General Procedure for Carbon Isotope Labeling of Linear Urea Derivatives with Carbon Dioxide

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 14C and 11C. 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 [14C]CO2 screening that allowed to investigate the tolerance of the procedure with most representative heterocycles and functional groups found in FDA approved drugs.

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

10.26434/chemrxiv.13519091 ◽

2021 ◽

Author(s):

Victor Babin ◽

Antoine Sallustrau ◽

Olivier Loreau ◽

Fabien Caillé ◽

Amélie Goudet ◽

...

Keyword(s):

Carbon Dioxide ◽

Full Article ◽

Carbon Isotope ◽

Carbon Isotopes ◽

Isotope Labeling ◽

General Procedure ◽

Urea Derivatives ◽

Living Organisms ◽

Approved Drugs ◽

Fda Approved Drugs

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 14C and 11C. 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 [14C]CO2 screening that allowed to investigate the tolerance of the procedure with most representative heterocycles and functional groups found in FDA approved drugs.

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Carbon isotope labeling of carbamates by late-stage [11C], [13C] and [14C]carbon dioxide incorporation

Chemical Communications ◽

10.1039/d0cc05031h ◽

2020 ◽

Vol 56 (78) ◽

pp. 11677-11680

Author(s):

Antonio Del Vecchio ◽

Alex Talbot ◽

Fabien Caillé ◽

Arnaud Chevalier ◽

Antoine Sallustrau ◽

...

Keyword(s):

Carbon Dioxide ◽

Carbon Isotope ◽

Carbon Isotopes ◽

Late Stage ◽

Building Block ◽

Isotope Labeling

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.

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Investigation on the Stoichiometry of Carbon Dioxide in Isotope-Exchange Reactions with Phenylacetic Acids

Synlett ◽

10.1055/s-0040-1720447 ◽

2021 ◽

Author(s):

Davide Audisio ◽

Alex Talbot ◽

Antoine Sallustrau ◽

Amélie Goudet ◽

Frédéric Taran

Keyword(s):

Carbon Dioxide ◽

Carbon Isotope ◽

Isotope Exchange ◽

Isotope Labeling ◽

Exchange Reactions ◽

Major Interest ◽

Carbon Dioxide Co2 ◽

Dilution Effects ◽

Product Outcome ◽

Insight Into

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.

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Studies of photo-synthesis in fresh-water algœ. —1. The fixation of both carbon and nitrogen from the atmosphere to form organic tissue by the green plant cell. 2. Nutrition and growth produced by high gaseous dilutions of simple organic compounds, such as formaldehyde and methylic alcohol. 3. Nutrition and growth by means of high dilutions of carbon dioxide and oxides of nitrogen without access to atmosphere

Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character ◽

10.1098/rspb.1920.0011 ◽

1920 ◽

Vol 91 (638) ◽

pp. 201-215 ◽

Cited By ~ 5

Keyword(s):

Carbon Dioxide ◽

Organic Compounds ◽

Inorganic Nitrogen ◽

Living Organism ◽

Green Plant ◽

Oxides Of Nitrogen ◽

Carbon And Nitrogen ◽

High Dilutions ◽

Living Organisms ◽

Organic Tissue

The two most primæval and most fundamental chemical processes for living organisms are those two in which their living substance is synthesised from inorganic sources with uptake of energy. By one of these carbon is built into organic compounds, starting with the oxidised carbon dioxide of the atmosphere and utilising the energy of sunlight. The source of the inorganic nitrogen, which in the second is likewise built into organic forms in the amino-acids and proteins, is more obscure, and has in the course of 150 years led to much disputation. In the present and succeeding papers evidence will be adduced that the source of the nitrogen utilised by the plant does not lie in the soil (although a luxury or luxus supply may be given from the soil), but in the air, and that the reaction by which the atmospheric nitrogen and oxygen are made reactive is a photo-synthetic one, in which the energy of sunlight is absorbed and converted into chemical form as nitrites in the green cell. This view places these two processes of carbon and nitrogen assimilation upon the same basis, and make them coeval in the process of evolution; this, as will presently be pointed out, must have been the case, in order that any living organism could ever have appeared upon the earth.

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