Recent Advances in Rapid Synthesis of Non-proteinogenic Amino Acids from Proteinogenic Amino Acids Derivatives via Direct Photo-Mediated C-H Functionalization

Abstract

Non-proteinogenic amino acids have attracted tremendous interest for their essential applications in the realm of biology and chemistry. Recently, rising C-H functionalization has been considered an alternative powerful method for the direct synthesis of non-proteinogenic amino acids. Meanwhile, photochemistry has become popular for its predominant advantages of mild conditions and conservation of energy. Therefore, C-H functionalization and photochemistry have been merged to synthesize diverse non-proteinogenic amino acids in a mild and environmentally friendly way. In this review, the recent developments in the photo-mediated C-H functionalization of proteinogenic amino acids derivatives for the rapid synthesis of versatile non-proteinogenic amino acids are presented. Moreover, postulated mechanisms are also described wherever needed.

Keywords: C–H functionalization; non-proteinogenic amino acids; photo-mediated.

Figure 1

Selected examples of non-proteinogenic amino acids (NPAAs) as drugs (a), biotechnological tools (b) and catalysts (c).

Scheme 1

Photo-mediated C–H functionalization of proteinogenic amino acids (PAAs) toward the rapid synthesis of NPAAs.

Scheme 2

C(sp³)–H alkylation of Gly derivatives with N-alkyl-2,4,6-triphenylpyridinium salt (TPP) by the catalysis of iridium complex (a) and electron donor–acceptor (EDA) complex (b).

Scheme 3

C(sp³)–H alkylation of Gly-containing peptides with TPP by the catalysis of iridium complex (a) and EDA complex (b).

Scheme 4

C(sp³)–H alkylation of Gly derivatives (a) and Gly-containing peptides (b) with N-hydroxyphthalimide (NHP) esters. (c) Proposed mechanism.

Scheme 5

C(sp³)–H alkylation of Gly derivatives with N-alkoxyphthalimides.

Scheme 6

C(sp³)–H alkylation of Gly derivatives with silyl enol ethers.

Scheme 7

C(sp³)–H alkylation of Gly derivatives with α-angelicalactone.

Scheme 8

C(sp³)–H alkylation of Gly derivatives with enamines.

Scheme 9

C(sp³)–H alkylation of amino acids derivatives with 1,1-bis(phenylsulfonyl)ethylene (a) and tert-butyl acrylate (b).

Scheme 10

CO₂-activated tandem C(sp³)–H alkylation and intramolecular cyclization.

Scheme 11

C(sp³)–H alkylation of Trp-containing peptides with electron-deficient olefins.

Scheme 12

C(sp³)–H alkylation of Lys derivatives with alkyl bromides.

Scheme 13

C(sp³)–H alkylation of Met-containing peptides with alkyl bromides.

Scheme 14

C(sp³)–H alkylation of Gly derivatives with the β-keto esters.

Scheme 15

C(sp²)–H alkylation of Trp derivatives with alkyl bromides by the catalysis of ruthenium complex (a) and bithiophene (b).

Scheme 16

C(sp²)–H alkylation of His derivatives (a) and His-containing peptides (b) with 4-alkyl-1,4-dihydropyridines (DHP).

Scheme 17

C(sp²)–H alkylation of Trp derivatives with diazo esters.

Scheme 18

Intramolecular decarboxylative alkylation of Trp derivatives.

Scheme 19

Intramolecular C(sp³)–H benzylation of proline derivatives (a) and other amino acids derivatives (b) with phenyl ketones.

Scheme 20

Intermolecular C(sp³)–H benzylation of Gly derivatives with phenyl ketones.

Scheme 21

Intermolecular C(sp³)–H benzylation of Gly derivatives with aldehydes.

Scheme 22

C(sp³)–H benzylation of Pro derivative with benzylidenemalononitrile.

Scheme 23

Catalyst-free C(sp²)–H benzylation of Trp derivatives with benzyl bromide through the electron donor–acceptor (EDA) complex.

Scheme 24

C(sp²)–H benzylation of Trp derivatives with tricyclic benzyl bromide.

Scheme 25

C(sp³)–H allylation of amino acid derivatives with allyltributyltin.

