Jean-Pierre Begue

One-pot synthesis of non-symmetric tetraoxanes with the H2O2/MTO/fluorous alcohol system☆

Abstract 1,2,4,5-Tetraoxanes, potent antimalarial drugs, were selectively synthesized in fluorous alcohols (2,2,2-trifluoroethanol–TFE and 1,1,1,3,3,3-hexafluoro-2-propanol–HFIP). A use of these solvents enabled for the first time a one-pot synthesis of non-symmetric tetraoxanes in good yields from simple ketones and aldehydes with 2 equiv. of 30% hydrogen peroxide and 0.1 mol% of methyltrioxorhenium (MTO).

Methyltrioxorhenium-catalysed epoxidation of alkenes: enhancement of reactivity in hexafluoro-2-propanol

Abstract Methyltrioxorhenium-catalysed epoxidation of alkenes with hydrogen peroxide can be improved by using hexafluoro-2-propanol as a solvent. Quantitative conversions of cyclic and terminal olefins can be obtained with only 30% H 2 O 2 and 0.1 mol% of catalyst.

Ring-Opening of 1-CF3-Substituted Epoxy Ethers with Carboxylic, Thiocarboxylic, and Phosphinic Acids in Basic Medium and in Hexafluoro-2-propanol

Ring-opening of 1-CF3-substituted epoxy ethers with carboxylic acids was achieved in Et3N as solvent, and α-CF3-substituted acyloins and corresponding esters were obtained in good yields. In hexafluoro-2-propanol (HFIP) as solvent, the carboxylic acids acted as nucleophiles, and α-carbonyloxy trifluoromethyl ketones were isolated in good yields. After reduction, CF3-substituted glycols were obtained as monoesters on one or the other hydroxy group. This reaction also allowed the preparation of α-carbonylsulfanyl- and α-phosphoryloxy trifluoromethyl ketones and corresponding alcohols. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Biological Impacts of Fluorination: Pharmaceuticals Based on Natural Products

Publisher Summary This chapter focuses on the recent advances in the fluorinated analogues of natural products developed as pharmaceuticals. These mainly concern fluorine-substituted nucleosides, alkaloids, macrolides, steroids, amino acids, and prostaglandins. Among the numerous marketed pharmaceuticals in the world, more than 150 drugs are fluorinated compounds. The specific properties of the fluorine atom, such as its strong electronegativity, small size, and low polarisability of the C–F bond, can have considerable impact on the behavior of a small molecule in a biological environment. The introduction of fluorine atoms into a molecule has an impact on the physical and chemical properties of this molecule, with deep consequences on the biological properties. The absorption, distribution, recognition, and interaction or reaction processes with the biological target, as well as the metabolism and the elimination of this molecule, are affected. This possibility to modify or to modulate the pharmacological profile of a molecule by inserting fluorine atoms clearly explains why bioorganic and medicinal chemistry of fluorine has become so important, and why many drugs and pesticides are fluorinated compounds. Fluorinated groups (F, CF2, etc.) are isosteric or isopolar of various functional groups; they can mimic them in the interaction processes with biological macromolecules. They can also interact afterwards with the target, because of the specific reactivity of the fluorinated molecule. This explains the important role played by the incorporation of fluorine atoms in the design of receptor ligands and enzyme inhibitors: substrate analogues, transition state analogues, and based-mechanism inhibitors.Publisher Summary This chapter focuses on the recent advances in the fluorinated analogues of natural products developed as pharmaceuticals. These mainly concern fluorine-substituted nucleosides, alkaloids, macrolides, steroids, amino acids, and prostaglandins. Among the numerous marketed pharmaceuticals in the world, more than 150 drugs are fluorinated compounds. The specific properties of the fluorine atom, such as its strong electronegativity, small size, and low polarisability of the C–F bond, can have considerable impact on the behavior of a small molecule in a biological environment. The introduction of fluorine atoms into a molecule has an impact on the physical and chemical properties of this molecule, with deep consequences on the biological properties. The absorption, distribution, recognition, and interaction or reaction processes with the biological target, as well as the metabolism and the elimination of this molecule, are affected. This possibility to modify or to modulate the pharmacological profile of a molecule by inserting fluorine atoms clearly explains why bioorganic and medicinal chemistry of fluorine has become so important, and why many drugs and pesticides are fluorinated compounds. Fluorinated groups (F, CF2, etc.) are isosteric or isopolar of various functional groups; they can mimic them in the interaction processes with biological macromolecules. They can also interact afterwards with the target, because of the specific reactivity of the fluorinated molecule. This explains the important role played by the incorporation of fluorine atoms in the design of receptor ligands and enzyme inhibitors: substrate analogues, transition state analogues, and based-mechanism inhibitors.

Synthesis of trifluoromethylated diterpenoids

Abstract Intramolecular carbonyl-ene reaction of ω-unsaturated trifluoromethyl ketones have been described as a stereoselective approach to 5-, 6-, 7- and 8- membered trifluoromethyl cyclanols. The use of this strategy is illustrated by the synthesis of trifluoromethylated analogs of diterpenoids by a tandem carbonyl-ene/cycloalkylation reaction: Influence of Lewis acid and reaction conditions of the outcome of this reaction (product distribution, stereoselectivity) is discussed.

