The Isolation of Pure Amino Acids *

There are two principal methods for the preparation of large amounts of amino acids. The first of these is synthesis by a rich variety of methods, some of which are the result of brilliant experimental work performed during the past decade by Albertson and Suter, Snyder, Dunn, Marvel, and others. It is the purpose of this paper to consider several aspects of the second principal method for the preparation of amino acids, namely, their isolation from natural products. Historically, of course, the isolation of amino acids antedated their synthesis. It was Wollaston who, by his discovery in urinary calculi of what was later called cystine, in 1810 initiated the efforts directed toward the isolation of amino acids. The demonstration that this sulfur-containing amino acid could be isolated upon hydrolysis of proteins came much later, in 1899. The honor of being first recognized as protein constituents fell rather to two other amino acids, glycine and leucine, which were isolated in 1820 by Bracconot from a sulfuric acid hydrolysate of gelatin. The material named leucine had also been obtained the year before, in 1819, by Proust from an aqueous extract of fermented gluten. These discoveries set the stage for the development of protein chemistry and during the succeeding years, the methods introduced by the early pioneers were notably extended by many investigators, among whom are numbered such luminaries of science as Liebig, Ritthausen, Schulze, and Emil Fischer.39 In principle, the procedures employed by these early workers for the hydrolysis of proteins to their constituent amino acids are still in use today. Thus, the acid hydrolysis of proteins, due to Bracconot, is still the most widely applied method for the cleavage of proteins, although the work of Bopp in 1849 and of Hlasewitz and Habermann in 1873 led to the use of hydrochloric acid in place of the sulfuric acid used by Bracconot. More recently, a valuable modification was introduced by Blumenthal and Clarke8 which involves the use of