Alessandro B. C. Simas

• Ph.D.
• Professor at Federal University of Rio de Janeiro

We report herein continuous flow conditions for the TL‐IM lipase‐catalyzed enantioselective desymmetrization of 4,6‐di‐O‐benzyl‐myo‐inositol, a relevant precursor of bioactive myo‐inositol derivatives to the D‐1‐O‐acetyl derivative. This study represents the first example of enantioselective desymmetrization of an inositol under continuous flow con...

In the field of Chemical Defense toward Nerve Agents, the development of analytical methodologies for analysis of different sample matrices, training of human resources in handling, detection of such toxic chemicals, and design of more effective medical countermeasures may be hampered by the lack of infrastructure and well-prepared human resources....

The Wnt/β-catenin signaling pathway dictates cell proliferation and differentiation during embryonic development and tissue homeostasis. Its deregulation is associated with many pathological conditions, including neurodegenerative disease, frequently downregulated. The lack of efficient treatment for these diseases, including Alzheimer’s disease (A...

A presente invenção dispõe sobre a preparação biocatalítica enantiosseletiva de 1,2-dióis quirais e a transformação prática em seus derivados carbonatados e esterificados. Especificamente, refere-se a um novo processo de preparação de álcoois opticamente ativos e seus derivados com alta pureza óptica a partir de precursores racêmicos através de rea...

A recombinant lipase from Candida antarctica, LIPB, was obtained through fermentation using an alternative low-cost medium and immobilized on the distinct mesoporous silica particles. The performance and versatility of the new biocatalysts was evaluated, for the first time, on two biotechnological interest reactions: resolution of racemic myo-inosi...

Organophosphorus poisoning caused by some pesticides and nerve agents is a life-threating condition that must be swiftly addressed to avoid casualties. Despite the availability of medical countermeasures, the clinically available compounds lack a broad spectrum, are not effective towards all organophosphorus toxins, and have poor pharmacokinetics p...

Derivados de vanilinas, seus análogos e derivados, e utilização dos mesmos e seus intermediários como ativadores, reativadores, inibidores ou protetores da acetilcolinesterase inibida por organofosforados e carbamatos, tais como antídotos, paliativos e/ou profiláticos. A presente invenção, ainda, dispõe sobre as estruturas moleculares destes compos...

This article describes acetylcholinesterase (AChE), an enzyme involved in parasympathetic neurotransmission, its activity, and how its inhibition can be pharmacologically useful for treating dementia, caused by Alzheimer’s disease, or as a warfare method due to the action of nerve agents. The chemical concepts related to the irreversible inhibition...

Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share the toxic profile with nerve agents. Pyridinium oximes are the only clinically available antidotes against poisoning by these substances, but their poor...

The use of nerve agents, toxic organophosphorus compounds listed in Chemical Weapons Convention as Schedule 1 chemicals, as warfare has recently drawn much attention from the governments and societies in general. The rush for the structure determination of the elusive Novichok agents, after this class of compounds were allegedly employed in recent...

Casualties caused by nerve agents, potent acetylcholinesterase inhibitors, have attracted attention from media recently. Poisoning with these chemicals may be fatal if not correctly addressed. Therefore, research on novel antidotes is clearly warranted. Pyridinium oximes are the only clinically available compounds, but poor penetration into the blo...

The use of nerve agents, organophosphorus compounds which irreversibly inhibit acetylcholinesterase, in conflicts and terrorism has gained renewed geopolitical status in recent years. As no “universal antidote” has ever been produced, the development of antidotes to reactivate enzyme is clearly warranted. Given the fact that nerve agents are restri...

A presente invenção refere-se a derivados da indolin-2-ona tais como ativadores, reativadores, inibidores ou protetores da acetilcolinesterase inibida por organofosforados e carbamatos, e seus intermediários, relacionados ao campo tecnológico de aplicações terapêuticas e composições farmacêuticas como antídotos, paliativos e/ou profiláticos. Ademai...

The present work aimed to compare the small, neutral and monoaromatic oxime, isatin-3-oxime (isatin-O), to the commercial ones, pralidoxime (2-PAM) and obidoxime, in a search for a new potential reactivator for acetylcholinesterase (AChE) inhibited by the pesticide paraoxon (AChE/POX) as well as a novel potential scaffold for further synthetic modi...

