibrinolytic enzyme was characterized biochemically. Fibrinolytic activity was inhibited by PMSF (fluoride methylphenylsulfonyl - C7H7FO2S) 91.52% and EDTA (ethylenediaminetetraacetic acid - C10H16N2O8) 89.4%, confirming to be a serine- metallo protease. The optimum pH and temperature were 7.0 and 37 oC, respectively, and the enzyme was stable for 12 h. The fibrinolytic activity at physiological conditions of this enzyme produced by Bacillus amyloliquefaciens UFPEDA 485, as well as its long term stability, demonstrate that it has suitable characteristics for human and veterinary applications, and promises to be a powerful drug for the treatment of vascular diseases.We express our thanks to Coordination for the Improvement of Higher Level Education Personnel (CAPES) - Doctoral Sandwich Program (PDSE) Nº 0259/ 12-8 and National Council for Scientific and Technological Development (CNPq) - Nº 202026/2011-6 for the financial support

Siderophore production by Bacillus megaterium : effect of growth-phase and cultural conditions

Siderophore production by Bacillus megaterium was detected, in an iron-deficient culture medium, during the exponential growth phase, prior to the sporulation, in the presence of glucose; these results suggested that the onset of siderophore production did not require glucose depletion and was not related with the sporulation. The siderophore production by B. megaterium was affected by the carbon source used. The growth on glycerol promoted the very high siderophore production (1,182 μmol g−1 dry weight biomass); the opposite effect was observed in the presence of mannose (251 μmol g−1 dry weight biomass). The growth in the presence of fructose, galactose, glucose, lactose, maltose or sucrose, originated similar concentrations of siderophore (546–842 μmol g−1 dry weight biomass). Aeration had a positive effect on the production of siderophore. Incubation of B. megaterium under static conditions delayed and reduced the growth and the production of siderophore, compared with the incubation in stirred conditions.The authors thank Porto University/Totta Bank for their financial support through the project "Microbiological production of chelating agents" (Ref: 180). The authors also thank the Fundacao para a Ciencia e a Tecnologia (FCT) through the Portuguese Government for their financial support of this work through the grants Strategic project-LA23/2013-2014 (IBB) and PEST-C/EQB/LA0006/2011 (REQUIMTE). Manuela D. Machado gratefully acknowledges the postdoctoral (SFRH/BPD/72816/2010) grant from FCT