Boc-Ala-OH

Boc-Ala-OH

Rapid approach to 3,5-disubstituted 1,4-benzodiazepines via the photo-fries rearrangement of anilides.[Pubmed:17109551]

J Org Chem. 2006 Nov 24;71(24):9217-20.

Different anilides derived from carboxylic acids and substituted anilines have been submitted to the photochemically induced Fries rearrangement giving the corresponding o-amino phenones under conditions that are compatible with the presence of acid-labile groups (such as N-Boc or TBDMSO) on R1 and R3. These compounds, not easily obtained in other ways, are useful building blocks for the preparation of benzocondensated heterocycles. After coupling with N-Boc amino acids and TFA-mediated deprotection, the products cyclized to the corresponding 3,5-disubstituted 1,4-benzodiazepin-2-ones, privileged structures predominantly active in the central nervous system. The same results were obtained by coupling with N-Cbz-protected alpha-amino acids followed by microwave assisted hydrogenolysis. When the Fries rearrangement was carried out on the anilide derived from N-Boc-Ala-OH and the further coupling done with N-Cbz-(OMe)Asp-OH, the formed benzodiazepines could be inserted in a peptide chain for the preparation of conformationally constrained peptidomimetics.

Radical acylation of L-lysine derivatives and L-lysine-containing peptides by peroxynitrite-treated diacetyl and methylglyoxal.[Pubmed:24328571]

Free Radic Res. 2014 Mar;48(3):357-70.

Highly electrophilic alpha-dicarbonyls such as diacetyl, methylglyoxal, 3-deoxyglucosone, and4,5-dioxovaleric acid have been characterized as secondary catabolites that can aggregate proteins and form DNA nucleobase adducts in several human maladies, including Alzheimer's disease, rheumatoid arthritis, diabetes, sepsis, renal failure, and respiratory distress syndrome. In vitro, diacetyl and methylglyoxal have also been shown to rapidly add up the peroxynitrite anion (k2 ~ 10(4)-10(5) M(-1) s(-1)), a potent biological nucleophile, oxidant and nitrosating agent, followed by carbon chain cleavage to carboxylic acids via acetyl radical intermediate that can modify amino acids. In this study, we used the amino acid derivatives Ac-Lys-OMe and Z-Lys-OMe and synthesized the tetrapeptides H-KALA-OH, Ac-KALA-OH, and H-K(Boc)ALA-OH to reveal the preferential Lys amino group targeted by acyl radical generated by the alpha-dicarbonyl/peroxynitrite system. The pH profiles of the reactions are bell-shaped, peaking at approximately 7.5; hence, they are close to the pKa values of ONOOH and of the catalytic H2PO4(-) anion. RP-HPLC and ESI-MS analyses of reaction products confirmed (alpha)N- and ()N-acetylation of Lys by diacetyl as well as acetylation and formylation by methylglyoxal, with preference for the alpha-amino group. These data suggest the possibility of radical acylation of proteins in epigenetic processes, where enzymatic acetylation of these biomolecules is a well-documented event, recently reported to be as critical to the cell cycle as phosphorylation. Also noteworthy is the observed formylation of L-Lys containing peptides by methylglyoxal never reported to occur in amino acid residues of peptides and proteins.

Evaluation of carbodiimides using a competition method.[Pubmed:9230479]

J Pept Sci. 1997 Mar-Apr;3(2):141-4.

A competitive reaction of activated Boc-Ala-OH and Boc-Phe-OH with H-Leu-resin has been developed for assessing the relative efficiencies of different carbodiimides. This allowed a comparison of the efficiency of the carbodiimides N,N'-dicyclohexylcarbodiimide,N,N'-diisopropylcarbodiimide, N-tert-butyl-N'-methylcarbodiimide and N-tert-butyl-N'-ethylcarbodiimide. Comparable results were obtained when these reagents were used for the preformation of symmetrical anhydrides or of 1-hydroxybenzotriazole esters in situ. Differential incorporation was observed when asymmetrical carbodiimides were used for peptide bond formation by the direct carbodiimide procedure.