Alanine preparation

Scheme 46 Cleavage of Peptides Containing Nucleo Alanines Prepared on MBHA Resin 83 ...

Harada and Matsumoto studied the effect of solvents on the % ee of the amino acids formed in asymmetric transamination.56 Generally, the optical activity of alanine prepared from benzyl pyruvate and (S )-)-)-1-phenylethylamine decreased with increasing polarity of the solvents used. From the finding that sodium a-phenylglycinate was hydrogenolyzed easily to ammonia and phenylacetate over palladium catalyst, Harada prepared optically active alanine, butyrine, glutamic acid, and aspartic acid in 40-60% optical purities from the corresponding a-oxo... 

Kokufuta, E., Terada, T., Suzuki, S. and Harada, K., 1978. Potentiometric titration behavior of a copolymer of glutamic acid and alanine prepared by thermal polycondensation. BioSystems, 10 299—306. 

For assembly of novel three-dimensional (3D) structures, block copolypeptides are required that have structural domains (i.e., amino acid sequences) whose size and composition can be precisely adjusted. Such materials have proven elusive using conventional techniques. Strong base-initiated NCA polymerizations are very fast. These polymerizations are poorly understood and well-defined block copolymers cannot be prepared. Primary amine-initiated NCA polymerizations are also not free of side reactions. Even after fractionation of the crude preparations, the resulting polypeptides are relatively ill-defined, which may complicate unequivocal evaluation of their properties and potential applications. Nevertheless, there are many reports on the preparation of block copolypeptides using conventional primary amine initiators. Examples include many hydrophilic-hydrophobic and hydrophilic-hydrophobic-hydrophilic di- and triblock copolypeptides (where hydrophilic residues were glutamate and lysine, and hydrophobic residues were leucine, valine, isoleucine, phenylalanine, and alanine" ) prepared to study... 

This question was examined with the aid of DL-tryptophan-[3- C]alanine prepared from Ba COs (60% isotopic excess). The C-labelled amino-acid was administered to the cultures of the organism, which then yielded 20 mg of labelled pyrrolnitrin containing 28.5 atom % excess C. 

Simple esters cannot be allylated with allyl acetates, but the Schiff base 109 derived from o -amino acid esters such as glycine or alanine is allylated with allyl acetate. In this way. the o-allyl-a-amino acid 110 can be prepared after hydrolysis[34]. The Q-allyl-o-aminophosphonate 112 is prepared by allylation of the Schiff base 111 of diethyl aminomethylphosphonates. [35,36]. Asymmetric synthesis in this reaction using the (+ )-A, jV-dicyclohex-ylsulfamoylisobornyl alcohol ester of glycine and DIOP as a chiral ligand achieved 99% ec[72]. 

A more challenging problem is to find the pH of a solution prepared from a polyprotic acid or one of its conjugate species. As an example, we will use the amino acid alanine whose structure and acid dissociation constants are shown in Figure 6.11. 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

R)-Calcium pantothenate (3) is prepared by condensing (R)-pantolactone (9) with P-alanine (10) in the presence of base, followed by treatment of the sodium salt (11) with calcium hydroxide. 

The resulting -aminocaproic acid hydrochloride is treated in a manner similar to that used in the preparation of df-alanine (Org. Syn. Coll. Vol. i, 20). The hydrochloride is dissolved in r 1. of water in a 1.5-I. beaker and treated successively with 50 g. of powdered litharge, 25 g. of powdered litharge, 5 g. of freshly precipitated lead hydroxide, 25 g. of powdered silver oxide (Note 2), and finally hydrogen sulfide. During this procedure, the original volume is maintained by the addition of small amounts of water. 

N-Phthalyl-L-phenylalanine has been prepared by the fusion of L-alanine with phthalic anhydride. 

Saturated azlactones such as 18 and 29a, whose preparation is discussed in parts 2, b and 3 of this section, are useful intermediates for the synthesis of a variety of j8,j8-disubstituted alanines (32). ... 

A number of new j8-substituted alanines have been prepared from unsaturated azlactones by the usual reduction-hydrolysis procedures. An interesting example is the synthesis of DL-jS-ferrocenylalanine (33). ... 

The member of this class which has been studied most thoroughly is 2-benzylidene-4-methyl-5(2 )-oxazolone (57). This compound may be prepared by ring closure of either 3-bromo-2-phenylacetamido-propionic acid or A-(a-halophenylacetyl)alanine (56) [Eq. (30)]. These reactions presumably proceed via unstable halogeno-5(4IT)-oxazolones, which rapidly lose hydrogen halide. 

An ester of alanine with an arylaliphatic alcohol has shown promise as a non-tricyclic antidepressant. It may be speculated that the hindered milieu of the ester linkage protects the compound from hydrolysis by endogenous esterases. The preparation starts by reaction of pheny-lacctate 83 with methyl magnesium iodide to give tertiary carbinol 84. Acylation with 2-bromo-]>ropionyl bromide leads to ester 85 displacement of halogen with ammonia leads to alaproclate ( 6) [211. 

Amino acids can be prepared by reaction of alkyl halides with diethyl acelamidomalonate, followed by heating the initial alkylation product with aqueous 1-ICl. Show how you would prepare alanine, CH3CH(NH2)C02H, one of the twenty amino acids found in proteins, and propose a mechanism for acid-catalyzed conversion of the initial alkylation product to the amino acid. 

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. 

L-alanine can be prepared from aspartic acid (Figure A8.13). L-Aspartate-(5-decarboxylase produced by Xanthomonas oryzae No 531 has been used to prepared L-alanine in 95% yield from 15% L-aspartic add solution. Other strains, ie Pseudomonas dacunhae or Achromobacter pestifer, give comparable yields of L-alanine. The process has been commercialised by Tanabe. 

In order to prove the utility of this method and to ascertain the absolute configuration of the products, (S)-alanine has been enantioselectively prepared. The key step is the addition of methyllithium to the AjA -dimethyl hydrazone acetal 4c, derived from diol 3c. In accordance with 13C-NMR investigations it can therefore be assumed that all major diastereomers resulting from the addition of organolithium reagents to hydrazone acetals 4a-c derived from diols 3a, 3b or 3c (Table 3, entries 1 -6) have an S configuration at the newly formed stereogenic center. 

Aminopropanoic acid O-alanine) is available from Aldrich Chemical Company, Inc., and from the Nutritional Biochemical Division, TCN Products. The hydrochloride salt is prepared in the following manner. A solution of 89 g. (1.0 mole) of 3-aminopropanoic acid in 200 ml. of water is acidified by addition of 100 ml. (1.2 mole) of concentrated hydrochloric acid and then concentrated to a white solid with a rotary evaporator. The solid is pulverized to a fine powder and dried at 60° under reduced pressure. The yield of 3-aminopropanoic acid hydrochloride amounts to 113-125 g. (90-100%). 

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