Emil Fischers Work

Under the influence of E. Fischer s extensive chemical studies on protein structure, Curtius extended his method to the synthesis of benzoylated peptides containing alanine and aspartic acid, but left the peptide field after 1905. The 7-Saure had been recognized as benzoylhexaglycine, the Biuretbase as tetragly-cine ethylester. For a summary of his 23-years involvement see Ref. [6]. 

Most certainly, Curtius did not intend to enter protein chemistry when he started his work on hippuric acid and glycine. In the following years he was mainly fascinated by his discovery of diazo-fatty acid esters and the multitude of their reactions and so scarcely acquired interest in peptones and albuminoids. During the last decade of the past century, however, stimulated by E. Fischer s vigorous activity, Curtius resumed his studies, by which he contributed so much to modern peptide chemistry. It is somewhat ironical that Fischer s engagement, that had an immense echo at that time left less practical application for peptide chemistry than Curtius invention of the azide coupling method. Emil Fischer s great merit is to have drawn the attention of the whole scientific world to the field of proteins, whose mystery could be revealed by application of chemical methods and to lend trust to chemists that they are able to synthesize complicated natural substances like peptides. 

Three topics in this field still awaited experimental work. The first was to work out methods to separate qualitatively the mixture of amino acids in a hydrolyzate, and, if possible at all, to determine their respective amounts. The second was to optimize the syntheses and to resolve racemic mixtures in order to obtain the natural enantiomers. The third aim was to modify the amino acids to make them useful for the intended coupling reactions. 

For the separation and the putative detection of new amino acids Fischer introduced the ester method . As Curtius already had described nearly 20 years before, amino acids were treated with HCl in absolute ethanol yielding the ester hydrochlorides from which Curtius had obtained the free esters by means of silver oxide. Fischer simplified the procedure by adding sodium hydroxide to the 

The second task, resolution of synthetic D,L-amino acids has been solved by conversion of the neutral amino acids into real carboxyUc acids by acylation of the amino group, either by the benzoyl or the formyl residue. The D,L-acyl amino acids then formed diastereomeric salts with optically active bases, mostly alkaloids, which differed in their solubihty in various solvents, and so could be separated by recrystallization. This method is still in use, although enzymatic procedures, specific oxidation of the D-antipode in the presence of D-amino acid oxidase or enzymatic, stereospecific removal of iV-acyl residues from d,l-AT-acetyl-amino acids by acylase, are more convenient. Certainly, L-amino acids became accessible from nature by the ester method, but without synthetic material, extended experiments of peptide couphng would have been impossible. 

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Hermann Emil Fischer Work on sugar and purine syntheses... 

Of all the monosaccharides d (+) glucose is the best known most important and most abundant Its formation from carbon dioxide water and sunlight is the central theme of photosynthesis Carbohydrate formation by photosynthesis is estimated to be on the order of 10 tons per year a source of stored energy utilized directly or indi rectly by all higher forms of life on the planet Glucose was isolated from raisins m 1747 and by hydrolysis of starch m 1811 Its structure was determined in work culmi nating m 1900 by Emil Fischer... 

In 1951, he received the Emil Fischer Medal of the Gesellschaft Deutscher Chemiker, and in 1957, the Grosse Verdienstkreuz (Grand Service Cross) of the Federal Republic of Germany. The Technische Hochschule in Stuttgart conferred upon him the honorary doctorate of Dr. ing. h.c. The Saxon Academy of Science and the Leopoldina in Halle, East Germany, elected him an honorary member. His scientific work, which found expression in 328 publications and 16 patents, is characterized by originality and a comprehensive command of experimental method. 

Fischer s Convention. Initially, the absolute configurations of optical isomers were unknown to chemists working with optically active compounds. Emil Fischer, the father of carbohydrate chemistry, decided to relate the possible configurations of compounds to that of glyceraldehyde of which the absolute configuration was yet unknown but was defined arbitrarily. 

