A-amino acid intermediate

C. Preparation of Quinoxalines Using a-Amino Acid Intermediates 210... 

C. Phepaeation of Quinoxalines Using a-AMiNO Acid Intermediates... 

The pharmaceutical industry has been giving increased attention to homogeneous asymmetric hydrogenation for the synthesis of chiral molecules due to significant improvements in this technology (1). We recendy synthesized a chiral a-amino acid intermediate using Et-DuPhos-Rh catalyst, obtaining enantiomeric pmities (EP) of... 

Oxidative deamination is stereospecific and is catalyzed by L- or D-amino acid oxidase. The initial step is removal of two hydrogen atoms by the flavin coenzyme, with formation of an unstable a-amino acid intermediate. This intermediate undergoes decomposition by addition of water and forms ammonium ion and the corresponding a-keto acid L-Amino acid oxidase occurs in the liver... 

In a modification of the original method. Read (60) replaced a-amino acids with a-amino nitriles. This reaction is sometimes known as Strecker hydantoin synthesis, the term referring to the reaction employed for the synthesis of the a-amino nitrile from an aldehyde or ketone. The cycli2ation intermediate (18) has been isolated in some cases (61), and is involved in a pH-controUed equiUbrium with the corresponding ureide. 

One particular type of polyamide produced from intermediates containing lateral side groups are the poly-(a-amino acids). The a-amino acids have the structure shown in Figure 18.23 (I) and give polymers of the type shown in Figure 18.23 (II). The proteins may be considered as a special class of such... 

Tnflrc anhydride is a useful reagent for the preparation of covalent triflate esters from alcohols, ketones, and other organic substrates [66] In many cases, very reactive triflates can be generated m situ and subjected to subsequent transformation without isolation [94, 95, 96, 97] Typical examples are cyclization of amides into dihydroisoqumolines (equation 45) and synthesis of Al-hydroxy-a-amino acid denvatives (equation 46) via the intermediate covalent triflates... 

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

Implication of the same type of intermediate (342 X = H) allows the rationaUzation of the acid-catalyzed decarboxylation of 1,2,3,4-tetrahydro-j8-carboline-l-carboxylic acids. As is stated in Section III,A,1, a, the tetrahydroisoquinoline-1-carboxylic acids and a-amino acids of analogous structure are converted into the corresponding... 

Asymmetric synthesis of a,a-disubstituted a-amino acids via an intramolecular Strecker synthesis using l,4-oxazin-3-one derivatives as key intermediates 97YGK982. 

Azlactones like 6 are mainly used as intermediates in the synthesis of a-amino acids and a-keto acids. The Erlenmeyer-Pldchl reaction takes place under milder conditions than the Perkin reaction. 

An a-amino acid 3 can be prepared by treating aldehyde 1 with ammonia and hydrogen cyanide and a subsequent hydrolysis of the intermediate a-amino nitrile 2. This so-called Strecker synthesis - is a special case of the Mannich reaction-, it has found application for the synthesis of a-amino acids on an industrial scale. The reaction also works with ketones to yield a, a -disubstituted a-amino acids. 

Yet a third method for the synthesis of a-amino acids is by reductive amination of an a-keto acid with ammonia and a reducing agent. Alanine, for instance, is prepared by treatment of pyruvic acid with ammonia in the presence of NaBH As described in Section 24.6, the reaction proceeds through formation of an intermediate imine that is then reduced. 

Step 1 of Figure 29.14 Transimination The first step in transamination is trans-imination—the reaction of the PLP—enzyme imine with an a-amino acid to give a PLP—amino acid imine plus expelled enzyme as the leaving group. The reaction occurs by nucleophilic addition of the amino acid -NH2 group to the C=N bond of the PLP imine, much as an amine adds to the C=0 bond of a ketone or aldehyde in a nucleophilic addition reaction (Section 19.8). The pro-tonated diamine intermediate undergoes a proton transfer and expels the lysine amino group in the enzyme to complete the step. 

The following compound is an intermediate in the biosynthesis of one of the twenty common a-amino acids. Which one is it likely to be, and what kind of chemical change must take place to complete the biosynthesis ... 

This procedure offers a reproducible method for the preparation of 2-phenyl-5-oxazolone, which is not commercially available It illustrates that strict attention to detail often smooths out an erratic procedure 2-Phenyl-5-oxazolone is, of course, an important intermediate in the synthesis of a-amino acids and related materials6... 

As has been outlined for the Strecker synthesis, the Ugi reaction also proceeds via initial formation of a Schiff base from an aldehyde and an amine. The imine intermediate is attacked by the isocyanidc, a process which is supported by protonation of the imine by the carboxylic acid component. The resulting a-amino nitrilium intermediate is immediately trapped by the carboxylate to give an 6>-acyl imidiate. All steps up to this stage are reversible. Only the final oxygen to nitrogen acyl shift is irreversible and delivers the A-acyl-a-amino amide as the thermodynamically favored product which contains two amide groups. 

The mechanistic analogy to the Streckcr synthesis becomes obvious in the addition of the isocyanide to the imine to produce the a-amino nitrilium intermediate. Since all four components are involved in this step, it might be expected that every chiral component (chiral groups R1, R2, R3, R4) contributes to diastereofacial differentiation in the nucleophilic attack on the imine. However, in peptide syntheses by four-component condensation5, the chiral isocyanide or a chiral carboxylic acid component has only limited influence on the diastereoselectivity of the a-amino amide formation5. 

