Enantioselective Synthesis of Succinimides by Michael Addition of Aldehydes to Maleimides Organocatalyzed by Chiral Primary Amine-Guanidines

The monoguanylation of (1S,2S)- and (1R,2R)-cyclohexane-1,2-diamine affords chiral primary amine-guanidines that are used as chiral organocatalysts in the enantioselective Michael addition of aldehydes, particularly α,α-disubstituted aldehydes, to maleimides. The reaction is carried out in the presence of imidazole, as an additive, in aqueous N,N-dimethylformamide, as the solvent, and affords the corresponding enantioenriched succinimides in high or quantitative yields with enantioselectivities up to 96 % ee. Theoretical calculations (DFT and M06–2X) suggest a different hydrogen-bonding coordination pattern between the maleimide (C=O) and the catalyst (NH groups) is responsible for the enantioinduction switch that is observed when the reaction is carried out using primary amine-guanidines versus primary amine-thioureas as the organocatalysts.The authors thank the Spanish Ministerio de Economía y Competitividad (MEC) (projects CTQ2010-20387, CTQ2010-21263-C02, and Consolider Ingenio 2010, CSD2007-00006), the Fondos Europeos para el Desarrollo Regional (FEDER), the COST Action CM0905 “Organocatalysis”, the Generalitat Valenciana (Prometeo/2009/039), the Basque Government (GV grant IT-291-07), the University of Alicante, and the University of the Basque Country for the financial support

Enantioselective Michael addition of isobutyraldehyde to nitroalkenes organocatalyzed by chiral primary amine-guanidines

Primary amine-guanidines derived from trans-cyclohexane-1,2-diamines are used as organocatalysts for the enantioselective conjugate addition of isobutyraldehyde to arylated and heteroarylated nitroalkenes. The reaction was performed in the presence of imidazole as the additive in aqueous DMF as the solvent at 0 °C. The corresponding Michael adducts bearing a new stereocenter were obtained in high yields and with enantioselectivities of up to 80%. Theoretical calculations are used to justify the observed sense of the stereoinduction.Spanish Ministerio de Economía y Competitividad (projects CTQ2010-20387, CTQ2010-21263-C02 and Consolider Ingenio 2010, CSD2007-00006), FEDER, the COST Action CM0905 ‘Organocatalysis’, the Generalitat Valenciana (Prometeo/2009/039), the Basque Government (GV Grant IT-291-07), the FP7 Marie Curie Actions of the European Commission via the ITN ECHONET Network (MCITN-2012-316379) and the universities of Alicante and the Basque Country

Staging Parkinson’s Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life

Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL: 1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Results: Four hundred and thirty-nine PD patients (62.05 +/- 7.84 years old; 59% males) were included. MNCD stage was: stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advanced MNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p < 0.0001) and EUROHIS-QOL8 (p < 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD

Staging Parkinson’s Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life

© 2023 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0).Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD).Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity.Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8).Results: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages.Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.COPPADIS and the present study were developed with the help of Fundación Española de Ayuda a la Investigación en Enfermedades Neurodegenerativas y/o de Origen Genético (https://fundaciondegen.org/) and Alpha Bioresearch (www.alphabioresearch.com). Also, we received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017-2020 por el Proyecto “PROGRESION NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”) to develop a part of the COPPADIS project.Peer reviewe

Aminoguanidinas y 1,2-diaminas quirales como organocatalizadores en síntesis enantioselectivas

En el Capítulo I se describe la obtención de nuevas aminoguanidinas a partir de trans-ciclohexano-1,2-diaminas enantiopuras y su empleo como organocatalizadores quirates en la reacción de adición Michael enantioselectiva de aldehídos a maleimidas, para sintetizar succinimidas enantioméricamente enriquecidas, las cuales son estructuras con propiedades biológicas y precursores de otros compuestos de interés como las y-lactamas. Se confirmó experimentalmente la configuración absoluta de los aductos mediante análisis de rayos X de uno de los productos, tras su oxidación, y se llevaron a cabo cálculos DFT para justificar la enantioselección observada en el proceso. Como muestra de la utilidad sintética de las succinimidas quirales obtenidas, se llevó a cabo un proceso one-pot consistente en la secuencia de adición Michael enantioselectiva de aldehídos a maleimidas, aminación reductora del aducto y lactamización final para obtener y-lactamas. Asimismo, estos organocatalizadores fueron empleados en la reacción de adición Michael enantioselectiva de isobutiraldehído a nitroalquenos para sintetizar -y-nitroaldehídos enantioenriquecidos. Asimismo, se realizaron cálculos teóricos para justificar el mecanismo a través del cual evolucionaba este proceso enantioselectivo. En el capítulo II se muestra el uso de 1,2-diaminas quirales comercialmente asequibles como organocatalizadores en la adición conjugada enantioselectiva de aldehídos a maleimidas para sintetizar derivados de succinimidas quirales. Asimismo, se llevaron a cabo cálculos teóricos para justificar la enantioselectividad observada