Straightforward, microscale, Ellman’s cholinesterase test procedures are presented, useful for screening of novel compounds aiming at neurodegenerative diseases and antidotes towards nerve agents and pesticides. Herein, we detail the different procedure features and set forth guidelines on experimental choices researchers may make. The detailed p...

This paper deals with challenges that Brazilian Army Organic Synthesis Laboratory has been going through to access reference compounds related to the Chemical Weapons Convention in order to support verification analysis and for research of novel antidotes. Some synthetic procedures to produce the chemicals, as well as Quality Assurance issues and a...

Chiral myo-inositol derivatives play key roles in cell-signaling processes. Despite the relevance of these compounds, few syntheses of them rely on enantioselective catalytic reactions. Even fewer reports describe the use of desymmetrization of myo-inositol derivatives. In fact, most routes involve resolution by derivatization. Thus, a symmetrical...

Nerve Agents are toxic organophosphorus compounds which inhibit cholinesterases, pivotal enzyme in Parasympathetic Neurotransmission. As they are Schedule 1 compounds in accordance to Chemical Weapons Convention, strict controls are applied and some research groups may have their work hampered due to requirements for synthesis and manipulation. Ner...

In this work, a new catalytic approach for the C-O activation of enol phosphates based on a palladium supported on layered double hydroxide was developed. In this case, two different ketene aminal phosphates were used as models to study the synthesis of α -phenyl enecarbamates N-Boc/CBz under the Suzuki-Miyaura conditions. The use of an ortho-bromo...

White biotechnology is the use of enzymes and microorganisms in industrial production through applied biocatalysis. This allows for milder reaction conditions (pH and temperature) and the use of more environmentally-compatible catalysts and solvents. This, in turn, leads to processes which are shorter, generate less waste, making them both environm...

A series of novel biaryl ureas containing different structural patterns have been prepared in good yields in the presence of palladium nanoparticles (PdNPs) with narrow particle size distribution. In particular, α, β-, and γ-hydroxypropylated cyclodextrins were used as reductants/stabilizers under different Pd-to-cyclodextrin ratios to tune the par...

This paper shows the production of lipase B from Candida antarctica (LIPB) after cloning the gene that encoded it in Pichia pastoris using PGK as a constitutive promoter. The production of the lipase is lower using this strategy but it avoids the use of inducers like methanol. The performance of this enzyme was compared with that of the commercial...

Core–shell supports have been prepared and utilized to immobilize lipase B from Candida antarctica. The hydrophobic nature of the supports permitted to immobilize the enzyme via interfacial activation at low ionic strength. Different supports were prepared having different hydrophobicity and crosslinking degree, and compared to the commercially ava...

The enantioselective enzymatic desymmetrization of 4,6-di-O-benzyl-myo-inositol, a myo-inositol derivative, was effectively catalyzed by Thermomyces lanuginosus lipase (TL-IM). The product 1D-1-O-acetyl-4,6-di-O-benzyl-myo-inositol, a useful precursor to inositol phosphates, was obtained in excellent yield and enantiomeric excess. Through the inves...

Sterically hindered myo-inositol derivatives were assayed against different commercial lipases. It was found that DL-1,3,6-tri-O-benzyl-myo-inositol undergoes efficient kinetic resolutions mediated by Pseudomonas sp. lipases (PS-C, PS-IM) and CaLB (Novozym 435). Under the best conditions, the O-acylated Lenantiomorph was obtained in up to >99% ee w...

In this work, we have investigated the biocatalytic continuous flow process with a packed-bed reactor for the kinetic resolution of (+/-)-1,3,6-tri-O-benzyl-rnyo-inositol ((+/-)-1) by alcoholysis using Novozym 435. Excellent conversions and stereselectivities were attained in short reaction time. We found that this enzymatic transformation under co...

We report a straightforward and efficient reaction protocol for the syntheses of substituted ureas via treatment of thioureas with aqueous potassium dichloroiodate (KICl2). By tuning the reaction condition, thioureas bearing activated N-aryl substituents may undergo either selective oxidation or sequential oxidation and iodination, forming iodoaryl...

BACKGROUND: The response surface methodology was successfully applied to the optimization of the reaction variables for the kinetic resolution of a precursor of high-value myo-inositols, ( ± )-1,2-O-isopropylidene-3,6-di-O-benzyl-myo-inositol (( ± )-1), by Novozym 435. The resolutions were run separately, with two acylating agents, ethyl acetate an...

