Alanine laboratory synthesis

From the chemical equations above it is clear that the laboratory synthesis is not a clean reaction, because it yields a mixture of the both enantiomers L-alanine and D-alanin i.e. a racemate. The appearance of the racemate can be explained from the knowledge of the reaction mechanism of nucleophilic addition to the carbonyl group. In the carbonyl group the carbon atom is bound by a double bond and lies with all three of its substituents in the same molecular plane. The CN" group as a nucleophile can attack the carbonyl carbon with the same probability from either side of the molecular plane. Consequently above-the-plane attack yields (R) enantiomer and below-the-plane attack gives the (S) enantiomer. 

Keefe et al. (1995) from Stanley Miller s laboratory reported a possible prebiotic synthesis of pantetheine, the part of the CoA molecule without its ADP moiety. They were able to synthesize the CoA precursor from P-alanine, pantoyllactone and cysteamine. This condensation requires concentration of the reaction mixture the warm lagoon theory is required here in order to achieve prebiotic conditions ... 

There are several laboratory-size methods for synthesizing amino acids, but few of these have been scaled up for industrial production. Glycine and m.-alanine are made by the Stnecker synthesis, commencing with formaldehyde and acetaldehyde, respectively. In tile Strecker synthesis, aldehydes react with hydrogen cyanide and excess ammonia to give amino niiriles which, in turn, are converted into a -amino adds upon hydrolysis. 

The process of racemization has a number of practical application in the laboratory and in industry. Thus, in the synthesis of an optical isomer it is frequently possible to racemize the unwanted isomer and to separate additional quantities of the desired isomer. By repeating this process a number of times it is theoretically possible to approach a 100% yield of Synthetic product consisting of only one optical isomer, An example of the utilization of such a process is found in the production of pantothenic acid and its salts, In this process the mixture of D- and L-2-hydroxy-3,3-butyrolactones are separated. The D-lactone is condensed with the salt of beta-alanine to give the biologically active salt of pantothenic acid, The remaining L-lactone is racemized and recycled. 

Synthesis of polypeptides in the laboratory is much more complicated than the synthesis of the polyamides described in Chapter 24 because more than one monomer must be used and the order of their attachment must be carefully controHed. For example, suppose we want to prepare the dipeptide Gly-Ala. We cannot just heat a mixture of glycine and alanine. Although this would produce some of the desired dipeptide, it would also form a host of other products, including other dipeptides and tripeptides, as shown in the following equation ... 

The first known synthesis of an amino acid occurred in 1850 in the laboratory of Adolph Strecker in Tubingen, Germany. Strecker added acetaldehyde to an aqueous solution of ammonia and HCN. The product was a-amino propionitrile, which Strecker hydrolyzed to racemic alanine. 

We ll see in Chapter 29 that living organisms use many of the same tions that chemists use in the laboratory. This is particularly true of i bonyl-group reactions, where nucleophilic addition steps play a critical ruie in the biological synthesis of many vital molecules. For example, one of the pathways by which amino acids are made involves nucleophilic addition of an amine to w-keto acids. To choo.se a specific example, the bacterium Bari/ lus subtilis synthesizes the amino acid alanine from pyruvic acid. 

A new strategy for the synthesis of heterocyclic a-amino acids utilizing the Hantzsch dihydropyridine synthesis was developed in the laboratory of A. Dondoni." ° The enantiopure oxazolidinyl keto ester was condensed with benzaldehyde and fert-butyl amino crotonate in the presence of molecular sieves in 2-methyl-2-propanol to give a 85% yield of diastereomeric 1,4-dihydropyridines. The acetonide protecting group was removed and the resulting amino alcohol was oxidized to the target 2-pyridyl a-alanine derivative. 

The total synthesis of the marine-derived diterpenoid sarcodictyin A was accomplished in the laboratory of K.C. Nicolaou. The most challenging part of the synthesis was the construction of the tricyclic core, which contains a 10-membered ring. This macrocycle was obtained by the intramolecular 1,2-addition of an acetylide anion to an a, 3-unsaturated aldehyde. This unsaturated aldehyde moiety was installed by utilizing the Knoevenagel condensation catalyzed by (3-alanine. The Knoevenagel product was exclusively the ( )-cyanoester. 

Kynurenine. a,2-Diamino 7 OXobenzenebutanoic acid 3-a nth rani] oy] alanine. CIDHl2N,0, mol wt 208.21. C 57.68%, H 5.81%, N 13.46%. O 23.05%. An amino acid produced in ihe body frnm tryptophan, lsoln from urine o[ rabbits that had been fed tryptophan Matsuoka, Yoshimat-su, Z. Physio/. Chem. 143, 206 (1925) Butenandl et ai, ibid. 279, 27 (1943) Heidelberger el al, J. Biol, Chem, 179, 143 (1949). Structure and synthesis Butenandt et at., loc. cit. Laboratory prepn hy oxidation of L-iryptophan with a Pseudomonas sp. Hayaishi, Meister, Biochem. Prepn. 3, 108... 

It is possible to make amino acids quite straightforwardly in the laboratory. The scheme below shows a synthesis of alanine, for example. It is a version of the Strecker synthesis you met in Chapter 11. 

Alpha-bromination of a carboxylic acid is a critical step in some laboratory syndieses of amino acids. Devise a synthesis of racemic alanine from propionic acid. 

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