scholarly journals Robust and General Procedure for Carbon Isotope Labeling of Linear Urea Derivatives with Carbon Dioxide

Author(s):  
Victor Babin ◽  
Antoine Sallustrau ◽  
Olivier Loreau ◽  
Fabien Caillé ◽  
Amélie Goudet ◽  
...  

Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. Despite recent advances in the field, the development of robust and general technologies remains a significant task. This full article reports on a general approach to label urea derivatives with all carbon isotopes, including <sup>14</sup>C and <sup>11</sup>C. Based on a Staudinger aza-Wittig sequence, it provides access to all aliphatic/aromatic urea combinations as well as to semicarbazides, sulfonylureas, hydroxyl ureas, and simple terminal ureas. A de-risking approach was developed to evaluate the robustness of the reaction. This technology is based on [<sup>14</sup>C]CO<sub>2</sub> screening that allowed to investigate the tolerance of the procedure with most representative heterocycles and functional groups found in FDA approved drugs.

2021 ◽  
Author(s):  
Victor Babin ◽  
Antoine Sallustrau ◽  
Olivier Loreau ◽  
Fabien Caillé ◽  
Amélie Goudet ◽  
...  

Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. Despite recent advances in the field, the development of robust and general technologies remains a significant task. This full article reports on a general approach to label urea derivatives with all carbon isotopes, including <sup>14</sup>C and <sup>11</sup>C. Based on a Staudinger aza-Wittig sequence, it provides access to all aliphatic/aromatic urea combinations as well as to semicarbazides, sulfonylureas, hydroxyl ureas, and simple terminal ureas. A de-risking approach was developed to evaluate the robustness of the reaction. This technology is based on [<sup>14</sup>C]CO<sub>2</sub> screening that allowed to investigate the tolerance of the procedure with most representative heterocycles and functional groups found in FDA approved drugs.


2021 ◽  
Author(s):  
Victor Babin ◽  
Antoine Sallustrau ◽  
Olivier Loreau ◽  
Fabien Caillé ◽  
Amélie Goudet ◽  
...  

Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. This article reports on a general approach...


2020 ◽  
Vol 56 (78) ◽  
pp. 11677-11680
Author(s):  
Antonio Del Vecchio ◽  
Alex Talbot ◽  
Fabien Caillé ◽  
Arnaud Chevalier ◽  
Antoine Sallustrau ◽  
...  

A procedure which allows labelling cyclic carbamates with all carbon isotopes has been developed. This protocol valorizes carbon dioxide, the universal building block for radiolabeling. A series of pharmaceuticals were obtained and a disconnection/reconnection strategy was implemented.


Synlett ◽  
2021 ◽  
Author(s):  
Davide Audisio ◽  
Alex Talbot ◽  
Antoine Sallustrau ◽  
Amélie Goudet ◽  
Frédéric Taran

AbstractThe functionalization of carbon dioxide (CO2) as a C1 building block has attracted enormous attention. Carboxylation reactions, in particular, are of major interest for applications in isotope labeling. Due to the inexpensive nature of CO2, information about its stoichiometric use is generally unavailable in the literature. Because of the rarity and limited availability of CO2 isotopomers, this parameter is of concern for applications in carbon-isotope labeling. We investigated the effects of the stoichiometry of labeled CO2 on carbon isotope exchange of phenyl­acetic acids. Both thermal and photocatalytic procedures were studied, providing insight into product outcome and isotope incorporation. Preliminary results on isotope-dilution effects of carbonate bases in photocatalytic carboxylation reactions have also been obtained.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daijun Fan ◽  
Xuanlong Shan ◽  
Yousif M. Makeen ◽  
Wentong He ◽  
Siyuan Su ◽  
...  

AbstractThis paper presents new research on a lacustrine anoxic event (LAE). These data include stable carbon isotope (δ13Corg), pyrite sulfur isotope (δ34Spy), trace element and biomarker ratios from the Hongmiaozi Basin (North China) and unravel the response of continental lakes under the influence of early Aptian extreme climate conditions. According to the stratigraphic chronology (122–118 Ma) and carbon isotope correlations, terrestrial sediment was influenced by the early Aptian Oceanic Anoxic Event (OAE1a). The results show that the Xiahuapidianzi Group experienced a significant warming process under negative excursions in carbon isotopes due to the influence of increased carbon dioxide partial pressure (pCO2). The climate varied from warm and humid to hot and arid (high Sr/Cu, low Rb/Sr, calcareous mudstone), the evaporation and salinity increased (high Sr/Ba and B/Ga), and land input sources decreased (low Zr, Ti and Th). Moreover, high total organic carbon (TOC) content was source from bacteria, algae (n-alkanes), and euxinic depositional environments (Pr/Ph, Cu/Zn and U V Mo). In the stage of continuous carbon isotopes positive excursion, organic matter accumulated rapidly. A paleolake environment model has provided a better understanding of current global climate issues under global warming caused by increased carbon dioxide concentrations.


Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
H Houson ◽  
J Schlesser ◽  
J Beverage ◽  
V Macherla ◽  
E Esquenazi

2020 ◽  
Vol 27 ◽  
Author(s):  
Firoz Anwar ◽  
Salma Naqvi ◽  
Fahad A. Al-Abbasi ◽  
Nauroz Neelofar ◽  
Vikas Kumar ◽  
...  

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.


2018 ◽  
Vol 15 (2) ◽  
pp. 208-220 ◽  
Author(s):  
Vaibhav Mishra ◽  
Tejpal Singh Chundawat

Background: Substituted piperazine heterocycles are among the most significant structural components of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is the key tool for the synthesis of these compounds. Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters. Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4 substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation in catalyst design and improvements in reaction conditions. This review gives an overview of recent utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.


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