Sección de Química Terapéutica

Unidad de Química Farmacéutica

Escolano Mirón, Carmen

Design of new organocascade reactions to access biologically interesting compounds.

The preparation of enantiomerically pure compounds is a continuous social demand due to the clinical advantages that enantiopure drugs offer over the racemic forms. These advantages forced pharmaceutical companies and health authorities to place stereochemically pure substances in a privileged position. Consequently, it is not strange that 7 out of the top 10 most selling-drugs worldwide in 2010 are commercialized as enantiopure forms. The large demand of enantiopure products has broken out the progress of the asymmetric synthesis, considered in the last years as one of the most important areas of research in both industry and academia.

 

One of the key features of the biosynthetic routes in Nature, our source of inspiration, is the achievement of cascade reactions that convert efficiently simple molecules into complex molecular systems. Environmental and health regulations gave strong support to cleaner and non-toxic chemical processes avoiding the use of toxic reagents. Chemical companies concerned about economic and ecological profitability are really interested in cascade reactions. In this sense, the efforts made for the scientific community have driven to the configuration of a new area within the enantioselective synthesis: the organocatalysis defined as the acceleration of chemical reactions by small organic molecules.

Organocascade reactions involve the formation of several chemical bonds and often generate stereogenic centers with excellent stereoselectivity. Such one-pot reactions avoid time-consuming and costly step-by-step processes and are environmentally friendly, and chemical waste is reduced since the intermediates are not isolated and purified. 

The structural diversity present in the biosynthetic molecules is due to the combination of catalytic cascades that involve different enzymes, which activate different substrates. For the success of this catalytic combination, it is essential the capability of different enzymes to coexist in the same media without undesirable interactions. Moreover, some reactions need the participation of coenzymes and metallic cofactors as further substrate activators. For this reason, the efficient combination of organocatalysts with other catalysts, which are able to activate different functional groups, is highly desirable to increase the molecular diversity of the synthetic products. Cooperative catalysis between organic and metal catalysts has evolved rapidly in recent years and its improvement offer to the synthesis of enantiomerically pure compounds levels of reactivity, selectivity and diversity that are very difficult to get using other methodology. Remarkably, this innovative strategy not only promotes single reactions but also enables multiple transformations in a one-pot process for the generation of previously unattainable compounds.

Our research group is interested in the continuing challenge at the forefront of synthetic chemistry of the design and development of new catalytic strategies involving organocascade reactions and cooperative multicatalytic synthetic sequences to access to biologically interesting compounds. 

Organobifunctional and metal cooperative catalysis strategy

 

 

 PUBLICATIONS 2011:

 Amat, M.; Arróniz, C.; Molins, E.; Escolano, C.; Bosch, J. Highly stereoselective double (R)-phenylglycinol-induced cyclocondensation reactions of symmetric aryl bis(oxoacids), Org. Biomol. Chem. 2011, 9, 2175-2184.

 Arróniz, C.; Escolano, C.; Luque, F. J.; Bosch, J.; Amat, M. First asymmetric cascade reaction catalysed by chiral primary amino alcohols, Org. Biomol. Chem. 2011, 9, 5079-5085.

 Arróniz, C.; Gil-González, A.; Semak, V.; Escolano, C.; Bosch, J.; Amat, M. Cooperative catalysis for the first asymmetric formal [3+2] cycloaddition reaction of isocyanoacetates to α,β-unsaturated ketones, Eur. J. Org. Chem. 2011, 3755-3760.

GROUP MEMBERS:

Postdoc: Carlos Arróniz

PhD student: Vladislav Semak

Undergraduate studens: Sonia Abàs

                                   Laura Comellas

                                   Javier Nieto

 Contact details: cescolano@ub.edu

                       Department of Pharmacology and Medicinal Chemistry

                       Laboratory of Organic Chemistry (tel Int. code +93 4024540)

                       Faculty of Pharmacy. University of Barcelona