Applications of fluorine-containing amino acids for drug design

Fluoroalkylation of Diazo Compounds with Diverse Rfn Reagents

“…In 2012, Hu and coworkers reported a copper-mediated trifluoromethylation of α-diazo esters (1) with TMSCF 3 , which represent the first fluoroalkylation of diazo compounds (Scheme 1). [10a] In this process, [CuCF 3 ] intermediates are first formed in situ from a mixture of CuI, TMSCF 3 and CsF (1.0 : 1.1 : 1.1), and react with α-diazo substrates to produce carbene-inserted complexes (11). These complexes are then quenched with water to provide α-trifluoromethyl esters (2) as the final products.…”

“…Additionally, the "Fischer carbene like" properties of difluorocarbene were explored in this work, which opened new opportunity for difluorocarbene in organic synthesis. [16] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 Very recently, Hu and coworkers reported a Cu-catalyzed gem-bis(trifluoromethyl) olefination of α-diazo esters (47) using TMSCF 3 as the sole fluorocarbon source (Scheme 7). [17] The reaction proceeded smoothly in a one-pot procedure, involving four successive steps (carbene migratory insertion, β-fluoride elimination, and two consecutive addition-elimination steps), and provided a number of gem-bis(trifluoromethyl)alkenes (48) as the major products in moderate to good yields.…”

“…The SeCF 3 moiety is a special fluorine-containing functional group, [37] which not only endows the target molecules with useful lipophilicity and membrane permeability, but also has potentials of changing their bioactivities. Due to the limited types of SeCF 3 [26] The reaction was tolerable to air and water, and gave the expected trifluoromethyl selenoethers (158) in good yields under neutral conditions. This protocol was thought to be suitable for both of the late-stage trifluoromethylthiolation and trifluoromethylselenolation of drug-like molecules.…”

“…[1,2] At present, there have been 20-30% of pharmaceuticals and approximately 40% of agrochemicals on the market containing at least one fluorine atom, and these percentages are growing each year. [3] Moreover, fluorinated polymers have played an indispensable role in modern life, which have found widespread applications as thermoplastics, elastomers, weatherproof coatings, biomedical materials, membranes, and others. [4] Fluorine can also be used as a diagnostic tool in positron emission tomography (PET) that employs 18 F-labeled radiotracers and in 19 F magnetic resonance imaging (MRI) that relies on polyfluorinated molecules.…”

Influence of Fluorination on Single-Molecule Unfolding and Rupture Pathways of a Mechanostable Protein Adhesion Complex

“…[1][2][3] In particular, the unique chemical characteristics of fluorine can alter amino acid side chain properties including hydrophobicity, acidity, and reactivity. [4][5][6] Incorporation of fluorinated analogues of aliphatic amino acids including leucine (LEU), isoleucine (ILE), and valine (VAL) imparts increased hydrophobicity [7][8][9] and is typically marginally disruptive to native protein structure 10 . Isosteric hydrogen-to-fluorine replacement can therefore alter the protein folding energy landscape, in some cases increasing thermodynamic stability but in other cases weakening it.…”