Rodrigo O. M. A. de Souza

• PhD Organic Chemistry
• Professor at Federal University of Rio de Janeiro

Pharmaceuticals and bioactive molecules often contain chiral pyrrolidines and azepanes as key structural elements. Traditional synthesis methods involve expensive catalysts and multiple steps. More efficient, selective, and environmentally friendlier synthetic routes are needed to improve accessibility to these valuable building blocks. This study...

Chiral heterocyclic alcohols and amines are frequently used building blocks in the synthesis of fine chemicals and pharmaceuticals. Herein, we report a one-pot photoenzymatic synthesis route for N-Boc-3-amino/hydroxy-pyrrolidine and N-Boc-4-amino/hydroxy-azepane with up to 90% conversions and >99% enantiomeric excess. The transformation combines a...

This study introduces a novel chemo-enzymatic cascade methodology for the sustainable conversion of canola oil into fuel-like hydrocarbons, combining biocatalysis and continuous-flow technology. The proposed approach addresses the urgent need for renewable energy sources by leveraging the enzymatic hydrolysis of canola oil using Candida rugosa lipa...

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 str...

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 immobiliz...

Pralidoxime salts are important medical countermeasures towards different organophosphorus compounds, either nerve agents or pesticides, as they act as acetylcholinesterase reactivators, avoiding health issues and even death that can result from intoxication with such chemicals. In this work, we present an expeditious study focuses on the optimizat...

In the continuous struggle for improvements in laboratory processes, flow synthesis has been widely used for being safer, more reproducible, as for improving yields and scalability. Therefore, flow ozonolysis has become a turning point as flow reactors provides a much safer work environment and reactions can now be produced at industrial scales. In...

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...

This study investigated the oxidation of 5-hydroxymethylfurfural (HMF) to produce valuable products such as 2,5-furandicarboxaldehyde (DFF), 5-formyl-2-furancarboxylic acid (FFCA) and 2,5-furandicarboxylic acid (FDCA) through (photo) chemical and enzymatic catalysis. Laccases...

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...

In this study, we describe a light-driven photocatalytic decarboxylation of palmitic acid and related fatty acids using Chlorella variabilis fatty acid photodecarboxylase (CvFAP). By utilizing violet LED light (50 W; 397 nm), we achieved a remarkable conversion efficiency of 99% within just 4 minutes, surpassing the previous 79% conversion achieved...

Lignocellulosic biomass can be valorized by fast pyrolysis, generating a bio-oil with levoglucosan (BoE), anhydrous sugar applied as building block for several compounds of great industrial interest. In this work we demonstrated for the first time the direct transesterification of BoE with different acyl donors by free and immobilized lipases. Infl...

Fast, effective and chromatography column-free chemical synthesis of molnupiravir.

l‐Methionine γ‐lyase (MGL) is a PLP‐dependent enzyme which catalyzes the α, γ‐elimination reaction in sulfur containing amino acids, such as L‐methionine and L‐cysteine. Its major applications are on metabolic restriction of methionine to cancer cells, food industry (cheese flavor) and for the synthesis of d and l‐homoalanine. Herein, we present th...

The fatty acid photodecarboxylase from Chlorella variabilis NC64A (CvFAP) promotes the elimination of CO2 from fatty acids (Cn) producing the corresponding hydrocarbon (Cn-1). Therefore, this enzyme is of great biotechnological interest since it can be used in alternative biofuel production routes matching the concept of green chemistry. However, d...

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 ou...

α-Terpineol is a naturally occurring monoterpene present in essential oils, of high value on the market as it is widely used as flavoring in the cosmetics and food industry. This study aims to produce α-terpineol by two different synthetic strategies, using both batch and continuous flow systems, focusing on the optimization of the process, improvi...

Lamivudine (3TC) is a drug in the antiretroviral class used to treat AIDS / HIV. Featuring two chiral centers, 3TC has two pairs of diastereomers, of which cis - (−) is the first option, as it has biological activity and is not cytotoxic. Due to the great demand for this compound, several synthetic routes were developed for its production. Among th...

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...

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

The chemistry behind the discovery of local anesthetics is a beautiful way of understanding the development and improvement of medicinal/organic chemistry protocols towards the synthesis of biologically active molecules. Here in we present a brief history based on the chemistry development of the most used local anesthetics trying to draw a line be...

This work investigates batch and continuous-flow heterogeneous catalytic hydrogenation of a mixture of cafestol and kahweol (C&K) to obtain pure cafestol. These diterpenes were extracted from green coffee beans, and hydrogenation was performed using well-established palladium catalysts (Pd/C, Pd/CaCO3, Pd/BaSO4, and Pd/Al2O3) and a carbon black-sup...