Biological Impacts of Fluorination

Publisher Summary This chapter focuses on the recent advances in the fluorinated analogues of natural products developed as pharmaceuticals. These mainly concern fluorine-substituted nucleosides, alkaloids, macrolides, steroids, amino acids, and prostaglandins. Among the numerous marketed pharmaceuticals in the world, more than 150 drugs are fluorinated compounds. The specific properties of the fluorine atom, such as its strong electronegativity, small size, and low polarisability of the C–F bond, can have considerable impact on the behavior of a small molecule in a biological environment. The introduction of fluorine atoms into a molecule has an impact on the physical and chemical properties of this molecule, with deep consequences on the biological properties. The absorption, distribution, recognition, and interaction or reaction processes with the biological target, as well as the metabolism and the elimination of this molecule, are affected. This possibility to modify or to modulate the pharmacological profile of a molecule by inserting fluorine atoms clearly explains why bioorganic and medicinal chemistry of fluorine has become so important, and why many drugs and pesticides are fluorinated compounds. Fluorinated groups (F, CF2, etc.) are isosteric or isopolar of various functional groups; they can mimic them in the interaction processes with biological macromolecules. They can also interact afterwards with the target, because of the specific reactivity of the fluorinated molecule. This explains the important role played by the incorporation of fluorine atoms in the design of receptor ligands and enzyme inhibitors: substrate analogues, transition state analogues, and based-mechanism inhibitors.Publisher Summary This chapter focuses on the recent advances in the fluorinated analogues of natural products developed as pharmaceuticals. These mainly concern fluorine-substituted nucleosides, alkaloids, macrolides, steroids, amino acids, and prostaglandins. Among the numerous marketed pharmaceuticals in the world, more than 150 drugs are fluorinated compounds. The specific properties of the fluorine atom, such as its strong electronegativity, small size, and low polarisability of the C–F bond, can have considerable impact on the behavior of a small molecule in a biological environment. The introduction of fluorine atoms into a molecule has an impact on the physical and chemical properties of this molecule, with deep consequences on the biological properties. The absorption, distribution, recognition, and interaction or reaction processes with the biological target, as well as the metabolism and the elimination of this molecule, are affected. This possibility to modify or to modulate the pharmacological profile of a molecule by inserting fluorine atoms clearly explains why bioorganic and medicinal chemistry of fluorine has become so important, and why many drugs and pesticides are fluorinated compounds. Fluorinated groups (F, CF2, etc.) are isosteric or isopolar of various functional groups; they can mimic them in the interaction processes with biological macromolecules. They can also interact afterwards with the target, because of the specific reactivity of the fluorinated molecule. This explains the important role played by the incorporation of fluorine atoms in the design of receptor ligands and enzyme inhibitors: substrate analogues, transition state analogues, and based-mechanism inhibitors.

Chapter 13 – Biological Impacts of Fluorination: Pharmaceuticals Based on Natural Products

Publisher Summary This chapter focuses on the recent advances in the fluorinated analogues of natural products developed as pharmaceuticals. These mainly concern fluorine-substituted nucleosides, alkaloids, macrolides, steroids, amino acids, and prostaglandins. Among the numerous marketed pharmaceuticals in the world, more than 150 drugs are fluorinated compounds. The specific properties of the fluorine atom, such as its strong electronegativity, small size, and low polarisability of the C–F bond, can have considerable impact on the behavior of a small molecule in a biological environment. The introduction of fluorine atoms into a molecule has an impact on the physical and chemical properties of this molecule, with deep consequences on the biological properties. The absorption, distribution, recognition, and interaction or reaction processes with the biological target, as well as the metabolism and the elimination of this molecule, are affected. This possibility to modify or to modulate the pharmacological profile of a molecule by inserting fluorine atoms clearly explains why bioorganic and medicinal chemistry of fluorine has become so important, and why many drugs and pesticides are fluorinated compounds. Fluorinated groups (F, CF2, etc.) are isosteric or isopolar of various functional groups; they can mimic them in the interaction processes with biological macromolecules. They can also interact afterwards with the target, because of the specific reactivity of the fluorinated molecule. This explains the important role played by the incorporation of fluorine atoms in the design of receptor ligands and enzyme inhibitors: substrate analogues, transition state analogues, and based-mechanism inhibitors.Publisher Summary This chapter focuses on the recent advances in the fluorinated analogues of natural products developed as pharmaceuticals. These mainly concern fluorine-substituted nucleosides, alkaloids, macrolides, steroids, amino acids, and prostaglandins. Among the numerous marketed pharmaceuticals in the world, more than 150 drugs are fluorinated compounds. The specific properties of the fluorine atom, such as its strong electronegativity, small size, and low polarisability of the C–F bond, can have considerable impact on the behavior of a small molecule in a biological environment. The introduction of fluorine atoms into a molecule has an impact on the physical and chemical properties of this molecule, with deep consequences on the biological properties. The absorption, distribution, recognition, and interaction or reaction processes with the biological target, as well as the metabolism and the elimination of this molecule, are affected. This possibility to modify or to modulate the pharmacological profile of a molecule by inserting fluorine atoms clearly explains why bioorganic and medicinal chemistry of fluorine has become so important, and why many drugs and pesticides are fluorinated compounds. Fluorinated groups (F, CF2, etc.) are isosteric or isopolar of various functional groups; they can mimic them in the interaction processes with biological macromolecules. They can also interact afterwards with the target, because of the specific reactivity of the fluorinated molecule. This explains the important role played by the incorporation of fluorine atoms in the design of receptor ligands and enzyme inhibitors: substrate analogues, transition state analogues, and based-mechanism inhibitors.