THE CHEMICAL CONSTITUTION OF THE UNITS 141 



The third method of separating optically active substances by com- 

 bining them with optically active bases, or acids, had not been employed 

 with any success with the amino acids until E. Fischer took up this 

 question, the study of the optically active amino acids being his first 

 work upon the chemical constitution of the proteins. The non-suc- 

 cess of this method was in all probability due to the small affinity 

 which the simple amino acids themselves have for combining with 

 acids and bases ; even the attempts to separate the monoaminodi- 

 carboxylic acids, which are fairly strong acids, were not successful. 



Hippuric acid, or benzoylglycine, has been known for a long time, 

 and by preparing the benzoyl derivatives of the other amino acids, 

 Fischer found that their acidic character was greatly increased, and that 

 they then combined with the optically active bases brucine, strychnine, 

 cinchonine, morphine, forming stable salts. These salts were much 

 less soluble and their power of crystallising much greater than the salts 

 of the amino acids themselves, and consequently they were more easily 

 isolated ; further, they were easily reconverted into the amino acids. 



These benzoyl derivatives were prepared by shaking the amino 

 acid with excess of benzoyl chloride in the presence of sodium bi- 

 carbonate instead of in the presence of excess of alkali, i.e., by the 

 Schotten-Baumann method, which gave poor and varying yields of the 

 benzoyl compound. 



Alanine, aspartic acid, glutamic acid, tyrosine, leucine, phenyl- 

 alanine and also a-amino-n-caproic acid and a-aminobutyric acid have 

 in this way been separated by Fischer into their optically active iso- 

 mers. To these must be added ornithine which was synthesised by 

 Sorensen in 1903, and separated into d- and 1-ornithine in 1905. 



Not only can the benzoyl derivative be employed for this purpose 

 but also the formyl derivative which is prepared by heating the amino 

 acid with anhydrous formic acid at 100 C. These formyl derivatives 

 also give beautifully crystalline salts with the optically active bases, and 

 they possess one great advantage over the benzoyl derivatives, namely, 

 that the formyl group is easily removed by hydrolysis, whereas the ben- 

 zoyl group requires prolonged heating with a large excess of acid for 

 its removal. The formyl derivative is of enormous advantage also for 

 building up optically active polypeptides, as it admits of the prepara- 

 tion of large quantities of the optically active amino acids. 



Fischer and his pupils have thus prepared the optically active forms 

 of leucine, phenylalanine, and valine, and also of phenylaminoacetic 

 acid, a-amino-n-caproic acid and /5-amino-/3-phenyl propionic acid 



