Alessandro B. C. Simas

Evaluation of the performance of differently immobilized recombinant lipase B from Candida antarctica preparations for the synthesis of pharmacological derivatives in organic media

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 enzyme (CALB) after immobilization on different supports in different reactions. As supports, we used Accurel 1000, and three core–shell supports (poly(methyl methacrylate) on the core and on the shell – PMMA/PMMA; poly(methyl methacrylate-co-divinylbenzene) on the core and on the shell – PMMA-co-DVB/PMMA-co-DVB; and poly(styrene-co-divinylbenzene) on the core and on the shell – PS-co-DVB/PS-co-DVB). The popular Novozym 435 was also utilized to assess the features of the new biocatalysts. All these supports adsorbed lipases via interfacial activation of the open form of the lipase on the hydrophobic surface of the supports. The studied reactions were esterification of oleic acid and ethanol in a solvent-free medium, resolution of (±)-1,3,5-O-benzyl-myo-inositol via acylation using vinyl acetate in hexane and resolution of (±)-1,2-O-isopropylidene-3,6-di-O-benzyl-myo-inositol via acylation using vinyl acetate (solvent free system). The results varied depending on the employed supports and on the studied reactions, but some general trends may be observed, pointing to better behavior of LIPB compared to CALB. The use of 4 different supports gave more strength to these differences, as it did not depend on a specific difference between a single support/enzyme pair, but it is more general. Thus, LIPB seems to have some advantages compared to the commercial enzyme on all the reactions assayed in this paper. PS-co-DVB/PS-co-DVB-LIPB is in general the most active preparation (even 50% higher activity was observed). Further investigations are in development to determine the structural reasons for these differences.

Stereocontrolled elaboration of quaternary carbon centers involving the asymmetric michael-type alkylation of chiral imines: an efficient enantioselective access to (+)-vincamine

Abstract Michael adduct (S)- 5 b , resulting from the condensation of chiral imine 4 with methyl acrylate, was transformed in two steps into lactone (S)- 8 b . Tryptamine-induced ring-opening of this lactone gave 9, which was finally converted in three steps into the key tricyclic derivative (S)- 11 b , a known precursor of (+)-vincamine 1.

4-Chromenesulphones: synthesis and transformation to isoflavonoid models ☆

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.

Regioselective lithiations of a pterocarpan skeleton: the first synthesis of (±)-4′-dehydroxycabenegrin A-I

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 first synthesis of racemic 4′-dehydroxycabenegrin A-I, 4. Moreover, dialkylation of 3b at the two most reactive sites could be effected through the generation of a dilithiated species. A preliminary result dealing with diethylcarbamate derivative 3c is also shown.

Selectivity Studies Towards the Synthesis of Novel Biaryl Ureas by (Hetero)Nanocatalysis: Size Control and Support Effects

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 particle size and exploit the surface/cavity effects in the Suzuki–Miyaura reaction. Catalyst recovery in this process was pursued as well. Owing to its excellent performance, ceria was explored as a support for these PdNPs. The heterogeneous catalyst was characterized and investigated in the reaction of N‐(4‐iodo‐aryl),N′‐alkyl urea and phenylboronic acid. Our preliminary results revealed a high activity of the catalyst at 0.5 mol % Pd0 during three consecutive cycles. It is suggested that the specific interface between Pd0 and the high‐surface‐area ceria has a role in the catalytic performance.

Efficient desymmetrization of 4,6-di-O-benzyl-myo-inositol by Lipozyme TL-IM

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 investigation of the effects of solvent, biocatalyst load, and temperature, a more economical procedure resulted. The feasibility of biocatalyst reuse was also shown.

Palladium on Layered Double Hydroxide: A Heterogeneous System for the Enol Phosphate Carbon-Oxygen Bond Activation in Aqueous Media

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-bromoaniline as precursor allowed the synthesis of the 2-phenyl indole through an arylation/Heck cyclization. Catalyst reusability enabled the synthesis of the heterocycle in moderate yields for four consecutive runs.

Hydrophilic cyclodextrin protected Pd nanoclusters: insights into their size control and host–guest behavior

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 palladium coordination sphere. This process is followed by reduction of Pd(II) species according to the α-HPCD concentration. The hydrodynamic radii observed from both PdNPs and α-HPCD aqueous solutions suggested that regular CDs assemblies in the order of a few nanometers may direct the homogeneous NPs growth towards uniform aggregates. These scattering measurements are corroborated by 1H DOSY NMR spectroscopy in solution and AFM (atomic force microscopy) analyses which provided evidence of stable hybrid assemblies. Interestingly, by changing the cavity size, structures with distinct hydrodynamic diameters are formed. Further evidence from ECD (electronic circular dichroism) spectra reveals that the primary face of cyclodextrin is most likely associated to the metal surface.

An expeditious and consistent procedure for tetrahydrofuran (THF) drying and deoxygenation by the still apparatus

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 on the chemical knowledge underlying such procedures. Safety and economy issues concerned with the operation of the THF still apparatus are also discussed.

STRAIGHTFORWARD, ECONOMICAL PROCEDURES FOR MICROSCALE ELLMAN’S TEST FOR CHOLINESTERASE INHIBITION AND REACTIVATION

Samir F. de A. Cavalcantea,b,#, Daniel A. S. Kitagawaa, Rafael B. Rodriguesa, Monique Cardozoa, Reuel L. de Paulaa, Ana Beatriz de A. Correaa and Alessandro B. C. Simasb,* Instituto de Defesa Química, Biológica, Radiológica e Nuclear, Exército Brasileiro, Avenida das Américas 28705, 23020-470 Rio de Janeiro – RJ, Brasil Instituto de Pesquisas de Produtos Naturais Walter Mors (IPPN), Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro – RJ, Brasil