He never gave unbridled rein to his synthetic efforts, nor did he fall into the temptation of purposeless synthesis. He always remained a true scientist—a student of nature.. . . This great individual was a man of inflexible veracity and simplicity.. . . Emil Fischer s life was based on responsibility a responsibilityfor the austerity andpurity of his work and its aims, responsibility for the university as an important organ of our cultural and economic life, and responsibility for each of his students. 

The fundamental principles governing the spatial isomerism of the simple sugars and the theoretical and experimental work of Emil Fischer cannot be dealt with here. Those who are not already familiar with the subject should at once fill this gap in their knowledge they are emphatically advised to use space models. 

It is of some historical interest that Kiliani s cyanohydrin synthesis (24) enabled Emil Fischer (25) to carry out the first asymmetric synthesis. Lapworth (26) used this base-catalyzed nucleophilic 1,2-addition reaction in one of the first studies of a reaction mechanism. Bredig (27,28) appears to have been the first to use quinine (29) in this reaction as the chiral basic catalyst. More recently, others (20) have used basic polymers to catalyze the addition of cyanide to aldehydes. The structure of quinine has been known since 1908 (30). Yet it is of critical importance that Prelog s seminal work on the mechanism of this asymmetric transformation (eq. [4]) could not have begun (16) until the configuration of quinine was established in 1944 (31,32). 

Investigations upon their chemical constitution have been carried on now for nearly a century, but it is only during the last ten years that, by the work of Emil Fischer and his pupils, any clear view has really been obtained of their actual constitution. The main result of these investigations is that the protein molecule is built up of a series of amino acids, which form the basis of their composition, and of which the following have been definitely determined —... 

The presence of diamino acids in all proteins led Kossel to suppose that there was a protamine nucleus (t.e, of diamino acids) in all proteins the more recent work, especially that by Osborne and Clapp on the gliadins, where the diamino acids are present in such small amounts, though it supports the theory, yet suggests that proteins may exist in which it is not present, more especially if the view of Emil Fischer be taken that all the proteins we know, even the crystalline ones, are still mixtures of several proteins. The isolation of complexes containing only diamino acids from proteins, where they are combined together, will be the only proof of a protamine nucleus in a protein molecule. 

After the pioneering work of Louis Pasteur and Emil Fischer in the middle and at the end of the nineteenth century, respectively, it still took more than fifty years before chemists started to discuss transition state models together with polar and steric effects to gain more insight into the phenomenon of asymmetric induction. Even first observations in organic synthesis of enantioselectivities comparable to those of enzymes in the late fifties and sixties of the 20 century did not convince the chemical community and the term asymmetric synthesis was regarded a mechanistic curiosity rather than a practical way to synthesize compounds of high enantiomeric purity. 

H. Kiliani, Uber das Cyanhydrin der Lavulosc, Ber. Dtsch. Chem. Ges. 18 3066 (1885) E. Fischer, Reduction von Sauren der Zuckergnippe, Ber. Dtsch. Chem. Ges. 22 2204 (1889). For recent historical review articles dealing with the work of Emil Fischer on the configuration of sugars, see ... 

Emil Fischer himself collected, and edited, the greater part of his own work in the carbohydrate field in his well-known book Untersuchungen liber Kohlenhydrate und Fermente. This volume was completed in 1908. Subsequent work was compiled under the same title by Max Bergmann, Fischer s student and faithful assistant this second volume was published in 1922. Both volumes contain a list of the titles and places of journal publication of his papers, as well as a subject index to them. The present author accordingly considers it unnecessary to cite references here. In a few instances, work is described which appeared subsequent to 1922. 

When Emil Fischer died in August, 1919, at the age of 67 years, he bequeathed a life-work of rare comprehensiveness. He had contributed greatly to our knowledge of the material world, and especially to that of organisms. He refocused the thinking in organic chemistry back to its starting point, the world of animated Nature. 

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