Scheme 26

C(sp²)–H trifluoromethylation of Tyr derivatives with CF₃I (a) and NaSO₂CF₃, (b) Tyr-containing peptides with NaSO₂CF₃ (c).

Scheme 27

C(sp²)–H trifluoromethylation of Trp derivatives.

Scheme 28

C(sp²)–H trifluoromethylation of Trp-containing peptides with NaSO₂CF₃.

Scheme 29

C(sp²)–H fluorobutylation (a) and gem-difluoromethylation (b) of Trp derivatives.

Scheme 30

C(sp²)–H phosphonoacetylation of Trp derivative with 2-bromophosphonoacetic ester.

Scheme 31

C(sp²)–H diazomethylation of Phe derivative with benziodoxolone.

Scheme 32

C(sp³)–H alkenylation of Pro derivative with bis(phenylsulfonyl)ethylene.

Scheme 33

C(sp³)–H alkenylation of Met and Leu derivatives with alkenylboronic acid.

Scheme 34

C(sp³)–H alkynylation of amino acids derivatives with 1-tosyl-2-(trimethylsilyl)acetylene (a) and ethynylbenziodoxolone (b).

Scheme 35

Intramolecular C(sp³)–H acylation of Ala and Val derivatives with N-succinimides.

Scheme 36

Intermolecular C(sp³)–H acylation of Pro derivative with sulfonyl oxime.

Scheme 37

C(sp²)–H acylation of Trp derivatives with aldehydes.

Scheme 38

C(sp³)–H cyanation of Pro (a) and Gly (b) derivatives.

Scheme 39

C(sp³)–H cyanation of Met derivatives through the cooperative visible-light photoredox/phosphate acid catalysis.

Scheme 40

C(sp³)–H arylation of Gly derivatives with indoles through the cooperative catalysis of photoredox and Lewis acid.

Scheme 41

C(sp³)–H arylation of Gly derivatives with indoles through the cooperative catalysis of photoredox and cobalt.

Scheme 42

C(sp³)–H arylation of Gly derivatives with arenes.

Scheme 43

C(sp³)–H arylation of Pro (a) and Leu (b) derivatives with benzothiazole.

Scheme 44

C(sp³)–H arylation of Pro derivative with aryl bromide.

Scheme 45

C(sp²)–H heteroarylation of Trp, Tyr, and His derivatives with 5-bromouracil.

Scheme 46

C(sp²)–H heteroarylation of Trp derivative with 5-bromo-1,3-dimethyluracils.

Scheme 47

C(sp³)–H azidation of Leu-containing dipeptides with azidoiodane.

Scheme 48

C(sp³)–H amination of Pro (a), Phe, and Leu (b) derivatives with triflamide. (c) Proposed mechanism.

Scheme 49

C(sp²)–H imidation of Tyr derivatives with N-chlorophthalimide.

Scheme 50

C(sp²)–H amination of Phe derivatives (a) and Phe-containing peptides (b) with alkyl amines.

Scheme 51

C(sp²)–H imidation of Tyr derivatives with phthalimide.

Scheme 52

Intramolecular C(sp³)–H dithiocarbamylation of Val derivative.

Scheme 53

C(sp²)–H sulfenylation of Trp derivative with thiophenol.

Scheme 54

C(sp³)–H hydroxylation of Cys derivative.

Scheme 55

C(sp³)–H hydroxylation of Val (a) and Leu (b) derivatives with hydroxyl perfluorobenziodoxole (PFBl–OH).

Scheme 56

C(sp³)–H hydroxylation of Val derivative through tandem bromination/atom transfer/cyclization.

Scheme 57

C(sp³)–H hydroxylation of Leu derivative with water.

Scheme 58

C(sp²)–H phosphonylation of Trp derivative with triethyl phosphite.

Scheme 59

C(sp³)–H fluorination of Phe-containing peptides with Selectfluor.

Scheme 60

C(sp³)–H fluorination of Leu and Ile derivatives (a) and Leu-containing peptides (b) with N-fluorobenzenesulfonimide (NSFI).

Scheme 61

C(sp³)–H chlorination (a) and bromination (b) of Leu derivatives with Zhdankin reagent.

Scheme 62

Intramolecular C(sp³)–H chlorination of Val derivative.