Synthesis of chiral atropisomeric phosphonates and diphosphines

Depuis une trentaine d'année, l'obtention de composés chiraux énantiopurs tient un rôle prépondérant dans la synthèse de molécules biologiquement actives, tout particulièrement dans les domaines de la pharmacie de l'agrochimie et de la parfumerie. Cet engouement pour la synthèse énantiosélective a conduit à la mise au point de multiples ligands chiraux et notamment les diphosphines chirales par atropoisomérie initiées par les travaux de Noyori et Takaya. Nous nous sommes intéressés à la synthèse de nouveaux ligands hétérocycliques bidents et chiraux par atropoisomérie par des voies de synthèse originale où une double construction des hétérocycles sera mise en œuvre dans l'étape clé. En parallèle, nous avons aussi développé une approche de synthèse permettant l'obtention de mono et bis phosphonates atropochiraux utilisant des allènes comme précurseurs de la synthèse.Atropisomeric diphosphine ligands play a crucial role in the synthesis of enantiopur molecules, particularly in pharmaceutical, agrochemical and flavors industries. Growing demand in asymmetric synthesis, impose to develop news ligands by rapid, economic and effective strategies of synthesis. This optically pure ligand was combined with multiples transition metal to form catalyst what will have used wide variety of entioselective reaction type.Over the past few years, a new family of ligands has emerged, possessing biheterocyclic skeleton and thus allowing the introduction of different steric and electronic interactions. We will report a efficient syntheses of the new atropisomeric five-membered heterocyclic diphosphines with original strategy of synthesis whose the main stages consist in a double heterocyclic construction. In the second part, we will develop an approach permitting to obtain atropochiral phosphonates with a similar strategy of synthesis from allenylphosphine oxides or allenylphosphonates as precursors

Driving the Morita-Baylis-Hillman Reaction to a Multicomponent Organic Transformation

International audienceThe combination of a trivalent phosphorus reagent with an aldehyde and a Michael olefin in the presence of water led to the formation of functionalized phosphine oxides. This approach turned the Lewis base organocatalyzed Morita-Baylis-Hillman reaction into a multicomponent organic transformation to provide rapid access to polyfunctionalized molecules

Synthesis of Unnatural Phosphonosugar Analogues.

International audienceThe first synthesis of new cyclic phosphonates (phostones), analogues of pentafuranoses containing a phosphorus atom in place of the anomeric carbon in the deoxyribose and deoxyxylose series, is described. Two methods, of respectively six and seven steps, were developed in parallel, and each gave the racemic phosphonosugars in good yields. Compounds analogous to the alpha and beta anomers were isolated and fully characterized by NMR spectroscopy

Double [3 + 2]-dimerisation cascade synthesis of bis(triazolyl)bisphosphanes, a new scaffold for bidentate bisphosphanes

International audienceA highly convergent synthesis of bis(triazolylphosphane oxides) was developed by a tandem copper-mediated Huisgen reaction–oxidative coupling. The phosphane oxides were reduced by trichlorosilane and the coordination of the resulting bisphosphanes was studied with various transition metals

Premorbid aspirin use is not associated with lower mortality in older inpatients with SARS-CoV-2 pneumonia

Platelet aggregation has been associated with COVID-19 pathogenesis. In older patients hospitalized for SARS-CoV-2 pneumonia, we aimed to investigate the association between aspirin use before admission and the risk of in-hospital all-cause mortality. We performed a retrospective international cohort study in five COVID-19 geriatric units in France and Switzerland. Among 1,357 consecutive hospitalized patients aged 75 or older and testing positive for SARS-CoV-2, we included 1,072 with radiologically confirmed pneumonia. To adjust for confounders, a propensity score for treatment was created, and stabilized inverse probability of treatment weighting (SIPTW) was applied. To assess the association between aspirin use and in-hospital 30-day mortality, SIPTW-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed. Of the 1047 patients with SARS-CoV-2 pneumonia and median age 86 years, 301 (28.7%) were taking aspirin treatment before admission. One hundred forty-seven (34.3%) patients who had taken aspirin died in hospital within 1 month vs 118 patients (30.7%) without aspirin. After SIPTW, aspirin treatment was not significantly associated with lower mortality (adjusted hazard ratio: 1.10 [0.81-1.49], P = .52). Moreover, patients on aspirin had a longer hospital stay and were more frequently transferred to the intensive care unit. In a large multicenter cohort of older inpatients with SARS-CoV-2 pneumonia, aspirin use before admission did not appear to be associated with an improved prognosis

Poison control centres and alternative forms of communication: comparison of response rates between text message and telephone follow-up

INTRODUCTION: In recent years, the number of patients managed by poison control centres (PCCs) has increased without a proportional increase in the number of physicians. To improve efficiency without neglecting patient follow-up, some PCCs have begun using text messages. We evaluated the difference in response rates between text messaging and traditional telephone follow-up. MATERIALS AND METHODS: This retrospective, monocentric, non-randomised cohort study was conducted using data from calls made by the New Aquitaine PCC between February 27, 2019, and March 31, 2019. Patients were contacted up to three times by a phone call or short message service (SMS). RESULTS: For the analysis, 823 patients were included. At the end of follow-up, the response rates were similar in the phone call and SMS group (94 vs. 94%; p = 0.76) with median [interquartile range] response times of 0 min [0; 27 min] and 29 min [6; 120 min], respectively. The response rates did not differ in subgroups stratified according to sex, self-poisoning vs. relative response, age class, and solicitation during working hours vs. outside of working hours (all p > 0.5). Moreover, health practitioners required 2.4-fold more time to call than to send text messages (p < 0.001), and all practitioners were satisfied or very satisfied with text messaging implementation. CONCLUSION: Patients had good adherence to text messages. Text messages are easy to use, rapid, and allow the physician to easily prioritise follow-up without occupying the emergency line. Additionally, the costs of installation and maintenance are low for text message systems; these low costs facilitate the implementation of such services in various medical situations