Proline Oxyproline

Leuchs, in 1905, synthesised two stereoisomeric-7-oxy-prolines, one of which is probably the inactive form of the natural oxyproline. Epichlorhydrin and sodium malonic ester yield 7-chlor-/8-oxy-propyl-malonic ester, 

This compound on bromination, followed by hydrolysis of the ester group with hydrobromic acid and removal of carbon dioxide, gave a-brom-S-chlor-y-valerolactone, from which by treatment with ammonia 7-oxyproline was obtained — 

As this compound contains two asymmetric carbon atoms, four stereoisomeric forms are possible by synthesis these must occur in two inactive forms. These forms Leuchs separated by crystallisation of the copper salts, the more insoluble acid being termed (a)-7-oxy-proline, the other (b)-7-oxyproline. 

The constitution of these acids was confirmed in 1908 by Leuchs and Felser, who converted them, by reduction with hydriodic acid, into proline. Their attempt to determine whether natural oxyproline was the active form of one of the synthetical compounds by converting the natural substance into its racemic form by heating with baryta to 200° C. was unsuccessful, since complete racemisation did not occur. As, however, all compounds containing one asymmetric carbon atom to which a carboxyl group is attached are easily racemised, the result led to the conclusion that oxyproline contains two asymmetric carbon atoms. Of the four possible formulae, 

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Proline Oxyproline Aspartic Acid Glutamic Acid Tryptophane Arginine. Lysine Histidine. Diaminotrioxy dodecanic Acid... 

Even though these analytical figures are similar to those of proteins and polypeptides, no polypeptides of the usual type were present. After hydrolysis, a-amino acids were present only in small quantities, if at all. Boiling the hydrolyzed neutral solution with copper carbonate failed to yield the blue coloration characteristic of the a-amino acids. After 6 N acid hydrolysis, the amino N rose from 0.8% to 9% and after tryptic hydrolysis to 2%. Among the amino acids present were arginine and tyrosine but no phenylalanine, proline, oxyproline, glycine, tryptophan, and histidine. The procedure used by Karrer follows in Table VIII. 

Proline.—Two of the amino acids obtained as hydrolytic cleavage products of proteins are derivatives of pyrrolidine. They are proline and oxyproline (p. 392). Proline is a//>/fa-pyrrolidine carboxylic acid. 

Die beim Umsatz von Ninhydrin mit Aminosauren, auch mit Prolin und Oxyprolin gebildete C02 Menge ist quantitativ und ein MaB fur die Anzahl... 

L3. Lang, K., Eine Mikromethode zur Bestimmung des Prolins und des Oxyprolins. Z. Physiol. Chem. 219, 148-154 (1933). 

W7. Wiss, von O., Uber eine Mikrobestimmung des Oxyprolins in Blut und Ham Beeinflussimg des Oxyprolin-gehaltes duroh Verabreichung von Prolin. Hdv. Chim. Acta 32, 149-153 (1949). 

Procedure Two drops of the reagent are added to t ml of a neutral amino acid solution and the mixture is heated over a water bath. Red to violet color is formed with most amino acids proline and oxyproline give yellow colors. 

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