The development of efficient catalytic systems is a fundamental aspect for the straightforward production of chemicals. During the last years, covalent organic frameworks (COFs) emerged as an exciting class of organic nanoporous materials. Due to their pre‐designable structure, they can be prepared with distinct physicochemical characteristics, spe...

Monoacylglycerols (MAGs) are amphiphilic compounds with many applications such as emulsifiers, solubility agents and chiral building blocks. They are currently produced by alkaline glycerolysis under high pressure and temperature, resulting in low yields and by-products formation. Lipase-catalyzed processes are alternative tools that may lead to a...

Recent papers estimates that about 40 % of drugs present chiral amines in their structure and their synthesis in a sustainable and cost-competitive way is still a challenge for the industry. Kinetic resolution is one of the most applied method to produce these desired compounds where the association with lipase as a catalyst is a good alternative....

Benzocaine (ethyl p-aminobenzoate), ethyl ester of p-aminobenzoic acid, is an anesthetic acting as a blocker of the nerve impulses and reducing the permeability of neuronal membrane to sodium iodide, it has become widespread in the pharmaceutical industry having applications as an anesthetic prior to exams such as endoscopy or as a “retarding” agen...

Lignocellulosic biomass is the most abundant carbon source and it is a base of the whole biorefinery concept. Levoglucosan (1,6-anhydro-β-D-glucopyranose) (LG) is an anhydrous sugar formed as major product during pyrolysis of cellulose. LG might be a promising chemical platform. It can be converted to different highly added-value chemicals such as...

α-Terpineol is a monoterpene naturally present in essential oils, of high value on the market as it is a compound widely used as a flavoring, aromatic substance in the cosmetics and food industry. This study aims to produce α-terpineol by two different synthetic strategies, using both batch and continuous flow systems, focusing on the optimization...

Lignocellulose-based bamboo powder was used as pristine support to immobilize two different biocatalysts: Candida Antarctica lipase B and Rhizomucor miehei lipase. Both, IB-CalB and IB-RM, physically absorbed on bamboo carrier presented considerable recycling efficiency, up to 10 consecutive cycles, in batch mode for the ethyl palmitate synthesis w...

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 ef...

Continuous-flow chemistry is an enabling technology which offers great advantages when combined with green chemistry principles toward the development of a more sustainable chemical process. Herein, we present some of the developments made so far on the continuous-flow process that can help researchers to have a different view on how this technolog...

Every year, a large amount of residual agroindustrial waste has been generated and only around 10% is in fact reused. The development of new strategies for biomass valorization is important to add value to these commodities, since biomass is an excellent alternative feedstock to obtain chemicals of interest from renewable resources. The major compo...

Capecitabine is an important anti-cancer drug which synthesis comprises late stage carbamoylation and ester hydrolysis. Here in we report the use of Schotten-Baumann reaction in order to perform these transformation in one single pot, both in batch and continuous flow. Under batch Capecitabine was obtained in 82% yield in 5h while under continuos f...

The combination of chiral supported‐organocatalysts and flow chemistry promotes the sustainable production of enantioenriched compounds providing a very powerful tool for chemical and pharmaceutical industries. However, the rapid deactivation of these catalysts in heterogeneous asymmetric reactions has been limiting the expansion of the area. In th...

Among several value-added products from glycerol, glyceryl carbonate (GC) has gained prominence during the recent years because of its attractive physicochemical properties and the wide range of industrial applications. As a continuation of our efforts on GC production under environmentally benign conditions, in this work, we have applied a combina...

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 lev...

Enantiomerically pure alcohols and amines are important building blocks for the pharmaceutical and agrochemical industries. Among the different approaches to reach these compounds, enzyme-catalyzed kinetic resolution (EKR) of racemates is one of the most widely studied and employed methodologies. In this kind of reaction, the acyl donor plays an im...

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, we describe the combination of the Suzuki‐Miyaura reaction to synthesize biaryl compounds followed by a transaminati...

The decarboxylation of amino acids in presence of a carboxylic anhydride leading to the corresponding ketones, known as Dakin-West reaction, is about to complete almost one century of discovery. In this review, we firstly present the chronological progress in the mechanistic study of the reaction, with an overview about types of substrates, anhydri...

Gliflozins are an important class of prescribed drugs used to treat type II diabetes. They reduce blood sugar levels by targeting the sodium-glucose transport protein 2 (SGTL2) and consequently inhibiting glucose reabsorption in the kidney. There are currently a few FDA-approved gliflozins and others in the pipeline to be launched in the next years...