Maternal Wnt/β-Catenin signaling is essential to establish dorsal-specific gene expression required for axial patterning in Xenopus. Deregulation of this pathway causes axis phenotypes in frog embryos. In adult life, mutations in the Wnt pathway components are associated with many diseases, such as polyposis coli; osteoporosis-pseudoglioma syndrome...

myo-Inositol derivatives bearing selectively protected hydroxyl groups are relevant precursors of high-value myoinositols. In the present study, we applied the response surface method to the optimization of kinetic resolution of (±)-1,3,6-tri-O-benzyl-myo-inositol by Novozym 435 (immobilized lipase B from Candida antarctica) with vinyl acetate in h...

The process of formation of narrow size spherical PdNPs covered by cyclodextrins with an average size of 5.1 nm ± 0.5 nm has been investigated in aqueous solution at room-temperature. Analyses by UV-Vis spectroscopy and dynamic light scattering (DLS) at the beginning of reaction indicated a fast exchange of chloride ions with water molecules within...

The study on kinetic resolution of two myo-inositol derivatives by lipases is reported. Treatment of the triether derivative, (±)-1,2-O-isopropylidene-3,5,6-tri-O-benzyl-myo-inositol, with acylating agents in the presence of different lipases did not afford any detectable amount of acylated products. We speculate that the severe steric hindrance po...

Journal of Molecular Catalysis B: Enzymatic j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / m o l c a t b Kinetic resolution of (R,S)-1,2-isopropylidene glycerol (solketal) ester derivatives by lipases a b s t r a c t A study on the enantioselective hydrolysis of (R,S)-1,2-isopropylidene glycerol (4-hydroxymethyl-2,2...

A study on the enantioselective hydrolysis of (R,S)-1,2-isopropylidene glycerol (4-hydroxymethyl-2,2-dimethyl-1,3-dioxolane, solketal) octanoate catalyzed by different lipases was carried out. Among them, Pseudomonas sp. lipase proved to be the most effective. It was shown that the ester bearing the longer octanoyl acyl chain is a more suitable sub...

Transition-metal-catalyzed coupling of amines with aryl halides (or pseudo-halides) has evolved as the most versatile method available to forge carbon-nitrogen bonds. However, due to economic and environmental concerns, the quest for more attractive protocols in both academic and industrial domains has been pursued. In this review, we have summariz...

For Abstract see ChemInform Abstract in Full Text.

(±)-1,2-O-Isopropylidene-3,6-di-O-benzyl-myo-inositol is a relevant starting material in the synthesis of inositol phosphates and their analogs. In this study, we disclose our efforts toward an efficient methodology for the kinetic resolution of this compound by lipase B of Candida antarctica (Novozym 435). This reaction selectively affords L-(−)-1...

Michael adduct , resulting from the condensation of chiral imine 4 with methyl acrylate, was transformed in two steps into lactone . Tryptamine-induced ring-opening of this lactone gave 9, which was finally converted in three steps into the key tricyclic derivative , a known precursor of (+)-vincamine 1.

Optimized reaction conditions afford biaryl compounds (III) in high yields.

Resorcinol derivatives 3-benzyloxy-1-methoxymethoxybenzene (3b) and 4- benzyloxy-1-bromo-2-methoxymethoxybenzene (3c) were regioselectively lithiated. The resulting aryllithium intermediates or their cuprate derivatives were reacted with allyl bromide (4a), prenyl bromide (4b) and (E)-4-benzyl-1-bromo-3-methylbut-2-ene (4c), leading to C-2 and C-4...

Cyclodextrins provide unique opportunities to catalytic applications. The integration of these supramolecular structures and heterogeneous catalysis exhibits potential to fulfill the high demands to the development of sustainable chemical processes. Herein, we have summarized some properties of this important class of catalysts. Selected synthetic...

In this work, we present ligand-free Suzuki cross-coupling reactions in PEG 300 under thermal conditions at 55°C with good yields of conversion; better results were obtained with low reaction time. In 1 hour, 1-iodo-4-nitrobenzene and phenylboronic acid reached 98% of the yield and 9700 of TON. Better results were obtained with Pd(0) sources. The r...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The synthesis of a stable ketene aminal phosphate (α-phosphoryloxy enecarbamate) derived from N,N-diprotected acetamide, bearing two different removable protecting groups, is disclosed. This synthetic intermediate underwent successful palladium-catalyzed cross-coupling reactions to afford functionalized enynes and dienes.

A new approach for the preparation of palladium nanoparticles in water from a renewable source, 2-hydroxypropyl-alpha-cyclodextrin (alpha-HPCD), which acts both as a reductant and capping agent, is presented. The palladium nanoparticles were characterized by using dynamic light scattering (DLS), transmission electron microscopy (TEM) and X-ray phot...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A direct selective protection (O-benzylation) of two or more hydroxyl groups in polyols displaying diverse structural patterns was made possible by the establishment of conditions that enable an efficient turnover for the Bu2Sn group, initially at the corresponding stannylene acetals (only ∼1.0molequiv of Bu2SnO was employed). It was also demonstra...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Despite the availability of alternative methods for drying tetrahydrofuran (THF), the use of the still apparatus, wherein a THF solution containing Na-bezophenone ketyl is heated to reflux, remains widespread. We herein propose a set of procedures to solve the problems usually faced in applying this drying technique. Moreover, a discussion is made...

Cross-couplings of 2-tributylstannyl-N-Boc-2,3-dehydropiperidine, a six-membered cyclic enecarbamate, with aryl iodides and triflates are reported for the first time. Under the Pd(0)/AsPh3 catalytic system (Farina's conditions), better conversions of this challenging substrate into the expected products were achieved with shorter reactions carried...

Enhancing atom economy of the metal-catalyzed asymmetric allylic alkylation (AAA) shifts from the usual nucleophilic displacement of a leaving group to an addition of a pronucleophile to a double bond. Using 1-alkoxyallenes as proelectrophiles, the palladium-catalyzed AAA proceeds with 1,3-dicarbonyl compounds as pronucleophiles with excellent regi...

Edunol (3), a pterocarpan isolated from Harpalyce brasiliana, a plant used in the northeast of Brazil against snakebites, was obtained by synthesis and showed antimyotoxic, antiproteolytic and PLA2 inhibitor properties. These proprieties could be improved through the synthesis of a bioisoster (5), where the prenyl group was replaced by the benzyl g...

A more consistent, straightforward, and economical protocol for generation of stannylene species and their reaction with BnBr leading to products of O-monobenzylation of diols has been set. It has shown to be specially indicated for substrates bearing vicinal trans 1,2-diol moieties on cyclohexane backbones, which are more resistant to these transf...

Novel sulphones derived from chromenes through substitution at C-4 were prepared. It has been shown that, after conjugate addition of phenyl lithium and sulphone function manipulation on the adducts, these molecules lead to isoflavan, isoflavene and isoflavanone models.

Maackiain O-MOM derivative 3b was regioselectively lithiated at the C-10 position of D-ring and reacted with electrophiles. Regioselective lithiation of the C-10 TMS-substituted derivative 5d, followed by organocopper formation and treatment with prenyl bromide, enabled the desired prenylation at C-4. The obtained compound 6d was employed in the fi...

A formal synthesis of (+)-vincamine (1) from (S)-(+)-2-ethyl-2-(2-methoxycarbonylethyl) cyclopentanone (6a) is described. This intermediate had previously been obtained by our research group in 90% ee through d'Angelo's deracemizing alkylation of the chiral imine 7, easily prepared from (R)-(+)-α-methylbenzylamine and 2-ethyl cyclopentanone with me...

Heterocycle-substituted silyl groups have been shown to undergo the requisite protodesilylation reaction under much milder conditions than those employed for the phenyldimethylsilyl substituent. We now report the preparation of 5-methyl-2-furyldimethylsilyllithium which represents an additional means for incorporating such heterocylic silyl groups.

Coupling of 7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran (4a) with 2-chloromercurio-4,5-methylenedioxyphenol (5) yields (±)-6a,12a-cis-dihydro-3-methoxy-4-(3-methyl-2-butenyl)-6H-[1,3]diox olo[5,6]benzofuro[3,2-c][1]benzopyran (6; ±-4-prenylpterocarpin) in an efficient manner. An improved procedure for the preparation of chromenes is reported.