Leandro S. M. Miranda

Lipases: Valuable catalysts for dynamic kinetic resolutions

Dynamic kinetic resolutions have proven to be a useful method for the preparation of enantiopure compounds from racemates, leading to the formation of a single enantiomer in theoretically 100% yield. Because lipases are ubiquitous, versatile, stereoselective and robust biocatalysts, they have been successfully applied as co-catalysts in these reactions, being mostly combined with metals in the chemoenzymatic dynamic kinetic resolutions of alcohols and amines.

Bio(chemo)technological strategies for biomass conversion into bioethanol and key carboxylic acids.

Biomass conversion into valuable compounds including fuels, chemicals and materials has become the subject of a wide range of studies in recent years. In spite of the several reports available on transformations of biomass-derived platform molecules into a range of products, chemo-catalytic and biotechnological strategies for the conversion of various feedstocks to key platform chemicals constitute an important area for biomass deconstruction which will allow subsequent processes for high added value products. This contribution has the objective of disclosing a series of strategies for the processing and pretreatment of key biomass feedstocks into platform chemicals, namely bioethanol and key carboxylic acids (e.g. levulinic and succinic acids).

A Retrosynthesis Approach for Biocatalysis in Organic Synthesis

For the planning of an organic synthesis route, the disconnection approach guided by retrosynthetic analysis of possible intermediates and the chemical reactions involved, back to ready available starting materials, is well established. In contrast, such concepts just get developed for biocatalytic routes. In this Review we highlight functional group interconversions catalyzed by enzymes. The article is organized rather by chemical bonds formed-exemplified for C-N, C-O- and C-C-bonds-and not by enzyme classes, covering a broad range of reactions to incorporate the desired functionality in the target molecule. Furthermore, the successful use of biocatalysts, also in combination with chemical steps, is exemplified for the synthesis of various drugs and advanced pharmaceutical intermediates such as Crispine A, Sitagliptin and Atorvastatin. This Review also provides some basic guidelines to choose the most appropriate enzyme for a targeted reaction keeping in mind aspects like commercial availability, cofactor-requirement, solvent tolerance, use of isolated enzymes or whole cell recombinant microorganisms aiming to assist organic chemists in the use of enzymes for synthetic applications.

Continuous flow valorization of fatty acid waste using silica-immobilized lipases

Silica immobilized lipases have been prepared and utilized in the valorization of fatty acid-derived food waste streams under continuous flow conditions. Findings demonstrate that better conversions could be obtained when compared with commercially available immobilized enzymes.

Ethyl acetate as an acyl donor in the continuous flow kinetic resolution of (±)-1-phenylethylamine catalyzed by lipases

The synthesis of chiral amines is still a challenge for organic synthesis since optically pure amines are of great importance for the pharmaceutical and agrochemical industries. Among all the methodologies developed until now, chemoenzymatic dynamic kinetic resolution has proven to be useful for the preparation of enantioenriched primary chiral amines. In our continuous efforts toward the development of a continuous flow process, herein we report our results on the continuous flow kinetic resolution of (±)-1-phenylethylamine leading to the desired products with high enantiomeric ratios (>200) and short residence times (40 minutes) using ethyl acetate as the acyl donor.

Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach

Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions. In this study, a series of forty synthetic chalcones was evaluated in vitro for their anti-inflammatory and antimycobacterial properties and in silico for pharmacokinetic parameters. Seven compounds strongly inhibited NO and PGE2 production by LPS-stimulated macrophages through the specific inhibition of iNOS and COX-2 expression, respectively, with compounds 4 and 5 standing out in this respect. Four of the seven most active compounds were able to inhibit production of TNF-α and IL-1β. Chalcones that were not toxic to cultured macrophages were tested for antimycobacterial activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb H37Rv strains in bacterial cultures and in infected macrophages. Four of them, including compounds 4 and 5, were active against a hypervirulent clinical Mtb isolate as well. In silico analysis of ADMET properties showed that the evaluated chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the obtained data demonstrate that at least two of the studied chalcones, compounds 4 and 5, are promising antimycobacterial and anti-inflammatory agents, especially focusing on an anti-tuberculosis dual treatment approach.

A Comprehensive Study on the Activity and Deactivation of Immobilized Lecitase Ultra in Esterifications of Food Waste Streams to Monoacylglycerols

Lecitase Ultra was immobilized on Amberlites XAD2 and XAD4, through physical entrapping under conventional stirring or ultrasound irradiation, and characterized by standard techniques. The resulting immobilized biocatalysts were utilized in the valorization of an acidic food-derived residue from a palm oil refining process to produce monoacylglycerols from isopropylidene glycerol under batch and continuous flow conditions. Results indicated that the immobilized biocatalysts could moderately convert the food waste residue (max. conversion 50-60 %), exhibiting interesting stability under continuous flow conditions.

A reação de ciclização de prins: uma estratégia eficiente para síntese estereosseletiva de anéis tetraidropirânicos substituídos

THE PRINS CYCLIZATION REACTION: AN EFFICIENT STRACTEGY FOR THE STEREOSELECTIVE SYNTHESIS OF SUBSTITUTED TETRAHYDROPYRAN RINGS. The Prins cyclization reaction has significantly advanced in the last years as demonstrated by a number of applications described in the literature. The objective of this report is to introduce this powerful synthetic methodology to the undergraduate and graduated student, since it is rarely presented in an organic synthesis formal course. This reaction is, in some cases, the methodology of choice for the preparation of natural products or drugs that present the tetrahydropyrane moiety in their structures. In this report we show some aspects of this reaction, including mechanism, scope and limitations.

Process intensification for tertiary amine catalyzed glycerol carbonate production: translating microwave irradiation to a continuous-flow process

Different products of interest can be produced from glycerol and glycerol carbonate (GC) has received much attention in recent years because of its physical properties, nontoxicity and water solubility. Herein we report a process intensification protocol for glycerol carbonate production mediated by tertiary amine catalysis where a 24 kg per L per day productivity was obtained with 79% isolated yield and a 5 hour operation time without losing efficiency.

Sporopollenin as an efficient green support for covalent immobilization of a lipase

Sporopollenin exine capsules (SECs), derived from the spores of Lycopodium clavatum, have been functionalised with 1,n-diamines and the resulting aminoalkyl microcapsules used to immobilize Candida antarctica lipase B (Cal B) via a glutaradehyde-based diimine covalent linker. The supported enzyme efficiently catalyzes the esterification of oleic acid with ethanol. Initial rates using the SEC-CalBs were comparable to the commercial enzyme Novozym 435, but displayed up to 20-fold higher specific activity. The supported enzymes could also be recycled and after four cycles displayed only a modest decrease in conversions. In a kinetic resolution the SEC-CalBs efficiently acetylated rac-1-phenylethanol, with conversions up to 37% after 5 hours and product enantiomeric excesses of >99%. Related to this, the dynamic resolution of rac-1-phenylethylamine, in the presence of Pd–BaSO4 and ammonium formate, led to the acetylated amine with a 94% conversion and >99% ee.