Yolande Hervé

Manipulation of the cabboxyl groups of α-amino-acids and peptides using radical chemistry based on esters of N-hydroxy-2-thiopyridone

Abstract Photolysis of α-amino-acid or peptide esters derived from N -hydroxy-2-thiopyridone in the presence of t -butylthiol affords the expected decarboxylation products in good yield. The reaction can be applied to the α-carboxyl or to the side chain carboxyl of glutamic and aspartic acids and thus permits the preparation of a number of useful synthons. Photolysis of side chain esters in the presence of a suitable halogen atom transfer reagent gives halides often in good yield and, especially in the case of aspartic acid derivatives, without racemisation.

The free radical chemistry of carboxylic esters of 2-selenopyridine-N-oxide: a convenient synthesis of (L)-vinylglycine

Abstract Optically pure (L)-vinylglycine has been synthesised by two different methods. The first of these involves protected (L)-glutamate esters of N -hydroxy-2-seleno-pyridine. Such esters are shown to undergo the same decarboxylotive rearrangement as their thio-analogues. Oxidative elimination of the selenopyridine residue with ozone, and with the aid of hex-1-ene as sacrificial olefin for the work-up, gave the desired (L)-vinylglycine derivatives. Similarly, the modified Hunsdiecker reaction on the terminal carboxyl of suitably protected (L)-glutamic derivatives gave the nor-bromide which readily afforded the corresponding phenylselenides on treatment with phenylselenide anion. The sequence was then as above. Using the methyl ester with corbobenzyloxy protection for the amino-function an overall yield of crystalline optically pure (L)-vinylglycine of about 45% was obtained by either route.

Synthesis of novel α-amino-acids and derivatives using radical chemistry: synthesis of L- and D-α-amino-adipic acids, L-α

Abstract Radicals generated by photolysis (W light) of suitably protected amino-acid derivatives of N -hydroxy-2-thiopyridone add efficiently to activated olefins to afford satisfactory yields of adducts. Oxidation of the thiopyridyl residue to sulphoxide and thermal elimination afford excellent yields of the corresponding α, β-unsaturated derivatives. Lateral chain decarboxylation of suitably protected aspartic and glutamic acids provides convenient syntheses of L-α- and D-α-aminoadipic acids, of L -α-aminopimelic acid and of L -α-amino-δ- trans -dehydropimelic acid.

Concise syntheses of L-selenomethionine and of L-selenocystine using radical chain reactions

Abstract L-Selenomethionine and L-selenocystine were prepared in high overall yields from protected L-glutamic and L-aospartic acid derivatives respectively. Irradiation of the mixed anhydrides (esters) derived from 4 (e.g. 15 ) in the presence of dimethyldiselenide provided the protected L-selenomethionine 16 directly. We have shown that triselenocyanide Se3(CN)2 can serve as an efficient selenocyanating agent for radicals; the selenocyanide group is a good precursor for the diselenide moiety of L-selenocystine.

Reductive radical decarboxylation of amino-acids and peptides

Radicals generated from N-protected α-amino-acids by photolysis of their N-hydroxypyridine-2-thione esters at room temperature are efficiently quenched by t-butyl thiol to give decarboxy-acids; comparable reactions have been carried out on the side chain carboxy groups of suitably protected aspartic and glutamic acids.

Synthesis of 2S, 3aS, 7aS- and of 2S, 3aR, 7aR-Perhydroindole-2-carboxylic acid derivatives from L-aspartic acid

Abstract Using carbon radicals generated by photolysis of N -hydroxy-2-thio-pyridone esters (mixed anhydrides) the chiral centre of L -aspartic acid has been easily incorporated into the perhydroindole structure of the title compounds.

Synthesis of benzyl (6S)-1,3-dichloro-4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxylic ester, a new conformationally constrained peptidomimetic derivative

We describe the synthesis of benzyl (6S)-1,3-dichloro-4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxylic ester, a new conformationally constrained peptidomimetic derivative. This compound is prepared in seven steps from (S)-pyroglutamic acid as starting material.