The title compound is a key C6 building block. Several labs have prepared novel a-amino acids, biological probes and other interesting compounds using the D-diepoxide as a key intermediate.3 An efficient route to the L-enantiomer provides a pathway to compounds with the opposite configuration, one not readily available from commercial sources, and a valuable probe of stereochemistry in biological systems and reaction mechanism. 

The synthesis of a-amino acids by reaction of aldehydes or ketones with ammonia and hydrogen cyanide followed by hydrolysis of the resulting a-aminonitrile is called the Strecker synthesis. Enzymatic hydrolysis has been applied to the kinetic resolution of intermediate a-aminonitriles [90,91]. The hydrolysis of (rac)-phenylglycine nitrile... 

Optically pure a-amino acids can be converted to 1,2-diamines by a route that involves the preliminary formation of N-protected a-aminonitriles through the intermediate amides. The addition of organometallic reagents to these a-aminonitriles gives a-amino ketimines, which are then reduced in situ to 1,2-diamines. However, this route has been scarcely applied to acychc a-aminonitriles. As a matter of fact, the sequential addition of methylmag-... 

In many cases, the racemization of a substrate required for DKR is difficult As an example, the production of optically pure cc-amino acids, which are used as intermediates for pharmaceuticals, cosmetics, and as chiral synfhons in organic chemistry [31], may be discussed. One of the important methods of the synthesis of amino acids is the hydrolysis of the appropriate hydantoins. Racemic 5-substituted hydantoins 15 are easily available from aldehydes using a commonly known synthetic procedure (Scheme 5.10) [32]. In the next step, they are enantioselectively hydrolyzed by d- or L-specific hydantoinase and the resulting N-carbamoyl amino acids 16 are hydrolyzed to optically pure a-amino acid 17 by other enzymes, namely, L- or D-specific carbamoylase. This process was introduced in the 1970s for the production of L-amino acids 17 [33]. For many substrates, the racemization process is too slow and in order to increase its rate enzymes called racemases are used. In processes the three enzymes, racemase, hydantoinase, and carbamoylase, can be used simultaneously this enables the production of a-amino acids without isolation of intermediates and increases the yield and productivity. Unfortunately, the commercial application of this process is limited because it is based on L-selective hydantoin-hydrolyzing enzymes [34, 35]. For production of D-amino acid the enzymes of opposite stereoselectivity are required. A recent study indicates that the inversion of enantioselectivity of hydantoinase, the key enzyme in the... 

Figure 30-11. Intermediates in i-hydroxyproline catabolism. (a-KA, a-keto acid a-AA, a-amino acid.) Numerals identify sites of metabolic defects in hyperhydroxyprolinemia and type II hyperprolinemia.

It can also be done by in situ generation of other types of electrophiles. For example, good yields of /V-acyl a-amino acids are formed in a process in which an amide and aldehyde combine to generate a carbinolamide and, presumably, an acyliminium ion. The organopalladium intermediate is then carbonylated prior to reaction with water.254... 

Petasis reported an efficient addition of vinyl boronic acid to iminium salts.92 While no reaction was observed when acetonitrile was used as solvent, the reaction went smoothly in water to give allyl amines (Eq. 11.54). The reaction of the boron reagent with iminium ions generated from glyoxylic acid and amines affords novel a-amino acids (Eq. 11.55). Carboalumination of alkynes in the presence of catalytic Cp2ZrCl2 and H2O affords vinylalane intermediates, which serve as nucleophiles in the subsequent addition to enantiomerically enriched... 

The removal of a carbobenzyloxy group can be separated into two steps (Figure 1). The first step comprises the hydrogenolysis of the benzyl oxygen bond of the Cbz-protected amino acid 1 to form a carbamic acid intermediate 2 and toluene 3. The carbamic acid intermediate decaiboxylates to give the deprotected amino acid 4 and one equivalent of carbon dioxide 5. 

In 2001, Linder and Podlech studied the microwave-assisted decomposition of diazoketones derived from a-amino acids [340]. In the presence of imines, the initially formed ketene intermediates reacted spontaneously by [2+2] cydoaddition to form /3-lactams with a trans substitution pattern at positions C-3 and C-4 (Scheme 6.179) [340], In order to avoid the use of the high-boiling solvent 1,2-dichlorobenzene, most transformations were carried out in 1,2-dimethoxyethane under sealed-vessel conditions. Solvent-free protocols, in which the substrates were adsorbed onto an inorganic alumina support, led only to the corresponding homologated /3-amino acids. Evidently, traces of water present on the support trapped the intermediate ketene. 

A method for the preparation of 1,3,2-diazaphospholidine heterocydes has been described by Deng and Chen (Scheme 6.225) [402], The authors found that treating hindered 1,2-diamino substrates such as a-amino acid amides with tris(diethylami-no)phosphine as reagent/solvent under open-vessel microwave conditions at 250 °C for 1 min furnished a trivalent phosphorus intermediate. Subsequent thiation of this intermediate with elemental sulfur in refluxing benzene provided the target l,3,2-diazaphospholidin-4-ones in good overall yields. The yields were much improved compared to those achieved by standard thermal methods. 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

DIPAMP-Rh complex to give the corresponding chiral a-amino acid derivative in over 98% ee. The chiral product has been used for the synthesis of (S)-(-)-ac-romelobic acid [88]. Hydrogenation of a tetrahydropyrazine derivative catalyzed by a PHANEPHOS-Rh complex at -40"C gives an intermediate for the synthesis of Crixivan in 86% ee [82a]. Hydrogenation of another tetrahydropyrazine carboxamide derivative catalyzed by an (R)-BINAP-Rh catalyst leads to the chiral product in 99% ee [89]. 

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