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.

Identification of Chalcone Derivatives as Inhibitors of Arginase and Promising Antileishmanial Agents.

Arginase catalyzes the hydrolysis of l-arginine into l-ornithine and urea, acting as a key enzyme in the biosynthesis of polyamines. growth and survival is dependent on polyamine biosynthesis; therefore, inhibition of arginase may be a promising therapeutic strategy. Here, we evaluated a series of thirty-six chalcone derivatives as potential inhibitors of arginase (LiARG).

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 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.

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.

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.

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.

Expanding the toolbox of asymmetric organocatalysis by continuous-flow process.

Despite all the organic chemistry reaction methodologies already developed for the continuous-flow process, asymmetric synthesis is one that has gained less attention. Since the pioneering work of Barbas and MacMillan, organocatalysis has emerged as the third pillar of asymmetric catalysis. In this review, we present a survey of literature regarding the use of organocatalysis under continuous-flow conditions.

Active pharmaceutical ingredients for antiretroviral treatment in low- and middle-income countries: a survey.

Active pharmaceutical ingredients (APIs) are the molecular entities that exert the therapeutic effects of medicines. This article provides an overview of the major APIs that are entered into antiretroviral therapy (ART), outlines how APIs are manufactured, and examines the regulatory and cost frameworks of manufacturing ART APIs used in low- and middle-income countries (LMICs). Almost all APIs for ART are prepared by chemical synthesis.

Continuous flow synthesis of α-halo ketones: essential building blocks of antiretroviral agents.

The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor.

A three step continuous flow synthesis of the biaryl unit of the HIV protease inhibitor Atazanavir.

The development of multistep continuous flow reactions for the synthesis of important intermediates for the pharmaceutical industry is still a significant challenge. In the present contribution the biaryl-hydrazine unit of Atazanavir, an important HIV protease inhibitor, was prepared in a three-step continuous flow sequence in 74% overall yield. The synthesis involved Pd-catalyzed Suzuki–Miyaura cross-coupling, followed by hydrazone formation and a subsequent hydrogenation step, and additionally incorporates a liquid–liquid extraction step.

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.

The antinociceptive properties of the novel compound (±)-trans-4-hydroxy-6-propyl-1-oxocyclohexan-2-one in acute pain in mice.

The compound (±)-trans-4-hydroxy-6-propyl-1-oxocyclohexan-2-one [(±)-δ-lactone] was isolated from the plant Vitex cymosa Bertero, and determined to be the active principle. The present study aimed to evaluate the antinociceptive effect of (±)-δ-lactone and to elucidate its mechanism of action. Mice were subjected to in-vivo models of acute pain (acetic acid-induced abdominal writhing, formalin and hot-plate tests) and the open-field test.

On the mechanism of the Dakin-West reaction.

The mechanism of the Dakin-West reaction has been thoroughly investigated by monitoring the reaction using ESI-MS/MS techniques in combination with M06-2X/6-311++G(d,p) calculations. Several of the key intermediates in the previously proposed "azlactone" mechanism have been experimentally detected and characterized. In particular, interception of the mixed anhydrides involved in the early and late stages of the mechanistic scheme, as well as of the cyclic acyl-oxazolone intermediate, supports the original pathway suggested by Dakin and West.

Antinociceptive activity of (-)-(2S,6S)-(6-ethyl-tetrahydropyran-2-yl)-formic acid on acute pain in mice.

Pain is a major cause of distress, both physical and psychological. There is a continuous search for new pharmacologically active analgesic agents with minor adverse effects. Recently, the synthesis of (-)-(2S,6S)-(6-ethyl-tetrahydropyran-2-yl)-formic acid [tetrahydropyran derivative (TD)] was described.

Antinociceptive action of (+/-)-cis-(6-ethyl-tetrahydropyran-2-yl)-formic acid in mice.

The objective of this study was to investigate spinal and supraspinal antinociceptive effects of a new synthetic compound, (+/-)-cis-(6-ethyl-tetrahydropyran-2-yl)-formic acid (tetrahydropyran derivative). Its activity was compared with those from morphine. In peripheral models of inflammation and hyperalgesia, tetrahydropyran derivative significantly reduced nociceptive effect induced by acetic acid or formalin in mice.