From Unsaturated Amino Acids

In a multistep reaction sequence, A-Boc-L-allylglycine was converted into detoxinine 9 (84TL4133). Hydroxymethyl L-allylglycine was converted via a lactone into (-)-bulgenicine 10 (86TL6079). 

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In addition to resolution approaches, there are three main methods to prepare amino acids by biological methods addition of ammonia to an unsaturated carboxylic acid the conversion of an a-keto acid to an amino acid by transamination from another amino acid, and the reductive animation of an a-keto acid. These approaches are discussed in Chapter 19 and will not be discussed here to avoid duplication. The use of a lyase to prepare L-aspartic acid is included in this chapter as is the use of decarboxylases to access D-glutamic acid. 

Najera and coworkers introduced a new class of cyclic alanine templates (227, equation 59), the structure of which was anchored on Schollkopf s bislactim ether . Palladium-catalyzed allylations of the chiral pyrazinone derivative 227 with allylic carbonates (228) as substrates led to the formation of y,i5-unsaturated amino acids (229a-c) under very mild and neutral reaction conditions, whereas the required base for enolate preparation has been generated in situ from the allylic carbonate during jr-allyl complex formation. With this protocol in hand, the alkylated pyrazinones 229 were obtained with excellent regio- and diastereoselectivities (>98% ds). Finally, hydrolysis with 6 N aqueous HCl under relatively drastic conditions (150 °C) led to the free amino acids. 

Other reactions are also possible. For example, R-H type compounds may be generated, and this is characteristic mainly for the aromatic amino acids. Smaller molecules, some unsaturated, are also formed by further decompositions. The compounds of the type R-CH=N-CH2-R and R-C=N-CH2-R are formed mainly from aliphatic amino acids (Ala, Val, Leu, lie). 

Noyori asymmetric hydrogenation Formation of enantio-enriched carboxylic acids, alcohols and amino acids from unsaturated carboxylic acids, allylic alcohols and enamides, respectively. 316... 

In addition to carbon-based radicals, other radicals such as sulfur-based radicals, generated from an RSH-type precursor (R = alkyl, acyl) with AIBN also smoothly added to allylglycine.4 Optimal results were obtained when both the unsaturated amino acids and RSH dissolved completely in the reaction medium (dioxane-water or methanol-water were found to be superior solvents). Radical additions of thiophenol to carbon-carbon multiple bonds and radical cyclisation of A-allyl-2-iodoalkanamide in aqueous media proceeded smoothly to the A-acetylpyrrolidine derivative in 96% yield. Under similar... 

Of particular synthetic importance are the subsequent transformations of the initially formed adducts (103) and analogs thereof. For example, hydrolysis of (106) provides the 3-hydroxy-a-amino acid ester (107) together with Val-OMe (Scheme 43). On the other hand, dehydration of (108) with thionyl chloride in the presence of 2,6-lutidine furnishes a mixture (4 1) of (109) and (110) hydrolysis of the former led to the unsaturated amino acid (111 Scheme 44). a-Alkenylglycine methyl esters may be also prepared from the silyl derivatives (112 Scheme 45). An alternative route to a-alkenylglycines features the addition of the metallated derivative of (101) to thioketones followed by S-methylation to provide adducts (113), which undergo elimination of methanethiol upon reaction with Raney nickel (Scheme 46). ... 

Lewis acid catalyzed ene reactions of ethyl glyoxylate with allylglycine derivatives have been described as a route to highly functionalized unsaturated amino acids. SnCU-cataiyzed ene reactions of phenylglyoxal with alkenes occur in 40-78% yield. Treatment of the adducts obtained from monosub-stituted alkenes with periodate gives 3-alkenals in 50-70% yield. °... 

One problem of prime importance is the reliable determination of the number of residues of ,/3-unsaturated amino acids in proteins. Direct amino acid analysis subsequent to total hydrolysis of proteins is not feasible. The ,/3-unsaturated amino acids are subject to degradation with the formation of amide (ammonia) and -keto-acid. The numbers and types of ,/3-unsaturated amino acids in nisin (1) and subtilin (10) and in the fragments of the two peptides were, nevertheless, determined by amino acid analysis, only, however, after the addition of mercaptan across the double bonds of dehydroalanine and dehydrobutyrine (19). Using benzylmercaptan, the addition products are S-benzylcysteine (from dehydroalanine) and /3-methyl-S-benzylcysteine (from dehydrobutyrine). The two thioether amino acids are eluted from ion exchange columns of the amino acid analyzer free from interference by other amino acids... 

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