Cafestol and kahweol (C&K), two coffee diterpene alcohols with structural similarity which exhibit anticarcinogenic effects, were isolated from green coffee Arabica beans, followed by their lipase-catalysed esterification and purification by preparative high-performance liquid chromatography (HPLC). The isolation and enzymatic synthesis parameters...

This chapter shows the developments made so far by researchers worldwide regarding the process development at room temperature using biocatalysts such as hydrolases, transaminases, and laccases. Aminetransaminases (ATAs) have turned out to be interesting enzymes for the asymmetric synthesis of enantiomerically pure amines and in cascade reactions....

Aims: To screen twenty microorganisms for ω-transaminase activity by the kinetic resolution of rac-1-phenylethylamine, followed by testing rac-amines of pharmaceutical interest with bulky substituents and, to conduct the asymmetric synthesis of a chiral amine. Methods and results: Stemphylium lycopersici was selected as the best biocatalyst. By...

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 a...

In this work lipase CaLB was immobilized on functionalized Pd-SiO2 nanoparticles in order to simplify the DKR of α-methylbenzylamine. Hybrid biocatalysts showed immobilization efficiencies of 82%, 80% and 76% when containing 1, 5 and 10% of Pd respectively. On DKR reaction values of ee > 99% and conversion of 82% were found with only 1% of Pd, gene...

The retrosynthetic concepts using enzymes as biocatalysts described for C−N, C−O and C−C bond formations are highlighted. A range of examples for the combination of biocatalysis with chemical reactions is illustrated for the synthesis of drugs and APIs such as Crispine A, Sitagliptin or Atorvastatin. For more details, see the Review by R. O. M. A....

The asymmetric synthesis of serinol-derivatives was investigated employing different amine transaminases as biocatalysts. Under the optimized conditions conversions up to 92% and excellent enantiomeric excesses up to 99% ee were obtained providing access to both, the (R)- and (S)-configurations of the serinol-monoester (2-amino-3-hydroxypropyl hexa...

Herein we report a convenient, fast and high-yielding method for the generation of the racemic amide anaesthetics mepivacaine, ropivacaine and bupivacaine. Coupling of α-picolinic acid and 2,6-xylidine under sealed vessel microwave conditions generates the intermediate amide after a reaction time of only 5 minutes at 150 °C. Subsequent reaction in...

O Crizotinibe é um agente anticancerígeno aprovado para tratamento de carcinoma de pulmão de células grandes. Segundo a análise retrossintética (FRANÇA e col., in press), o 1-(2,6-dicloro-3-fluorofenil) etanol é um intermediário importante, que pode ser produzido por diferentes abordagens biocatalíticas (CUI e col., 2011). Logo, o objetivo foi prep...

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 chira...

Herein, we report a method for the continuous flow DKR of rac-1-phenylethanol catalyzed by CAL-B and VOSO4, using a single packed-bed containing both catalysts. Taking advantage of continuous flow techniques to circumvent compatibility issues, the DKR of rac-1-phenylethanol could be performed continuously to give enantiopure (R)-esters with excelle...

Lead-In: 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 funct...

Enzyme immobilization has achieved important goals during the recent years trying to overcome the drawbacks of free enzyme catalysis. Up to now many strategies can be used in order to immobilize enzymes, some methods can be very simple such as adsorption or more complex as covalent immobilization. This chapter will cover some aspects of enzyme immo...

A catalyst free decarboxylative trichloromethylation of imines to afford different trichloromethyl sulfonyl and sulfinyl amines has been presented. Only DMSO as a solvent at room temperature was necessary to provide the corresponding products in good to high isolated yields. A highly diastereoselective version was carried out, leading to the sulfin...

Two commercially available and widely used enzymes, the parent Thermomyces lanuginosus lipase (TLL) and the shuffled phospholipase A1 LecitaseTM (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 scatte...

In this paper we present prototyping of mesofluidic and microfluidic photocatalytic devices, functionalized through incorporation of TiO2 nanoparticles in polydimethylsiloxane (PDMS), and comparison of their efficiencies for the degradation of rhodamine B (10-5 mol L-1). The prototyping of the photocatalytic devices involves simple and low cost pro...

C-nucleosides are an under explored 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. N2-aryl-1,2,3-triazole C-nucleoside compounds that could be...

Several value-added products can be produced from glycerol and from those glycerol carbonate (GC) has received much attention in recent years because of their physical properties, nontoxicity, water solubility and wide application in chemical, pharmaceutical and food industry. As a continuation of our efforts on producing GC under environmentally a...

