Modification of glycine-containing peptides induced by visible light

Abstract

Glycine residues in peptides have been converted into residues of a variety of branched amino-acids through the use of an appropriate reagent and visible light.

Free-Radical Reactions in the Synthesis of α-Amino Acids and Derivatives

“…Despite their stability, captodative radicals still undergo radical coupling reactions at rates which are diffusion controlled. , Under these conditions the nature of the alkylating agent should not affect the ratio of products of reactions of the dipeptide derivative 44f . As expected, therefore, when using visible light, biacetyl, and di- tert -butyl peroxide, with p -methoxytoluene and acetic acid or acetic anhydride, the derivatives of tyrosine 44h and 45h and aspartic acid 44i and 45i were each obtained in equal ratios …”

“…Accordingly, reaction with 4-methoxytoluene, in place of toluene, resulted in the conversion of glycine derivatives to the corresponding tyrosine derivatives (Scheme ). In other variations of this procedure, replacing toluene with 4-fluorotoluene, or acetic acid or acetic anhydride, resulted in the conversion of glycine derivatives to the 4-fluorophenylalanine and aspartic acid analogues 9 and 10 , respectively. , In each of these reactions it was necessary to use a large excess of the alkylating agent, in order to obtain the necessary balance between hydrogen atom transfer from that agent and the glycine derivative.

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“…In turn, this can be attributed to the decreased dative stabilization of the radical 46c by the trifluoroacetamido substituent, compared to the effect of the acetamido group on the radical 46b . Again the situation is more complicated than this simple interpretation would indicate; however, as the reaction of N -(trifluoroacetyl)glycylglycine methyl ester ( 44f ) carried out using visible light, biacetyl, and di- tert -butyl peroxide, in place of ultraviolet light and acetone, gave a 1:1 mixture of the phenylalanine derivatives 44g and 45g . The obvious difference between these reactions is the nature of the hydrogen atom-abstracting species, but it is not clear why that leads to a change in the ratio of products.…”

Nitrate esters in the generation of amino acid radicals

“…Studies of hydrogen atom transfer reactions of amino acid derivatives have shown them to be selective for reaction of glycine residues. [2][3][4][5][6] The reactions are also affected by the nature of the protecting groups applied to the amino and carboxy substituents, 7 and by polar and steric effects. 8 While these effects can be exploited in the regioselective functionalisation of amino acid and peptide derivatives, 3-7 the extent of regiocontrol is limited.…”

Recent Developments in the Use of N-Phthaloyl-Amino Acid Derivatives in Synthesis

“…An attempt to selectively brominate Nbenzoylvaline methyl ester in the presence of the corresponding glycine derivative resulted in preferential reaction of the glycine derivative. 17,18 A similar selectivity for reaction of glycine derivatives had been observed previously in biochemical systems 19 and through EPR studies of reactions of peptides and proteins, 20 and it had been exploited by Elad et al, [21][22][23][24][25] in the selective free radical alkylation of glycine residues in peptides and proteins. Reactions of this type occur without racemisation of other amino acid residues, which can therefore act as chiral auxiliaries in the production of the new chiral centre at the αcarbon of the glycine residue (Scheme 1).…”