Reconfigurable Flow Platform for Automated Reagent Screening and Autonomous Optimization for Bioinspired Lignans Synthesis.

Naturally occurring benzoxanthenones, which belong to the vast family of lignans, are promising biologically relevant targets. They are biosynthetically produced by the oxidative dimerization of 2-propenyl phenols. In this manuscript, we disclose a powerful automated flow-based strategy for identifying and optimizing a cobalt-catalyzed oxidizing system for the bioinspired dimerization of 2-propenyl phenols. We designed a reconfigurable flow reactor associating online monitoring and process control instrumentation. Our machine was first configured as an automated screening platform to evaluate a matrix of 4 catalysts (plus the blank) and 5 oxidants (plus the blank) at two different temperatures, resulting in an array of 50 reactions. The automated screening was conducted on micromole scale at a rate of one fully characterized reaction every 26 min. After having identified the most promising cobalt-catalyzed oxidizing system, the automated screening platform was straightforwardly reconfigured to an autonomous self-optimizing flow reactor by implementation of an optimization algorithm in the closed-loop system. The optimization campaign allowed the determination of very effective experimental conditions in a limited number of experiments, which allowed us to prepare the natural products carpanone and polemannone B as well as synthetic analogues.

An Autonomous Self-Optimizing Flow Reactor for the Synthesis of Natural Product Carpanone.

A modular autonomous flow reactor combining monitoring technologies with a feedback algorithm is presented for the synthesis of the natural product carpanone. The autonomous self-optimizing system, controlled via MATLAB, was designed as a flexible platform enabling an adaptation of the experimental setup to the specificity of the chemical transformation to be optimized. The reaction monitoring uses either online high pressure liquid chromatography (HPLC) or in-line benchtop nuclear magnetic resonance (NMR) spectroscopy. The custom-made optimization algorithm derived from the Nelder-Mead and golden section search methods performs constrained optimizations of black-box functions in a multidimensional search domain, thereby assuming no a priori knowledge of the chemical reactions. This autonomous self-optimizing system allowed fast and efficient optimizations of the chemical steps leading to carpanone. This contribution is the first example of a multistep synthesis where all discrete steps were optimized with an autonomous flow reactor.

Causas de punción lumbar 1992-1993 / Causes of spinal lumbar puncture 1992-1993

El presente trabajo retrospectivo, muestra resultados de un análisis de 381 historias clínicas, de pacientes hospitalizados entre Enero de 1992 a Diciembre de 1993, en los que se habia realizado punción lumbar ante la sospecha clínica de Meningitis o afección del Sistema Nervioso Central, se observo que ante mayor presencia de signos meníngeos o signos de hipertención intracraneal y alteración de la conciencia, mas número de casos de Meningitis se encontraron. Un número importante de alteraciones electrolítos se tuvo en todos los grupos analizados. La edad de los pacientes vario desde neonatos, hasta adolescentes.