Isoleucine

The sec.-butylmalonic acid is extracted with three 200-cc. portions of ether, and the combined extracts are dried over calcium chloride overnight. The ether solution is then decanted into a 2-1. three-necked flask fitted with a mercury-sealed stirrer, reflux condenser, and dropping funnel. Five cubic centimeters of bromine is added at one time and the solution stirred until decolorized (Note 7). Then 50 cc. more bromine is added drop-wise at such a rate that the ether refluxes gently. When all the bromine has been added, 200 cc. of water is added through 

The ether layer containing the bromomalonic acid is separated from the aqueous layer and the ether removed by distillation from a steam cone. The residual liquid is decarboxylated by refluxing for five hours in a 500-cc. round-bottomed flask on an oil bath heated to 130°. The bromo acid is then separated from the small amount of water and distilled. The material distilling at i25-i4o°/i8-2o mm. is a-bromo- -methylvaleric acid (Note 8). The yield is 150.5 g. (66.7 per cent of the theoretical amount). 

The isoleucine is recrystallized by dissolving it in 850 cc. of water heated to 950 on a steam cone. The solution is decolorized by treatment with a gram of Norite for thirty minutes and is then filtered hot. To the hot solution is added 425 cc. of 95 per cent alcohol, and the flask is placed in an icechest overnight. The yield of pure product is 38 g. An additional crop of 12 g. may be obtained by concentrating the mother liquors from the recrystallization to about 100 cc. and adding an equal volume of alcohol. This second crop is washed with 10 cc. of cold water and 10 cc. of cold alcohol. The total yield is 50 g. (49 per cent of the theoretical amount). The product decomposes at 278-280° in a sealed evacuated capillary (Note 10). 

The submitters carried out the preparation on a run ten times this size, using a 12-I. round-bottomed flask. After the sodium had reacted, the flask was fitted with a stopper containing the stirrer and two angle tubes connected respectively to a reflux condenser and a dropping funnel. The time allowed for the various reactions to take place was the same as for the smaller run. The percentage yields of the various products were practically identical. 

On a run ten times this size, the submitters distilled the alcohol into another 12-I. flask connected by means of an adapter and fitted with the wide-bore reflux condenser originally used. The sodium necessary for a second run was added to the second flask as the alcohol distilled into it on the large run this took four to six hours. 

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Figure 7-14. All-atom and united-atom representation of the amino acid isoleucine. In this example, 13 atoms, which are able to form explicit non-bonding interactions, are reduced to only four pseudo-atoms,...

Diamide Chiral Separations. The first chiral stationary phase for gas chromatography was reported by GH-Av and co-workers in 1966 (113) and was based on A/-trifluoroacetyl (A/-TFA) L-isoleucine lauryl ester coated on an inert packing material. It was used to resolve the tritiuoroacetylated derivatives of amino acids. Related chiral selectors used by other workers included -dodecanoyl-L-valine-/-butylamide and... 

Herbicides also inhibit 5- (9/-pymvylshikiniate synthase, a susceptible en2yme in the pathway to the aromatic amino acids, phenylalanine, tyrosine and tryptophan, and to the phenylpropanes. Acetolactate synthase, or acetohydroxy acid synthase, a key en2yme in the synthesis of the branched-chain amino acids isoleucine and valine, is also sensitive to some herbicides. Glyphosate (26), the sulfonylureas (136), and the imida2oles (137) all inhibit specific en2ymes in amino acid synthesis pathways. 

The asterisk signifies an asymmetric carbon. AH of the amino acids, except glycine, have two optically active isomers designated D- or L-. Isoleucine and threonine also have centers of asymmetry at their P-carbon atoms (1,10). Protein amino acids are of the L-a-form (1,10) as illustrated in Table 1. 

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