From alanine

Significant producers include Daiichi, Hoffmann-La Roche, Takeda, and several factories in mainland China. Takeda and Daiichi practice processes based on alanine by ethoxyoxazole (12), at least one Chinese producer from alanine by oxazole acid (13), and Roche from ketene via cyanooxazole (15). 

Show the steps involved in the synthesis of Ala-Leu from alanine and leucine using benzyloxycarbonyl and benzyl ester protecting groups and DCCI-promoted peptide bond formation. 

Problem 26.17 Write all five steps required for the synthesis of Leu-Ala from alanine and leucine. 

The compound has been made by the last route from alanIne,... 

Aminotransferase (transaminase) reactions form pymvate from alanine, oxaloacetate from aspartate, and a-ketoglutarate from glutamate. Because these reactions are reversible, the cycle also serves as a source of carbon skeletons for the synthesis of these amino acids. Other amino acids contribute to gluconeogenesis because their carbon skeletons give rise to citric acid cycle... 

Proteins form in a sequence of condensation reactions in which the amine end of one amino acid combines with the carboxyl end of another, eliminating a water molecule to create an amide linkage. The amide group that connects two amino acids is called a peptide linkage, and the resulting molecule is known as a peptide. When two amino acids are linked, the product is a dipeptide. A dipeptide formed from alanine and glycine is shown in Figure 13-33. 

Carbobenzoxyalanine (m.p. 114-115°) is obtained in 80-90 per cent yield from alanine and benzyl chloroformate by the same procedure. 

R from alanine, valine, phenylalanine, methionine, tryptophan, and glutamine... 

Chiral dialkyl amphiphiles [61] and [62], prepared from alanine and glutamic acid (Kunitake et al., 1979b), also form bilayer structures when dispersed in water. Chiral bilayers should be interesting because they provide... 

Glucose produced by GNG from alanine or lactate may then be recycled to the tissues, including the muscle which provided the initial alanine and lactate. 

The rate of reaction 29 is found to be sensitive to the configuration of the guest A, making p-CD a gas-phase chiral selector. Its enantioselectivity, defined by the measured ko/kL ratio, is as large as far kolkL is from unit. Table 12 indicates that the /3-CD increases from alanine kolk = 0.62) to valine kolkL = 0.32), leucine... 

In liver, aminotransferases ALT and AST can move the amino group from alanine arriving from muscle into aspartate, a direct donor of nitrogen into the urea cycle. 

Figure 9-1. Molecular interconversions in handling of ammonia. The major enzyme responsible for interconversion of glutamate and a-ketoglutarate is glutamate dehydrogenase. No free ammonia is ever present during direct transfer of amino groups from alanine or aspartate via transamination to produce glutamate. ALT, alanine aminotransferase AST, aspartate aminotransferase.

In fact, the first saturated pseudoxazolone reported, 4-methyl-2-(trifluoro-methyl)-5(2//)-oxazolone, was incorrectly assigned as the tautomeric 5(4//)-oxazolone and only later did nuclear magnetic resonance (NMR) smdies establish the correct structure. This compound was synthesized from alanine and trifluoro-acetic anhydride (TFFA). This methodology constitutes, under standard conditions, the most general procedure for the synthesis of 5(2//)-oxazolones. 

When carbonyl compounds are used as electrophiles reaction with 4-monosub-stituted-5(4//)-oxazolones affords substituted serines after subsequent hydrolytic ring opening of the initial aldol product. As an example, 4-methyl-2-phenyl-5(4//)-oxazolone 193, prepared from alanine, reacts with benzaldehyde in a base-catalyzed addition to give, after hydrolysis, a 3 1 mixture of threo- and... 

Optically pure or almost pure a-methyl a-amino acids (alanine derivatives) can be prepared by reacting 5-substituted 2,5-dihydro-3,6-dimethoxy-2-methylpyrazines 1, which are derived from alanine and various amino acids as the chiral auxiliary, with alkylating agents, followed by hydrolysis (see Table 2). 

Figure 5 shows the modeled structure for the a helix F interface in human 11(3-HSD-1, in which phenylalanine-188 and alanine-189 form an anchor. Alanine-189 is 3.5 A and 4.7 A from alanine-189 and alanine-185, respectively, on the other subunit. The phenylalanine-188 side chain is 3.2 A from glycine-192. There is a hydrogen bond between serine-185 and serine-196, which are 3.2 A apart. Alanine-185 is 4.7 A from phenylalanine-193. There also is a hydrophobic interaction between phenylalanine-193 and alanine-181, which are 3.9 A apart. 

Figure 6a shows the modeled oc helix F interface in human 17 3-hydroxysteroid dehydrogenase type 1 in which phenylalanine-160 and alanine-161 form an anchor. Both residues have important stabilizing interactions across the dimer interface. Alanine-161 is 4.1 A from alanine-161 on the other subunit. Alanine-161 has a hydrophobic interaction with alanine-157, which is in the segment between the conserved tyrosine-155 and lysine-159. There is a hydrophobic... 

Figure 6b shows the modeled a helix F interface in human 17P-hydroxysteroid dehydrogenase type 2. Alanine-237 is 3 A from the hydrophobic part of the side chain of methionine-241 on the other subunit. Methionine-241 is 3.2 A from serine-234. Alanine-230 is 3.7 A from phenylalanine-242 and 4.5 A from valine-245. Alanine-238, the other anchoring residue, is 4.1 A from alanine-238 on the other subunit. 

Figure 6d shows the modeled a helix F interface in pig 17 P-hydroxy steroid dehydrogenase type 4. Leucine-169 is 2.9 A from glycine-173. Leucine-174 is 4.3 A from alanine-162 and 3.3 A from alanine-166. There also is a hydrogen bond between serine-165 and serine-175, which are 3 A apart. 

Pyruvate is first transported from the cytosol into mitochondria or is generated from alanine within mitochondria by transamination, in which the a-amino group is removed from alanine (leaving pyruvate) and added to an a-keto carboxylic acid (transamination reactions are discussed in detail in Chapter 18). Then pyruvate carboxylase, a mitochondrial enzyme that requires the coenzyme biotin, converts the pyruvate to oxaloacetate (Fig. 14-17) ... 

Ammonia transport in the blood from the peripheral tissues to the liver occurs by two major mechanisms glutamine can be synthesized from glutamate and ammonia (glutamine synthetase) or pyruvate can be transaminated to alanine. In the liver, the ammonia group is removed from glutamine by glutaminase and from alanine by transamination. 

Experimental support for the mechanism of Eq. 15-26 has been obtained using D-chloroalanine as a substrate for D-amino acid oxidase.252-254 Chloro-pyruvate is the expected product, but under anaerobic conditions pyruvate was formed. Kinetic data obtained with a-2H and a-3H substrates suggested a common intermediate for formation of both pyruvate and chloro-pyruvate. This intermediate could be an anion formed by loss of H+ either from alanine or from a C-4a adduct. The anion could eliminate chloride ion as indicated by the dashed arrows in the following structure. This would lead to formation of pyruvate without reduction of the flavin. Alternatively, the electrons from the carbanion could flow into the flavin (green arrows), reducing it as in Eq. 15-26. A similar mechanism has been suggested for other flavoenzymes 249/255 Objections to the carbanion mechanism are the expected... 

Constructing a quaternary center by the alkylation of azlactones has led to development of a new strategy for the synthesis of sphingosine analogs. The azlactone derived from alanine was alkylated with a gem-diacetate to give a 10.5 1 mixture of diastereomers both with 89% ee [191 ]. 

The crystal structure of the N-terminal 80 residues of tropomyosin (Brown et al., 2001) contains its first alanine cluster and displays two specific consequences of this motif for the main-chain geometry of the coiled-coil. One is that the coiled-coil in this segment becomes locally narrow, to 8.0 A diameter, as would be expected from alanine s small size. This feature is directly related to the stability of the coiled-coil in a 10 A wide dimeric coiled-coil, a pair of core alanines from the opposite helices would generally leave unfilled spaces in the interior these spaces become smaller as the main chains of the helices approach each other and the core becomes more close-packed. Recent studies of model coiled-coils with identical amino acid compositions, but different arrangements,... 

This important flavor compound was identified in the head-space volatiles of beef broth by Brinkman, et al. (43) and although it has the odor of fresh onions, it is believed to contribute to the flavor of meat. This compound can be formed quite easily from Strecker degradation products. Schutte and Koenders (49) concluded that the most probable precursors for its formation were etha-nal, methanethiol and hydrogen sulfide. As shown in Figure 5, these immediate precursors are generated from alanine, methionine and cysteine in the presence of a Strecker degradation dicarbonyl compound such as pyruvaldehyde. These same precursors could also interact under similar conditions to give dimethyl disulfide and 3,5-dimethyl-l,2,4-trithiolane previously discussed. 

Two epimeric amino alcohols, 2(5)-aminotetradeca-5,7-dien-3(5)- and -3(/ )-ol (305 and 306) were isolated from a sponge from Papua New Guinea (Xestospongia sp.) (248). The absolute stereochemistry was disclosed by degradation to L-alanine, and these amino alcohols (305 and 306) were suggested to be biosynthesized from fatty acids and alanine. Compounds 305 and 306 show antimicrobial activity. Rhizochalin (307) was isolated from the Madagascan sponge Rhizochalina incrustata as an antimicrobial constituent (349). The biosynthetic pathway for 307 is unknown but is conventionally believed to be derived from alanine and a polyketide precursors). 

Figure 4. Two-dimensional heteronuclear multiple quantum coherence spectrum of a medium sample taken from a culture of HeLa cells which had been grown for 48 hours in the presence of 2 mM L[2-15N]glutamine. In this type of experiment the, 5N label (FI axis) is detected indirectly via spin-coupled protons (F2 axis). The peaks labeled in the contour plot arise from alanine (Ala), glutamate (Clu), glutamine (Gin), glycine (Gly), aspartate (Asp), and pyrollidone carboxylic acid (Pyr). From Street etal., 1993, with permission.

Figure 2.13. Conformational plot for glycine-aspartic acid. The allowable conformations are only slightly reduced compared to the plot in Figure 2.12 because the side chain length is increased in going from alanine to aspartic acid.

The mutarotation when an amino-acid component is changed from alanine to proline is illustrated in Figure 13. In the case of amino pyrrolidine, mutarotation occurs, whereas with N-isopropylpropylene diamine, no mutarotation is observed. The deuterium-incorporation velocity of the methine proton in heavy methanol (CH3OD) parallels the mutarotation velocity. 

In the mutarotation experiment of iminazoline from alanine and isopropylpropylenediamine, the recovered alanine residue racemized entirely in methanol solution. Why, then, can the iminazoline containing the optically retained amino acid residue be synthesized ... 

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