Z-AlANINE

In the synthesis of l,2,5-triazepine-l,5-diones, which are expected to mimic the structural features of or-peptidyl prolin-amides, the preparation of N2,N3-disubstituted derivatives 213a from the reaction of (Z)-alanine with the N2-substituted triazepines 213 resulted in lower yields. It has been reported that these fused triazepinediones could be elaborated to give constrained rir-peptidyl proline peptide mimetics of defined stereochemistry and sequence <1997J(P1)2297>. 

In other cases, the recognition sites accept structurally related molecules. Polymers imprinted with Z-L-phenylalanine (5a) were able to resolve racemic Z-phenylalanine efficiently (Table 17.3). Racemic Z-alanine (5b) could also be resolved on these CSPs, although lower separation factors were observed. When the amino group of the racemate was protected with Boc (/erf-butyloxycarbonyl)... 

RSSF spectroscopy has also been used to study the effect of active site mutations on the 3-elimination reaction catalyzed by tryptophanase. In many PLP-de-pendent enzymes, the Lys residue that forms the E(Ain) with the cofactor is preceded by a basic residue in the primary amino acid sequence. Phillips et al. (106) have examined the effect of changing Lys 269 to Arg on the formation and accumulation of reaction intermediates. The activity of the mutant enzyme is only 1096 of the native enzyme. Secondly, the mutant enzyme exhibits an altered pH dependence both in the spectrum of the native enzyme and in the catalytic rate profile. RSSF studies of the reaction of/.-alanine, z-Trp, S-methyl-z-cysteine, S-benzyl-z-cysteine (SBC), and oxindolyl-/-alanine show that all these various substrates react with the enzyme to form covalent intermediates. However, the rate and extent of quinonoid accumulation is greatly reduced. Analysis of quinonoid bands formed in the reactions of SBC and oxindolyl-z-alanine with tryptophanase show that mutation effects the equilibrium distribution of intermediates, but does not perturb either the band shape or the A x of the observed quinonoid intermediates. Therefore, the structure of the quinonoid intermediate and the surrounding active site environment are similar to the wild-type enzyme. SWSF characterization of these reactions show that the Keq for E(Aex) formation with each substrate is similar to that found for the wild-type enzyme. Instead, the primary effect of the Lys 269 Arg mutation is at the catalytic step in which the a-proton is removed from E(Aex) to form a quinonoid. These studies show that Lys 269 is not a critical catalytic residue nevertheless it does contribute to the conformational and/or electrostatic environment of the active site that is necessary for the formation and breakdown of quinonoidal species. 

Since its discovery in 1974, more than 180 papers have been published on the use of the Overmann rearrangement to prepare allylic amines and their analogs from their allylic alcohols. For example, a recent synthesis of the fluoroalkene peptidomimetic precursor of A -acetyl-Z,-glutamyI-Z.-alanine involves the Overman rearrangement of the imidate derived from the allylic alcohol 60. ° This alcohol is readily prepared through Evans asymmetric aldol reaction of oxozolidinone with an aldehyde. 

Thus, a reversal of the diastereoseleetivity of the reaetion was observed if the enolate was prepared in the presenee of a lithiated base. The different behaviour of the base could be attributable to the geometry of the enolate. It was assumed that the use of KOH as a base would give predominantly the E enolate, whereas the Z enolate would be formed with a lithiated base such as LiN(TMS)2- This methodology was applied to the asymmetric synthesis of quaternary a-amino acids starting from an imino alaninate compound. 

Ethyl (Z)-A/-benzyl-A/- [methyl(1-methylthioethylidene-aminooxycarbonyl)amino]thio -/3-alaninate... 

The process was also applicable to microwave-assisted reactions. Thus, 140a, 140b, and 140 (R1 = z-Pr, R4 = indol-3-ylmethyl) were prepared in a two-step, one-pot synthesis in yields of 55%, 39%, 20%, and with 70%, 73%, 50% ee, respectively. In the first step anthranilic acid was reacted with the appropriate A-BOC-protected amino acid (glycine, L-alanine, and L-valine, respectively) in the presence of P(OPh)3 and dry pyridine under irradiation at 150 °C for 140a or conventional heating at 55 °C for 140b and 140 (R1 = z-Pr, R4 = indol-3-ylmethyl). In the second step the resulting... 

The behavior of 2-alkylthiohydantoins 428 and 3-chlorobenzopyrano[2,3-c]pyrazole 430 toward er-amino acid derivatives was studied. 2-Alkylthiohydantoins 428 condensed with alanine at high temperature, and the reaction of 3-chlorobenzopyrano[2,3-z]pyrazole 430 with ethyl glycinate was carried out in DMF at reflux to give the cycloadduct 431 in 62% yield (Equations 197 and 198) <2000PS77, 2000FA641>. 

Hu Z, Guan W, Wang W, Huang L, Xing H, Zhu Z (2007a) Synthesis of [1-alanine C60 derivative and its protective effect on hydrogen peroxide-induced apoptosis in rat pheochromocytoma cells. Cell Biol Int. 31 798-804. 

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