3- -aminoacrylate, formation

While investigating the biomimetic formation of cysteine, Schmidt et al. 2331 added thiolates to N-protected chiral a-aminoacrylic acid derivatives (dehydropeptides). (235) was obtained in optical yields up to 90 %. 

Fig. 7.9 Mechanism of formation of tautomeric quinonoid intermediates in the synthesis of L-tryptophan. The conversion of ES III (see also Fig. 7.6) to ES IVA is probably catalyzed by B2 which abstracts the proton on N-l of the heterocyclic ring concomitant with attack of indole on the aminoacrylate. The tautomerization of ES IVA to yield ES IVB is carried out by abstraction of the proton at C3 of indole by a basic group, Bi, concomitant with protonation of N-l by B2H (modified from Ref. 6).

Elimination of indole from the second quinonoid intermediate (Fig. 9.13, IV) results in formation of the aminoacrylate Schiff base intermediate (Fig. 9.13, V). The latter may either decompose to the final products completing the reaction of a, -elimination or may add a new reactive group (R-H, where R is a -SH, -SCH3, -OH, or -OCH3 group) at... 

P-Elimination and then replacement reaction of an a-amino acid with a nucleophile is very attractive from the viewpoint of synthetic organic chemistry because various P-substituted alanines may be prepared from a simple a-amino acid, such as serine, and nucleophiles. A reaction catalyzed by tryptophan synthase - the formation of tryptophan from serine and indole - is one of the most well-known P-elimination and replacement reactions (Scheme 2.7). Here, an aldimine Schiff base is derived from reaction of the enzyme-bound PLP with serine, which then dehydrates to give the Schiff base of PLP with 2-aminoacrylate. Indole then adds to the vinyl Schiff base, generating tryptophan after lysine aminolysis of the Schiff base product. 

The a subunit catalyzes the formation of indole from indole-3-glycerol phosphate, whereas each P subunit has a PLP-containing active site that catalyzes the condensation of indole and serine to form tryptophan. The overall three-dimensional structure of this enzyme is distinct from that of aspartate aminotransferase and the other PLP enzymes already discussed. Serine forms a Schiff base with this PLP, which is then dehydrated to give the Schiffbase of aminoacrylate. This reactive intermediate is attacked by indole to give tryptophan. 

Amino acid 78 and its y-glutamyl derivative are other components of the major pool of seleno compounds in accumulator plants, while selenomethionine (79) is the major compound in microorganisms like yeast, which is not specialized in selenium utilization. Se-Methylselenocysteine 5e-oxide (80), which is found in marine algae, tends to spontaneously decompose with the formation of pyruvate and ammonia via aminoacrylic acid and methaneselenic acid (81). The latter reacts with sulfhydryls or selenols to selenodisulfldes and diselenides. 

Cook, P.F., Tai, C.H., Hwang, C.C., Woehl, E.U., Dunn, M.F., and Schnackerz, K.D. (1996) Substitution of pyridoxal 5 -phosphate in the O-acetylserine sulfhydrylase from Salmonella typhimurium by cofactor analogs provides a test of the mechanism proposed for formation of the alpha-aminoacrylate intermediate. J. Biol. Chem. 271, 25842-25849. 

Both the l- and D-serine deaminase catalyze the elimination of the amino functionality of both l- and D-serine, but the mechanism proceeds via the initial elimination of water and these enzymes are thus classified as hydrolyases (l- and D-serine dehydratases E.C. 4.2.1.13 and E.C. 4.2.1.14, respectively)[27, 28. The aminoacrylate generated is unstable and subsequent elimination of the amine results in the formation of pyruvate. Similarly, threonine deaminase is in effect a dehydratase that converts L-threonine into 2-oxobuturate, water and ammonia (E.C. 4.2.1.16) (Scheme 12.6-1). 

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