Botanochimie : utilisation de matériel végétal comme alternative originale pour la résolution cinétique du 1-phényléthyl acétate

High valuable enantiomerically pure compounds are potential chiral building blocks for the synthesis of pharmaceutically important molecules, agrochemicals, flavours and asymmetric chiral ligands. A novel methodology coined “botanochemistry” investigates the possibility of using directly freshly cut pieces of various vegetables, without any other processing to perform important chemical transformations. The present work aims to optimize the time required for the preparation of the biocatalysts and to screen among fruit and vegetable organs for this purpose. It was observed that most of those biocatalysts contain specific enzymes that hydrolyse exogenous organic substrates. The red beetroot skin has been selected as the most promising biocatalyst to perform the kinetic resolution of (±)-1-phenylethyl acetate with excellent enantiomeric excess. The main advantage of this approach, as compared to the chemical procedures, (metal- and organo-catalysis), is that the final consequences of these transformations are more ecologically friendly, economically promising and also enables the valorization of by-products issued from agriculture and food industries.Les composés organiques énantiomériquement purs constituent une réserve de briques de construction indispensables à la synthèse de molécules chirales plus complexes, à la base de nombreux principes actifs utilisés dans l’industrie. Ces dernières années, les scientifiques ont manifesté un grand intérêt pour la biocatalyse, mettant notamment en œuvre des enzymes purifiées, en tant que catalyseurs performants de réactions chimiques. Dans le cadre de ce projet, une méthodologie encore plus innovante, appelée la botanochimie a été investiguée. Cette approche permet d’utiliser directement des morceaux de végétaux frais, fruits et légumes, sans aucune extraction des enzymes, pour réaliser les mêmes transformations chimiques. Ce projet de recherche avait pour premier objectif d’identifier des biocatalyseurs capables d’hydrolyser de façon énantiosélective le 1-phényléthyl acétate en alcool correspondant. La peau de la betterave rouge (Beta vulgaris L.) a été sélectionnée comme biocatalyseur le plus adéquat pour réaliser cette transformation avec rapidité et d’excellents excès énantiomériques. Le second objectif visait à identifier et caractériser l’activité enzymatique impliquée dans la réaction étudiée. Notre attention s’est portée sur les lipases, déjà largement utilisées dans l’industrie alimentaire et dans la formulation de détergents, ainsi qu’en chimie organique. L’ensemble des résultats de ce projet permet de rendre compte de toutes les potentialités de la botanochimie. Les principaux avantages de cette approche originale, comparée aux approches chimiques classiques, sont des transformations plus respectueuses de l’environnement, prometteuses sur le plan économique et permettant la valorisation de produits secondaires issus de l’agriculture et des industries agro-alimentaires.(AGRO - Sciences agronomiques et ingénierie biologique) -- UCL, 201

Botanochimie - Utilisation de matériel comme alternative originale pour la résolution cinétique du 1-phényléthyl acétate

() -- UCL, 200

Enantioselective hydrolysis of racemic 1-phenylethyl acetate by an enzymatic system from fresh vegetables

High valuable enantiomerically pure compounds are potential chiral building blocks for the synthesis of pharmaceutically important molecules, agrochemicals, flavors and asymmetric chiral ligands. A novel methodology coined “botanochemistry” investigates the possibility of using directly freshly cut pieces of various vegetables, without any other processing to perform important chemical transformations. The present work aims to optimize the time required for the preparation of the biocatalysts and to screen among fruit and vegetable organs for this purpose. It was observed that most of those biocatalysts contain specific enzymes that hydrolyze exogenous organic substrates. The red beetroot skin has been selected as the most promising biocatalyst to perform the kinetic resolution of (±)-1-phenylethyl acetate with excellent enantiomeric excess. The main advantage of this approach, as compared to the chemical procedures (metal- and organo-catalysis), is that the final consequences of these transformations are more ecologically friendly, economically promising and also enables the valorization of by-products issued from agriculture and food industries

Functional dyspepsia: still a serious challenge for medical practitioners and new drug investigators? A Belgian, French, German and Hungarian opinion.

The diagnosis of Functional Dyspepsia is based on the identification of long term specific symptoms and the absence of organic lesions. Many pathophysiological mechanisms are intricate and, at least, partially responsible for the syndrome. Widely accepted technical procedures for the identification of these mechanisms are missing. The final etiopathology is not yet established. The relationship between symptoms and putative mechanisms is unclear. At the moment of the prescription, the physician faces a real therapeutic gap. Moreover, Functional Dyspepsia is an evolving area of study and knowledge has to be updated regularly. As a result, consultations for Functional Dyspepsia are usually very challenging and patients look desperately for medical support. It is likely that this disease is both under-diagnosed and under-treated. Classifying patients into symptomatic subgroups is a promising approach proposed by Rome III. It is assumed that these subgroups are based on different pathophysiological mechanisms, and may allow for more specific therapeutic approaches. However the assessment of the symptomatic profiles of patients is time-consuming. It is also a risky process, because the Rome III subgroups have yet to be validated. There are currently no translations of the definitions in the different European languages. Interviews of the patients are biased by cultural, educational and subjective factors. Identification of suitable subjects for clinical trials is uneasy for the same reasons and can explain several recent Research and Development (R&D) failures. Therefore, there is a need for an updated, step by step approach, a real diagnostic algorithm of the consultation including the use of simple, clear, universal and cross-cultural validated tools, as word-figure questionnaires, designed to establish the symptomatic profiles of the patients

Setting up a common architecture for EPR in primary care: the Belgian experience.

A couple of years ago, the Belgian Federal Ministry of Health decided to back the development of a basic conceptual model for Electronic Patient Record (EPR) in primary care. Using consensus and modeling relational techniques, a working group of experts and experienced practitioners identified 7 key structuring concepts: Health Care Element, Health Approach, Contact, Subcontact, Service, Health Agent, Period. This model could roughly be seen as a restrictive sub-model of the current CEN proposal (prENV 13940) or as a first step to assess this CEN pre-Norm in Belgium. The conceptual model is already used in teaching activities and in a Belgian software labeling process

A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia

Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and C-13 breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation (P = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating (P = 0.001) and overall symptom score (P = 0.022), and at week 3 for bloating (P = 0.008) and heartburn (P = 0.041). 100 mg was also better than placebo for QOL (physical function) (P = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated