Dehydroalanine derivatives

Formation of the very unstable dehydroalanine derivatives A p-dimethylaminophe-nyl- and Af-p-nitrophenyhnethylenedehydroalanine methyl ester could only be verified by -NMR. Because of Michael-type reactions with cuprates, the iV-arylmethylenedehy-droalanine methyl esters have been applied as building blocks in the synthesis of amino acids.[18]... 

Addition of diazoraethane to a dehydroalanine derivative gave a reduced pyrazole which afforded pyrazole-3-carboxylic acid in the presence of HCl (83TL2193). 

The synthesis of lanthionines via dehydroalanines has been carried out using an (9,5-di-benzoylated Z-L-Cys-L-Ser-OMe. 31 Using (3-elimination under basic conditions in sodium methoxide and subsequent intramolecular Michael addition, the corresponding L-lanthio-nine derivative was formed. However, as a final step the cyclolanthionyl dipeptide would have to be cleaved at the amide bond to obtain lanthionine. The same authors reported the use of the O-tosylated serine dipeptide which was subjected to (3-elimination, forming the desired dehydroalanine derivative. However, this synthesis also yielded cyclic L-lanthionine dimers as a result of an intermolecular Michael addition. The amounts of cyclolanthionine and lanthionine dimer derivatives depended on the initial concentration of the dipeptides. In addition, the directed synthesis of cyclic lanthionine dimers, which were produced from N-benzyloxycarbonyl-W-trityllanthionine monomethyl ester, has been reported. 32 ... 

H. Kessler, V. Wittmann, M. Kock, and M. Kottenhahn, Synthesis of C-glycopeptides via radical addition of glycosyl bromides to dehydroalanine derivatives, Angew. Chem. Int. Ed. Engl. 3/ 902 (1992). 

The thiazepine 183 was easily obtained in a one-pot reaction of 182 with cysteamine-HCl and l,8-diazacyclo[5.4.0]-undec-7-ene (Equation 13) <1996JOC6060>. Monocyclic homochiral thiazepin-5-ones were prepared from a 1,3-diol and protected cysteine <20020L1235> or from penicillamine and dehydroalanine derivatives <1997LA17110>. 

Anomeric thioglycoslydes reacted with tripeptides containing dehydroalanine, derived from selenocysteine by oxidative elimination, thus affording S-linked neoglycopeptides through chemoselective Michael addition (Fig. 28e).116... 

Losse et al. have demonstrated that the difficulty in the hydrogenolytic debenzylation of S-protected cysteine derivatives is due to the strong poisoning action of thiols that may be formed probably by a P elimination of the cysteine to give the dehydroalanine derivative.83 The overall reaction in the case of Z-Cys(Bzl)-OBzl may be formulated as in eq. 13.43. 

The pair of unshared electrons on the carbanion can undergo two reactions (a) it can recombine with a proton from the solvent to regenerate either the original amino acid side chain or its optical antipode, so that it is racemized (b) it can undergo the indicated 6-elimination reaction to form a dehydroalanine derivative, which can then combine with an e-amino group of a lysine side chain to form a lysinoalanine crosslink. 

Another conjugate addition, to the dehydroalanine derivative 38 on solid-phase, was reported by Yim et al. [19], Radical generation using t-butyl iodide and tribu-tyltin hydride afforded only 8% of the desired product, while better results were obtained with organomercurials (Scheme 8). The intermolecular addition of tosyl radicals to unactivated alkene and alkyne 39 has also been reported [20], and the reaction was found to be quite sensitive to solvent. Optimum results were obtained in toluene, although the scope is difficult to gauge with only two examples disclosed. 

As already mentioned, dehydroalanine is the postulated reactive precursor for lysinoalanine. Direct evidence for dehydroalanine reactivity was obtained by Friedman et al. (1977). They showed that dehydroalanine derivatives convert lysine side chains in casein, bovine serum albumin, lysozyme, wool, or polylysine to lysinoalanine residues at pH 9 to 10. Related studies showed that protein SH groups generated by reduction of disulfide bonds are completely alkylated at pH 7.6 to lanthionine side chains. These studies demonstrate that lysinoalanine and lanthionine residues can be introduced into a protein under relatively mild conditions, without strong alkaline treatment. They also imply that it should be possible to explore nutritional and toxicological consequences of lysinoalanine and lanthionine consumption in the absence of racemiza-tion (see below). 

Amino acids with appropriate 3-substituents have frequently been employed as a,p-dehydroamino acid precursors, particularly in the form of peptide chain subunits. Elimination reactions from derivatives of P-hydroxy- and P-mercapto-a-amino acids are the examples most often encountered. Of less importance are amino acid derivatives with P-halogen substituents (38, 132, 337, 386, 394, 395), as these require more drastic elimination conditions. Mannich bases of monoalkyl acylaminomalonates have also found use as precursors of dehydroalanine derivatives (177, 438). 

Sakakibara, S. Studies on Dehydroalanine Derivatives. IV. Synthesis of N-Phthaloyl-Dehydroalanine by Thermal Decomposition of Cysteine and Serine in the Presence of Phthalic Anhydride. Bull. Chem. Soc. Jap. 34, 171 (1961). 

Sokolovsky, M., M. Wilchek, and A. Patchornik The Formation of Dehydroalanine Derivatives from S-DNP Cysteine Peptides. Proc. 30th Meeting of the Israel Chem. Soc. IIA, 79 (1962). 

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