Levoglucosenone as a starting material for cascade continuous-flow synthesis of (R)-γ-carboxy-γ-butyrolactone.

The global imperative to shift towards renewable and sustainable resources has spurred significant interest in exploring and utilizing platform chemicals derived from renewable feedstocks. Among these, levoglucosenone (LGO) and Cyrene™ have emerged as promising candidates. LGO, derived from the pyrolysis of cellulose and hemicellulose, exhibits structural versatility, making it an attractive starting material for various valuable products.

Continuous Flow Synthesis of Hexyl Laurate Using Immobilized Thermomyces Lanuginosus Lipase from Residual Babassu Mesocarp.

Brazil has one of the greatest biodiversities on the planet, where various crops play a strategic role in the country's economy. Among the highly appreciated biomasses is babassu, whose oil extraction generates residual babassu mesocarp (BM), which still needs new strategies for valorization. This work aimed to use BM as a support for the immobilization of Thermomyces lanuginosus lipase (TLL) in an 8.

Batch and Continuous Flow Total Synthesis of Cannabidiol.

Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities.

Pharmacological potential of 4-dimethylamino chalcone against acute and neuropathic pain in mice.

Objectives: This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice.

Methods: The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC.

Developing Amphetamine Certified Reference Materials: From Batch and Continuous-Flow Synthesis to Certification Protocol.

Certified reference materials (CRM) of amphetamine derivatives were produced through a simple, rapid and efficient synthesis in both batch and continuous-flow conditions, accompanied by the development of a comprehensive certification protocol for this class of substances. Our chemistry enabled the synthesis of MDA, MDMA, PMA and PMMA in two steps from safrole and estragole with overall yields of 38-61 % in 48 hours under batch conditions and 61-65 % in 65 minutes under continuous-flow conditions, followed by the development of a certification protocol for these materials through identity checking, homogeneity, stability, and characterization studies. Furthermore, as result of this work, a very pure CRM of MDA.

Concise two-step chemical synthesis of molnupiravir.

A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale.

Lipase-catalyzed acylation of levoglucosan in continuous flow: antibacterial and biosurfactant studies.

Studies involving the transformation of lignocellulosic biomass into high value-added chemical products have been intensively conducted in recent years. Its matrix is mainly composed of cellulose, hemicellulose and lignin, being, therefore, an abundant and renewable source for obtaining several platform molecules, with levoglucosan (LG) standing out. This anhydrous carbohydrate can be acylated to obtain carbohydrate fatty acid esters (CFAEs).

Computer Modeling Explains the Structural Reasons for the Difference in Reactivity of Amine Transaminases Regarding Prochiral Methylketones.

Amine transaminases (ATAs) are pyridoxal-5'-phosphate (PLP)-dependent enzymes that catalyze the transfer of an amino group from an amino donor to an aldehyde and/or ketone. In the past decade, the enzymatic reductive amination of prochiral ketones catalyzed by ATAs has attracted the attention of researchers, and more traditional chemical routes were replaced by enzymatic ones in industrial manufacturing. In the present work, the influence of the presence of an α,β-unsaturated system in a methylketone model substrate was investigated, using a set of five wild-type ATAs, the ()-selective from (Atr-TA) and (Mva-TA), the ()-selective from (Cvi-TA), (Rpo-TA), (Vfl-TA) and an engineered variant of (ATA-256 from Codexis).

Lipases of Endophytic Fungi Stemphylium lycopersici and Sordaria sp.: Application in the synthesis of solketal derived Monoacylglycerols.

Monoacylglycerols (MAGs) are amphiphilic compounds with wide range of applications such as emulsifiers, solubility agents, and chiral building blocks. These compounds are currently produced by chemical approaches involving alkaline glycerolysis or esterification under high temperatures and pressure, resulting in low yields and with by-products. Lipase-catalyzed processes have been alternative tools to provide more ecological approaches since MAGs can be obtained under milder reaction conditions and with higher selectivity.

Cannabidiol Discovery and Synthesis-a Target-Oriented Analysis in Drug Production Processes.

The current state of evidence and recommendations for cannabidiol (CBD) and its health effects change the legal landscape and aim to destigmatize its phytotherapeutic research. Recently, some countries have included CBD as an antiepileptic product for compassionate use in children with refractory epilepsy. The growing demand for CBD has led to the need for high-purity cannabinoids on the emerging market.

Continuous-flow synthesis of dimethyl fumarate: a powerful small molecule for the treatment of psoriasis and multiple sclerosis.

Dimethyl fumarate (DMF) is a methyl ester of fumaric acid and has recently gained attention due to its use as a pro-drug in different pharmaceutical preparations, besides the low price of the final molecule and no active patents being available for the synthesis of DMF, the prices of multiple sclerosis treatment are still high. In our continuous effort for the development of process intensification strategies towards the synthesis of active pharmaceutical ingredients, here we present our work on a cascade methodology for dimethyl fumarate synthesis in short reaction times and quantitative yields.

Continuous-flow protocol for the synthesis of enantiomerically pure intermediates of anti epilepsy and anti tuberculosis active pharmaceutical ingredients.

Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks. In this work we developed two different strategies for the synthesis of intermediates used on the synthesis of levetiracetam/brivaracetam and ethambutol. The results obtained show that methionine methyl ester can be continuously converted to the desired ethambutol intermediate by RANEY® Nickel dessulfurization/reduction strategy whereas levetiracetam/brivaracetam intermediates could be synthesized by both RANEY® Nickel (without H2) and Pd/C-H2 approach or by photochemical desulfurization.

Combination of the Suzuki-Miyaura Cross-Coupling Reaction with Engineered Transaminases.

The combination of enzymatic and chemical reaction steps is one important area of research in organic synthesis, preferentially as cascade reactions in one-pot to improve total conversion and achieve high operational stability. Here, the combination of the Suzuki-Miyaura reaction is described to synthesize biaryl compounds followed by a transamination reaction. Careful optimization of the reaction conditions required for the chemo- and biocatalysis reaction enabled an efficient two-step-one-pot reaction yielding the final chiral amines with excellent optical purity (>99 % ee) in up to 84 % total conversion.

Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients.

We present a comprehensive review of the advent and impact of continuous flow chemistry with regard to the synthesis of natural products and drugs, important pharmaceutical products and definitely responsible for a revolution in modern healthcare. We detail the beginnings of modern drugs and the large scale batch mode of production, both chemical and microbiological. The introduction of modern continuous flow chemistry is then presented, both as a technological tool for enabling organic chemistry, and as a fundamental research endeavor.

Studies on the dynamic resolution of Crizotinib intermediate.

Crizotinib is an anti-cancer agent approved for treatment of non-small cell lung carcinoma. Retrosynthetic analysis revels 1-(2,6-dichloro-3-fluorophenyl)ethanol as an important intermediate, which can be made available by different biocatalytic approaches. Herein we report our results on the kinetic and dynamic resolution towards the desired chiral intermediate for Crizotinib synthesis.

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.

Nanoencapsulated Lecitase Ultra and Thermomyces lanuginosus Lipase, a Comparative Structural Study.

Two commercially available and widely used enzymes, the parent Thermomyces lanuginosus lipase (TLL) and the shuffled phospholipase A1 Lecitase (Lecitase Ultra), were encapsulated in AOT/isooctane reverse micelles and evaluated regarding their structure and activity. Preparations were also tested as effective biocatalysts. Small-angle X-ray scattering (SAXS), electronic paramagnetic resonance (EPR), and fluorescence spectroscopy were the techniques applied to assess the effects of enzyme incorporation to a reverse micellar nanostructure.

Functionalization of 2H-1,2,3-Triazole C-Nucleoside Template via N(2) Selective Arylation.

C-Nucleosides are an underexplored and important class of nucleosides with antiviral and anticancer activity. In addition, triazole heterocycles are well employed as a strategy to modify nucleobase in nucleoside analogues, although rare examples were described for triazoyl C-nucleosides. N(2)-Aryl-1,2,3-triazole C-nucleoside compounds that could be obtained by selective 1,2,3-triazole heterocycle N(2) arylation in 1-β-d-ribofuranosyl-2H-1,2,3-triazole substrate were designed in this study.

Bacillus amyloliquefaciens TSBSO 3.8, a biosurfactant-producing strain with biotechnological potential for microbial enhanced oil recovery.

A screening for biosurfactant-producing bacteria was conducted with 217 strains that were isolated from environmental samples contaminated with crude oil and/or petroleum derivatives. Although 19 promising biosurfactant producers were detected, strain TSBSO 3.8, which was identified by molecular methods as Bacillus amyloliquefaciens, drew attention for its production of a high-activity compound that presented an emulsification activity of 63% and considerably decreased surface (28.

Hydroxylation of 1,8-cineole by Mucor ramannianus and Aspergillus niger.

The monoterpenoid 1,8-cineole is obtained from the leaves of Eucalyptus globulus and it has important biological activities. It is a cheap natural substrate because it is a by-product of the Eucalyptus cultivation for wood and pulp production. In this study, it was evaluated the potential of three filamentous fungi in the biotransformation of 1,8-cineole.

Nanomicellar Formulation of Clotrimazole Improves Its Antitumor Action toward Human Breast Cancer Cells.

Background: Although demonstrated as a selective anticancer drug, the clinical use of clotrimazole (CTZ) is limited due to its low solubility in hydrophilic fluids. Thus, we prepared a water-soluble nanomicellar formulation of CTZ (nCTZ) and tested on the human breast cancer cell line MCF-7 biology.

Methodology/principal Findings: CTZ was nanoencapsulated in tween 80 micelles, which generated nanomicelles of, approximately, 17 nm of diameter.

New approaches on the analyses of thermolabile coffee diterpenes by gas chromatography and its relationship with cup quality.

A new gas chromatography method using pulsed split injector (PS-GC) was validated to quantify thermolabile diterpenes cafestol, kahweol and isokahweol in methanolysed Arabica coffee oils. Linearity was 0.99 from 8 to 69mgmL(-1), recovery ranged from 99% to 101% and precision of less than 4% was obtained.

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.

Stability and structural changes of horseradish peroxidase: microwave versus conventional heating treatment.

Effects of conventional heating (CH) and microwave (MW) on the structure and activity of horseradish peroxidase (HRP) in buffer solution were studied. CH incubation between 30 and 45 °C increased activity of HRP, reaching 170% of residual activity (RA) after 4-6 h at 45 °C. CH treatment at 50 and 60 °C caused HRP inactivation: RA was 5.