Substitution reactions, amino acid

Substituted derivatives of l-(tetrahydrobenzo[b]thiophen-2-yl-3-carboxylate)-5-phenyl-6-thio-l,2,4-triazin-4-one have been synthesized by heterocyclization reactions of different hydrazones obtained from 2-amino-tetrahydrobenzo[b]thiophene-3-carboxylate with phenyl isothiocyanate <00PS275>. Reaction of 5-methyl isothiosemicarbazide with a-amino acid vicinal tricarbonyl reactive substrates 1 and 2 yields 1,2,4-triazine substituted a-amino acids, as an equimolar mixture of regioisomers 3a/3b and 4a /4b, respectively <00JCS(P1)299>. 

Enantioselective synthesis of /1-amino acids is important as they are present in various natural products and in many biologically active compounds [26,27]. Several methods exist for the enantioselective synthesis of -substituted /1-amino acids (/l3-amino acids) however, synthesis of a-substituted /1-amino acids (/l2-amino acids) is very limited [28,29]. A report on highly enantioselective hydrogen atom transfer reactions to synthesize /l2-amino acids (Scheme 9) has recently been described [30]. 

We have also used mutagenic primers to insert histidine tags and epitope tags into cDNAs of interest (Neish et al, 2003). Inserting several codons into a cDNA is a little more difficult than simply substituting one amino acid for another, but is quite feasible using this technique. Optimization of the reaction is absolutely critical when performing more difficult manipulations such as this. 

Nohira et al. treated N-acylamino acids 195 with thionyl chloride mixed anhydrides 196 were formed below 30°C. The latter compounds gave the first type of hexahydro-2//-3,l-benzoxazin-4-one 197 on triethylamine treatment [77H(7)301]. This reaction was also performed with diexo- and diendo-substituted j8-amino acids 198 yielded the 5,8-methano-2//-3,l-benzoxazin-4-ones 199 via the acyl derivatives 200 (84S345,84T2385). Further homologs were also prepared by the dehydration of N-acylamino acid derivatives (85MI1 88MI3). 

Mesoionic oxazolones (munchnones) 297 can be generated by cyclodehydration of N-substituted a-amino acids 295 or by alkylation of oxazolones 296 (Scheme 7.98). These compounds are reactive and versatile 1,3-dipoles that undergo cycloaddition reactions with dipolarophiles to generate a variety of heterocyclic systems. In particular, this is an extremely versatile methodology to prepare pyrroles that result from elimination of carbon dioxide from the initial cycloadduct. Numerous examples have appeared in the literature in recent years and several have been selected for discussion. The reader should consult Part A, Chapter 4 for an extensive discussion and additional examples. 

Takemoto and his co-workers developed asymmetric allylic alkylation of allylic phosphates with (diphenyl-iminolglycinates as carbon-centered nucleophiles (Equation (56))/" " In this reaction system, use of optically active bidentate phosphites 142 bearing an (ethylthio)ethyl group as chiral ligands promotes the allylic alkylation, and chiral /3-substituted a-amino acids are obtained with an excellent enantioslectivity. 

The resulting product is, however, an N-substituted oxazolidine amino acid, but this can easily be removed by either reductive or oxidative (Fig. 7) procedures. These and similar reactions can be used to prepare y-hydroxy-a-amino acids, arylglycines, a-alkyl-a-amino acids, and a variety of nonproteinogenic dipeptides (Fig. 7). The review by Muzart (58) is an excellent source of further information on the use of Cr compounds in organic synthesis. 

A wide variety of a-tnfluoromethyl ab-ammo acids ate readily available from the reaction of 5-fluoro-4-tnfluoromethyl-l,3 azoles with allyhc alcohols [755, 759] a-Tnfluoromethyl-substituted a-amino acids show antibacterial and antihy pertensive activity Some are highly specific enzyme inhibitors (suicide inhibitors) and may be important as bioregulators [740] Furthermore, they are interesting candidates for peptide modification... 

The best substrates for ophidian L-amino acid oxidases are aromatic or, most generally, hydrophobic amino acids, polar and basic amino acids being deami-nated at much lower rates Glu, Asp, and Pro are not oxidized by L-amino add oxidase. L-Amino add oxidase is also active on ring-substituted aromatic amino acids, as well as on seleno cysteinyl derivatives. The substrate specificity depends on the source of the enzyme (e.g. Ophiophagus hannah L-amino acid oxidase also oxidizes Lys and Om) and on the pH. The of the reaction of Crotalus adaman-... 

The Ir-catalyzed enantioselective allylic substitution reaction can be used for the synthesis of -substituted a-amino acids . For example, the enantioselective Ir-catalyzed allylic substitution of 3-arylallyl diethyl phosphates 5.24 with pronucleophile diphenylimino gly-cinate 5.25 is achieved up to 98% ee by using bidentate chiral phosphite ligand 5.26. By changing the base, both diastereoisomeric substitution products 5.27a and 5.27b could be formed selectively. 

Addition of optically active 1-phenylethylhydroxylamines to a,/ -unsaturated esters proceeds in good yield but with modest diastereoselectivity for the isolated substituted /J-amino acid esters12. Thus, reaction of (S)-l-phenylethylhydroxylamine with methyl 2-methylpropenoate in diethyl ether affords the corresponding conjugate-adduct in 86% yield12. This is subsequent-... 

Preparation of Enantiopure a-Substituted p-Amino Acids. In preliminary studies, racemic 2-rerr-hutyl-perhydropyrimidinone, rac-4, was alkylated with high di-astereoselectivity via its corresponding enolate (eq 5). The high stereoselectivity encountered in the reaction of rac-4-Li with various electrophiles was ascribed to steric hindrance generated by the axial disposition of the tert-butyl group at C(2), which directs approach to the electrophile from the enolate face opposite to this group. 

In principle, a-substituted p-amino acids of opposite configuration, (S)-9-12, can be obtained when enantiomeric pyrimidinone (/ )-4 [from (/ )-asparagine] is used as the starting material, following the reaction sequence described above. Nevertheless, a practical alternative consisted in the epimerization of trani-adducts 5-8 to afford the cii-diastereoisomers 13-16 (eq 8). Hydrolysis of cw-13-16 provided the desired (5)-a-substituted p-amino acids, (5)-17-20 (eq 9) ... 

Total synthesis of natural products containing x-substituted x-amino acid structures from aldohexoses using Overman rearrangement as the key reaction 04YGK693. 

More specific flavors have been obtained by substituting specific amino acids and specific sugars. An example is the microwave reaction of Glucose, Phenylalanine and Leucine by Byrne and Buckholz to get a chocolate tasting flavor. 

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