Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease

A substitute for the CO ligand in the form of an electron-poor, chiral phosphorus ligand can be used to synthesize efficient transition-metal catalysts for asymmetric Diels - Alder reactions. In the presence of 2, for example, a-bromoacrolein reacts with cyclohexadiene to form 1 in > 99% ee.Ein geeigneter CO--Ersatz sind elektronenarme, chirale Phosphanliganden, um zu effizienten Übergangsmetallkatalysatoren für die asymmetrische Diels-Alder-Reaktion zu gelangen. Dies belegt beispielsweise die Bildung von 1 mit > 99% ee aus Bromacrolein und Cyclohexadien in Gegenwart von 2

Abstract

A one pot nucleophile/electrophile additiodhydrogenation sequence was applied to [(benzene)Cr(CO)j] to give predominantly the 4,5-trans-disubstituted cyclohexene. Several asymmemc modifications of the sequential addition of C-nucleophiles and C-elecuophiles to (arene)Cr(CO), complexes are discussed. A mechanistically intriguing route involves the use of chiral phosphorous ligands to control the diastereoselectivity in the migratory CO insertion step and/or the reductive elimination step in the sequence. Ephedrine and norephedrine derived ligands gave product ee of up to 69 9%. New C2-chiral bidentate ligands (L*) which emulate some of the bonding characteristics of CO were synthesized and briefly considered for this application. The main interest in these ligands concerns their potential in catalytic C-C bond forming reactions; a first application to the Lewis acid [CpFeL*]+ catalyzed Diels-Alder reaction between enals and dienes was successfully realized.The readily accessible, air stable (arene)Cr(CO)g complexes 1. react with carbanions by addition to the arene exo-face to afford anionic 'q5-cyclohexadienyl complexes 2. In sifu reaction with the appropriate electrophile gives access to aromatic and alicyclic products as shown in Scheme 1 (1-5). Scheme 1. Products resulting from the sequential addition of a C-nucleophile and an electrophile to an (arene)Cr(C0)3 complex. 97

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