The use of continuous-flow chemistry has shown to be an important tool in improving API manufacture. In the present paper, we report the use of continuous-flow reactors in the synthesis of the bicyclic side chain of antiretroviral Darunavir.

Development of asymmetric transformations for the synthesis of chiral molecules has achieved great results in the last decade. Besides the great evolution achieved during recent years in the biotechnology and biocatalysis fields, industrial processes using enzymatic approaches are few and a more broad application of such technology towards the synt...

Microbial lipases have great industrial interest. However, few studies explore the potential of endophytic fungi, micro-organisms that apparently not cause any damage to your host1, as production source of these enzymes. Our research group isolated many endophytic fungi associated with some plant species, which may represent important sources of pr...

Herein we present a high-temperature/high-pressure continuous flow synthesis of 1H-4-substituted imidazoles starting from α-bromoacetophenones and carboxylic acids. 1H-4-aryl imidazoles are key building blocks in the synthesis of NS5A inhibitors, including daclatasvir as the most prominent example. The reaction sequence started with the generation...

In the field of organic chemistry, microwave irradiation proved to be a powerful method to enhance chemical processes. In many instances, the use of sealed-vessel high-temperature microwave processing was able to dramatically reduce reaction times, consume less solvent, increase yields, reduce side reactions and improve reproducibility. Microwaves...

Porphyrin synthesis by classical methods frequently involves the use of high temperatures, toxic and dangerous reagents yielding the product in very low amounts and with poor scalability. Herein, we have studied the synthesis of meso-substituted porphyrins under continuous flow conditions, thus demonstrating scale-up for the porphyrin synthesis in...

This review deals with the important changes that have taken place in the last twenty to thirty years, on the directions and objectives of organic synthesis. Target oriented synthesis now competes with diversity oriented synthesis, and variations, in an attempt to occupy chemical space more completely. At the same time practicality, efficiency, sca...

The present study describes the preparation of N-aryl-(15) and N-alkyl-(17) acetoacetamides, in good to excellent yields, using both conventional and microwave heating, by reaction of amine derivatives (14 and 16) with 2,2,6-trimethyl-4H-1,3-dioxin-4-one (TMD, 12) in aqueous medium. The acetoacetamides were used to prepare novel Biginelli dihydropy...

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-c...

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. CTZ was nanoencapsulated in tween 80 micelles, which generate...

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 ac...

Two novel coordination polymers (CPs) have been synthesized, characterized and successfully applied as robust heterogeneous catalysts for the Biginelli multicomponent reaction to obtain 3,4-dihydropyrimidin-2(1H)-one or thione (DHPMs) derivatives. The reaction was initially developed using both CPs and the Zn-based material showed much better catal...

Sugar-based organogels are important esters for the cosmetic, food and pharmaceutical industries due to their intrinsic properties. Chemical routes to obtain these molecules suffer from low yields and undesirable side products. In this way, biocatalysis can be an interesting and efficient alternative, which meets the green chemistry principles. Her...

The fruits of Pilosocereus arrabidae (Cactaceae) is found in the Grumari shoal, located in the Rio de Janeiro state, Brazil and, several studies have already highlighted the importance of consuming its fruits. This work aims to investigate the physical, mineral and physicochemical properties of its fruits as well as to establish the knowledge about...

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 react...

E.coli cells that contain overexpressed alcohol dehydrogenases (ADHs) were screened as biocatalysts for the stereoselective reduction of chloroketones 5a-d, the corresponding halohydrins 6a-d of which are building blocks in the synthesis of antiretroviral drugs. Among them, ADH from Sphingobium yanoikuyae was found to reduce chloroketone 5c with a...

Packed bed reactors can be used as an interesting alternative on the bioreduction of β-ketoesteres mediated by immobilized microorganisms. Here in, we report our results on the bioreduction of ethyl 3-oxohexanoate by immobilized Kluyveromyces marxianus cells and tert-butyl 3-oxobutanoate by immobilized Rhodotorula rubra cells under continuous flow...

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...

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 regardin...

Flow photochemistry is a growing field and has shown many interesting applications in the recent years due to the versatility of the technique related to the flexibility on the construction of the apparatus needed for the required transformation. The use of available materials and commercial source of light makes it an attractive option to several...

Immobilization of enzymes is important to improve their stability and to facilitate their recyclability, aiming to make biocatalytic processes more efficient. One of the important aspects is the utilization of cheap, abundant, and environmentally friendly carriers for enzyme immobilization. Here we report the use of functionalized cellulose for lip...

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