Gabriela Guillena

A highly efficient solvent-free asymmetric direct aldol reaction organocatalyzed by recoverable (S)-binam-L-prolinamides. ESI-MS evidence of the enamine-iminium formation.

Recoverable (S(a))-binam-L-prolinamide in combination with benzoic acid is used as catalysts in the direct aldol reaction between cycloalkyl, alkyl, and alpha-functionalized ketones and aldehydes under solvent-free reaction conditions. Three different methods are assayed: simple conventional magnetic stirring, magnetic stirring after previous dissolution in THF and evaporation, and ball mill technique. These procedures allow one to reduce not only the amount of required ketone to 2 equiv but also the reaction time to give the aldol products with regio-, diastereo-, and enantioselectivities comparable to those in organic or aqueous solvents. Generally anti-isomers are mainly obtained with enantioselectivities up to 97%. The reaction can be carried out under these conditions also using aldehydes as nucleophiles, yielding after in situ reduction of the aldol products the corresponding chiral 1,3-diols with moderate to high enantioselectivities mainly as anti-isomers. The aldol reaction has been studied by the use of positive ESI-MS technique, providing the evidence of the formation of the corresponding enamine-iminium intermediates.

Solvent-free direct enantioselective aldol reaction using polystyrene-supported N-sulfonyl-(Ra)-binam-D-prolinamide as a catalyst

The immobilization of N-sulfonyl-(Ra)-binam-D-prolinamide using polystyrene as a support allows the recovery of an efficient catalytic system for the enantioselective direct aldol reaction between different ketones and aldehydes under solvent-free or aqueous conditions. The polystyrene-supported N-sulfonyl-(Ra)-binam-D-prolinamide catalyst in combination with benzoic acid showed similar results to those obtained with unsupported N-tosyl-binam-derived prolinamide under similar reaction conditions. The aldol products were obtained at room temperature and using only 2 equivalents of the ketone with high yields, regio-, diastereo- and enantioselectivities. The aldol reaction between aldehydes can also be performed under these reaction conditions with moderate results. The recovered catalyst can be reused up to six times without having a detrimental effect on the achieved results.

SPR Studies of Carbohydrate–Protein Interactions: Signal Enhancement of Low-Molecular-Mass Analytes by Organoplatinum(II)-Labeling

The relatively insensitive surface plasmon resonance (SPR) signal detection of low‐molecular‐mass analytes that bind with weak affinity to a protein—for example, carbohydrate–lectin binding—is hampering the use of biosensors in interaction studies. In this investigation, low‐molecular‐mass carbohydrates have been labeled with an organoplatinum(II) complex of the type [PtCl(NCNR)]. The attachment of this complex increased the SPR response tremendously and allowed the detection of binding events between monosaccharides and lectins at very low analyte concentrations. The platinum atom inside the organoplatinum(II) complex was shown to be essential for the SPR‐signal enhancement. The organoplatinum(II) complex did not influence the specificity of the biological interaction, but both the signal enhancement and the different binding character of labeled compounds when compared with unlabeled ones makes the method unsuitable for the direct calculation of biologically relevant kinetic parameters. However, the labeling procedure is expected to be of high relevance for qualitative binding studies and relative affinity ranking of small molecules (not restricted only to carbohydrates) to receptors, a process of immense interest in pharmaceutical research.

Glycine and Alanine Imines as Templates for Asymmetric Synthesis of α‐Amino Acids

The present paper is an overview of new methods for the asymmetric synthesis of different types of α-amino acids. These methods are based on alkylation and condensation reactions of glycine and alanine imine derivatives, which can be carried out under very mild and simple reaction conditions. The enolates generated from these types of reagents are very soft and can be alkylated in a highly diastereoselective manner, even at room temperature, by using chiral templates or asymmetric PTC conditions. These methodologies afford monoalkylated and dialkylated α-amino acids as well as heterocyclic derivatives. In the case of cyclic imine derivatives with oxazinone or pyrazinone structures, the condensation reaction under PTC conditions or with Eschenmoser’s salt allows the preparation of chiral α,β-didehydro-α-amino acid derivatives which can be hydrogenated, cyclopropanated or submitted to Diels−Alder cycloadditions to afford N-methylated and cyclic α-amino acids.