Enantioselective Michael addition of aldehydes to maleimides organocatalysed by chiral 1,2-diamines: an experimental and theoretical study

Simple and commercially available chiral 1,2-diamines were used as organocatalysts for the enantioselective conjugate addition of aldehydes, including α,α-disubstituted, to maleimides. The reaction was carried out in the presence of hexanedioic acid as an additive in aqueous solvents at room temperature. By employing (1S,2S)- and (1R,2R)-cyclohexane-1,2-diamine as organocatalysts, the corresponding Michael adducts bearing new stereocenters were obtained in high or quantitative yields with enantioselectivities of up to 92%, whereas the use of (1S,2S)-1,2-diphenylethane-1,2-diamine gave a much lower ee. Theoretical calculations were used to justify the observed sense of the stereoinduction.We thank the financial support from the Spanish Ministerio de Economía y Competitividad (projects CTQ2010-20387, CTQ2010-21263-C02 and Consolider Ingenio 2010, CSD2007-00006), FEDER, the COST Action CM0905 ‘Organocatalysis’, the Generalitat Valenciana (Prometeo/2009/039), the Basque Government (GV Grant IT-291-07) and the Universities of Alicante and the Basque Country

Ús de dispositius quotidians per a la determinació de la velocitat del so en l’aire

L’aprenentatge dels conceptes físics per part de l’alumnat es pot assolir d’una manera més significativa si les classes teòriques s’acompanyen d’experiències que permeten il·lustrar-lo de forma pràctica. En aquest treball, s’hi proposa un experiment per a mesurar la velocitat del so en l’aire, on s’utilitza el concepte d’ones estacionàries en un tub semitancat. Consisteix en la generació i l’emissió d’ones sonores d’una determinada freqüència a la part oberta del tub, mitjançant un telèfon mòbil, i mesurar la intensitat del so de l’ona sonora reflectida amb un altre telèfon mòbil. El senyal acústic, en rebotar al fons del tub, produeix una ona estacionària només per a determinades llargàries del tub. En aquesta situació hi ha una relació entre la freqüència de ressonància de l’ona sonora incident, la longitud del tub i la velocitat de propagació del so en l’aire. I si determinem experimentalment la longitud del tub i la freqüència de ressonància és possible obtenir la velocitat del so en l’aire

Ús de dispositius quotidians per a la determinació de la velocitat del so en l’aire

L’aprenentatge dels conceptes físics per part de l’alumnat es pot assolir d’una manera més significativa si les classes teòriques s’acompanyen d’experiències que permeten il·lustrar-lo de forma pràctica. En aquest treball, s’hi proposa un experiment per a mesurar la velocitat del so en l’aire, on s’utilitza el concepte d’ones estacionàries en un tub semitancat. Consisteix en la generació i l’emissió d’ones sonores d’una determinada freqüència a la part oberta del tub, mitjançant un telèfon mòbil, i mesurar la intensitat del so de l’ona sonora reflectida amb un altre telèfon mòbil. El senyal acústic, en rebotar al fons del tub, produeix una ona estacionària només per a determinades llargàries del tub. En aquesta situació hi ha una relació entre la freqüència de ressonància de l’ona sonora incident, la longitud del tub i la velocitat de propagació del so en l’aire. I si determinem experimentalment la longitud del tub i la freqüència de ressonància és possible obtenir la velocitat del so en l’aire

Determinació de l’acceleració de la gravetat i la velocitat del so en l’aire utilitzant senyals d’àudio

La realització d’experiments de física utilitzant noves tecnologies és sovint més atractiva per als estudiants que els experiments convencionals. En aquest treball usem la targeta de so d’un ordinador per a mesurar el temps que transcorre entre dos sons. Hem portat a terme dos experiments per a calcular l’acceleració de la gravetat, on hem utilitzat la targeta de so de l’ordinador i el programa Audacity de gravació i edició de sons. El primer experiment es basa en la cinemàtica del tir parabòlic d’un cos, mentre que el segon experiment està basat en la llei d’inducció de Faraday quan un imant cau per un tub no metàl·lic on hi ha espires enrotllades. D’aquesta manera, hem obtingut l’acceleració de la gravetat mitjançant un procediment diferent a l’habitual en els laboratoris de física. També hem demostrat experimentalment que el temps de caiguda d’un cos no depèn de la seua velocitat horitzontal inicial ni de la seua massa, error molt comú entre els estudiants

Staging Parkinson's Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life

Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD