Ana Alcudia

Enantiopure sulforaphane analogues with various substituents at the sulfinyl sulfur: asymmetric synthesis and biological activities.

A convergent and high-yielding approach for the asymmetric synthesis of sulforaphane 2 and four analogues differently substituted at the sulfinyl sulfur has been developed. The key step of the synthesis is the diastereoselective synthesis of sulfinate ester 23-S(S), using the DAG (diacetone-D-glucofuranose)-methodology. The biological activity of these compounds as inductors of phase II detoxifying enzyme has been studied by determining their ability to activate the cytoprotective transcription factor Nrf2.

Sulfolefin: highly modular mixed S/olefin ligands for enantioselective Rh-catalyzed 1,4-addition.

Reported is a single high yielding step approximation to mixed olefin/sulfinamide ligands enclosing a chiral sulfur atom as the sole chiral center. The synthetic design is validated by a rapid optimization of the substituent at the sulfinyl sulfur, and by the synthesis of an efficient, highly enantioselective catalyst for the Rh-catalyzed 1,4-addition of boronic acids to both, cyclic and acyclic olefins.

Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs

Oxidative therapy is a relatively new anticancer strategy based on the induction of high levels of oxidative stress, achieved by increasing intracellular reactive oxygen species (ROS) and/or by depleting the protective antioxidant machinery of tumor cells. We focused our investigations on the antitumoral potential of amitriptyline in three human tumor cell lines: H460 (lung cancer), HeLa (cervical cancer), and HepG2 (hepatoma); comparing the cytotoxic effect of amitriptyline with three commonly used chemotherapeutic drugs: camptothecin, doxorubicin, and methotrexate. We evaluated apoptosis, ROS production, mitochondrial mass and activity, and antioxidant defenses of tumor cells. Our results show that amitriptyline produces the highest cellular damage, inducing high levels of ROS followed by irreversible serious mitochondrial damage. Interestingly, an unexpected decrease in antioxidant machinery was observed only for amitriptyline. In conclusion, based on the capacity of generating ROS and inhibiting antioxidants in tumor cells, amitriptyline emerges as a promising new drug to be tested for anticancer therapy.

A generalization of the base effect on the diastereoselective synthesis of sulfinic and phosphinic esters

Abstract Various chiral secondary alcohols have been used to study the dependence of the stereochemical outcome of sulfinate and phosphinate ester synthesis on the nature of the base used to catalyse the reaction. From this study it has been shown that the achiral stereodirecting base effect determined in the DAG methodology is a general behaviour in the asymmetric synthesis of sulfinate and phosphinate esters.

Flexible C2-Symmetric Bis-Sulfoxides as Ligands in Enantioselective 1,4-Addition of Boronic Acids to Electron-Deficient Alkenes

The application of acyclic C2-symmetric chelating bis-sulfoxide ligands in the Rh(I)-catalyzed enantioselective 1,4-addition of boronic acids to electron-deficient alkenes is reported. Among the acyclic ethane-bridged bis-sulfoxides tested, the ligand Ferbisox (11), bearing ferrocenyl moieties as substituents at the sulfinyl sulfurs, has exhibited the best results in terms of chemical yield (up to 96%) and enantioselectivity (up to 97% ee). The conjugate addition takes place smoothly in toluene at room temperature in short reaction times (typically 2 h). The reaction scope, including the use of different boronic acids, five-, six-, and seven-membered cyclic enones, an unsaturated lactone, and the most challenging acyclic ketones, is reported. An X-ray diffraction study of the [Ferbisox·RhCl]2 precatalyst clearly exhibits a dimeric structure with an S coordination of the sulfoxide to rhodium. On the basis of the X-ray data and on structural studies conducted in solution by (1)H NMR, a model explaining the high enantioselection observed is proposed.

Unprecedented base effect on the synthesis of chiral phosphinate esters: A new route to P-chiral phosphine oxides of high enantiomeric purity

Abstract The stereochemical outcome of the reaction of chiral secondary alcohols with a phosphinyl chloride was found to be highly dependent on the achiral base used. Thus, the reaction of the readily available sugar derived carbinols, 1 and 2 , with methylphenylphosphinyl chloride in the presence of triethylamine yields stereoselectively the corresponding S np-phosphinates 3 S p and 5 S p in 94 and 92% diastereomeric excess (de). Simply changing the base from triethylamine to pyridine affords R p-phosphinates 4 R p and 6 R p epimers to 3 S p and 5 S p at the phosphinyl phosphorus in 50 and 40% de respectively. These phosphinate esters were found to be good P-chiral transferring intermediates, they react with Grignard reagents under very mild conditions to give the corresponding phosphine oxides. Both enantiomers S p- and R p- o -anisylmethylphenylphosphine oxide (PAMPO) as well S p- and R p- methylphenylpropyl phosphine oxide were obained enantiomerically pure in high yields

Quantitative characterization of desorptive stripping voltammograms complicated by surface dimerization reactions. Application to the reductive desorption of thiols from mercury

Abstract The influence of analyte adsorption and of a follow-up surface dimerization reaction on desorptive stripping voltammograms has been investigated. A modified version of the spline orthogonal collocation technique has been developed to compute the voltammetric response under Langmuirian reversible conditions. Simple analytical expressions derived for surface-confined redox processes are shown to reproduce the stripping voltammograms only in the presence of significant ( θ * R >0.01) analyte adsorption. In the absence of analyte adsorption, asymmetrical waves are obtained as an intrinsic characteristic of the stripping protocol. Empirical equations relating the stripping peak potential and the voltammetric half-height width with scan rate and adsorbed product coverage are presented. Voltammetric scan rate dependence is shown to provide a quantitative estimate of the analyte adsorption extent, whereas its dependence on adsorbed product coverage allows one to identify the presence of surface dimerization processes. Maximum surface excesses and dimerization equilibrium constants can readily be obtained by plotting the reciprocal half-height width versus the surface concentration of stripped species. In the absence of analyte adsorption, a complementary convolutive analysis is also proposed. Application is made to the cathodic stripping of three mercaptocarboxylic acids differing in their hydrocarbon chain-length. The extent of oxidized product dimerization is shown to display a strong dependence on the solution pH, so that higher peak current sensitivities are found in acidic solutions, where oxidized products are present as dimers.

SYNTHESIS OF ENANTIOMERICALLY PURE (R)- AND (S)-2-ETHOXYCARBONYLMETHYL-2-HYDROXY-CYCLOHEXANONES

Abstract Sulfenylation of 2-p-tolylsulfinyl cyclohexanone can be achieved at −78°C with thiosulfonates. The in situ aldol reaction of these compounds with ethyl acetate enolate is highly stereoselective (1,2-asymmetric induction) and yields diastereomeric mixtures of β-hydroxyesters (the configuration of the major one being dependent on the sulfenylating agent) that can be readily separated and transformed into the enantiomerically pure title ketones.

Synthesis and Stereoselective Halogenolysis of Optically Pure Benzylstannanes

In this work we show that lithium ortho-sulfinyl benzylcarbanions are highly efficient reagents for the synthesis of optically pure benzylstannanes by reacting with halotriorganyl tin (up to >98:2 dr). The stereoselectivity of these reactions is opposite to those observed with carbon electrophiles. Bromolysis of the obtained ortho-sulfinylbenzylstannanes with Br(2) in the presence of CuBr takes place in a highly stereoselective way (up to 90:10 dr) with retention of the configuration, which allows the synthesis of optically pure 2-sulfinylated benzyl bromides. Different experiments support the proposed mechanistic rationalization for both processes.