Bio-renewable enantioselective aldol reaction in natural deep eutectic solvents†

Among the deep eutectic solvents (DES), natural deep eutectic solvents (NADES) formed by D-glucose and racemic malic acid are suitable media to perform the enantioselective L-proline catalyzed intermolecular aldol reaction, creating simultaneously and selectively a C–C bond and a new stereocenter. The scope of the reaction was found to be broad, with products being obtained with good levels of diastereo- and enantioselectivities. Furthermore, when the reaction was performed at a large scale, the catalyst together with the reaction media can be recovered by simple water extraction and reused at least three times affording similar results. Therefore, the use of NADES as reaction media to carry out a VOCfree selective process has been demonstrated for the first time. The process is clean, cheap, simple and scalable and meets most of the criteria to be considered as a sustainable and bio-renewable process, with the reaction media and catalyst arising directly from Nature.

Covalently Bonded Platinum(II) Complexes of α-Amino Acids and Peptides as a Potential Tool for Protein Labeling

Arylplatinum(II) complexes have been covalently bonded to the N and C termini and to the alpha-carbon of various amino acid derivatives. These organometallic-functionalized amino acid compounds can be converted into the corresponding free amino acids under both basic and acidic conditions; this demonstrates the excellent stability properties of these biomolecules. Due to the NMR activity displayed by the 195Pt nucleus (natural abundance 33.8%, I = 1/2) these compounds are functional bio-markers. Furthermore, the ability of the arylplatinum functional group to bind SO2 gas, selectively and reversibly as indicated by changes in the spectroscopic properties (1H, 13C, 195Pt NMR and UV spectra) of these compounds, allows for the potential use of these complexes as in vitro biosensors.

Unexpected metal base-dependent inversion of the enantioselectivity in the asymmetric synthesis of α-amino acids using phase-transfer catalysts derived from cinchonidine

Abstract New cinchonidinium salts bearing a 3,5-dialkoxybenzyl group show an alkaline metal base-dependent reversal of enantioselectivity when used as phase-transfer catalysts in the asymmetric alkylation of N -(diphenylmethylene)glycine isopropyl ester with benzyl bromide. The use of potassium hydroxide as base in this alkylation reaction afforded the ( S )-enantiomer, whereas using sodium hydroxide under the same conditions afforded the corresponding ( R )-enantiomer.

The Suzuki cross-coupling reaction: a powerful tool for the attachment of organometallic ‘NCN’-pincer units to biological scaffolds☆

Platinum(II) and palladium(II)NCN {NCN is the terdentate coordinating monoanionic ‘pincer’ ligand [C6H3(CH2NMe2)2-2,6]−} complexes have been covalently bonded via their para-position to both the α-carbon of an α-amino acid and to the γ-position of an alkyl phosphonate by means of Suzuki cross-coupling reactions. The resulting platinum(II) complexes can be used as biomarkers, while the palladium(II) analogs are active Lewis-acid catalysts. Both the pincermetal substituted α-amino acid and phosphonate can be used to introduce these organometallic units in biomolecules such as proteins or enzymes.

Recent Advances on the Organocatalyzed Enantioselective α-heterofunctionalization of Carbonyl Compounds

Spanish Ministerio Ciencia e Innovacion (Consolider Ingenio 2010 CSD2007-00006, CTQ2007-65218/BQU) and the Generalitat Valenciana (Proyecto Prometeo 2009/039).

Palladium(II) pincer complexes of α-amino acids: towards the synthesis of catalytically active artificial peptides

NCN palladium(II) complexes have been covalently attached to the N- and C-termini of l-valine and to the N-terminus of the dipeptide l-Phe-l-Val-OMe. Remarkably, the hydrolysis of the NCN-Pd(II) l-Val-OMe compound afforded the corresponding palladated, free amino acid without affecting the metal site. This deprotected amino acid could be coupled to any protein, enzyme or peptidic chain by simple peptide chemistry. These bioorganometallic systems were active as catalysts in the aldol reaction between methyl isocyanate and benzaldehyde.