Recent advances in the synthesis of fluorinated amino acids and peptides

Abstract

The site-selective modification of amino acids, peptides, and proteins has always been an intensive topic in organic synthesis, medicinal chemistry, and chemical biology due to the vital role of amino...

Visible‐Light‐Driven Three‐Component Reaction of Unactivated Alkenes Enables Access to Monofluoro γ‐Amino Acids

“…N-free protected quinoxalinone was found to be well-suitable for this transformation, generating the product (5) in 75 %. Additionally, a variety of N-protecting groups including phenyl (6), n-butyl (7), cyclopropylmethyl (8), tert-butoxycarbonylmethyl (9), 2-oxo-2phenylethyl (10), and benzyl (11) were well tolerated in this reaction to provide the desired γ-FAAs derivatives in good yield. A benzo[f]quinoxalin-2(1H)-one was also an acceptor to afford (12) in 42 % yield.…”

“…In recent years, several light‐triggered multicomponent reactions have been developed for the efficient synthesis of fluorinated quinoxalin‐2‐one derivatives, however, none of those involve the construction of building blocks for fluorine‐containing quinoxaline‐2‐ones amino acid (Scheme 1a) [9] . Multicomponent reactions are a well‐established strategy for the preparation of some complex fluorine‐containing amino acids that are otherwise difficult to synthesize via conventional methods (Scheme 1b) [10] . In 2016, Zhang's group reported an example of nickel‐catalyzed multicomponent difluoroalkylarylation of enamides that enables access to protected γ‐amino acids through a chelation‐assisted strategy [11] .…”

“…[9] Multicomponent reactions are a well-established strategy for the preparation of some complex fluorine-containing amino acids that are otherwise difficult to synthesize via conventional methods (Scheme 1b). [10] In 2016, Zhang's group reported an example of nickel-catalyzed multicomponent difluoroalkylarylation of enamides that enables access to protected γ-amino acids through a chelation-assisted strategy. [11] Subsequently, this strategy was extended to the conversion of alkenes to simple enamides and endocyclic enecarbamates by using different aryl reagents.…”

Direct Assembly of Vinyl Fluorinated Isoquinolines Via Rh(III)-Catalyzed [4 + 2] Annulation

“…Because the physiological activity of organic compounds could be ameliorated by installing fluorine atoms or fluorinated units in suitable positions, fluorinated building blocks have been broadly exploited in medicinal chemistry and different stages of drug discovery . In particular, monofluoroalkenes have been characterized as nonhydrolyzable peptide mimics, − which are confirmed to have innate antibacterial and various antitumor effects due to their electronic and geometric resemblance .…”

On the Selectivity in the Synthesis of 3-Fluoropiperidines Using BF3-Activated Hypervalent Iodine Reagents

“…Besides explicit ligand–receptor non-covalent interactions in which C–F bonds can be engaged, such bonds are highly useful in biasing conformational ensembles of flexible alkyl chains (Figure C), which is extremely relevant for catalytic synthetic methods, , as well as in drug development (Figure D) . Accordingly, predictive, effective, and modular methodologies for introducing stereodefined C–F bonds are strongly desired. , In this light, the Glorius group reported a highly diastereoselective Rh-catalyzed transformation of (poly)­fluorinated pyridines into all- cis -(poly)­fluorinated piperidines . On the other hand, Liu’s group developed highly regioselective alkene fluoroamination protocols utilizing high-valent palladium chemistry for the preparation of β-fluorinated piperidines , and pyrrolidines (Figure ).…”