Stereoisomers of hydroxyproline.

Hydroxy-L-proline was first isolated by Fischer in 1902 from a hydrolysate of gelatin (l).l The synthesis and determination of the structure were reported by Leuchs and coworkers (5--g), and, in 1919, the separation of the two racemic stereoisomers and the resolution of each racemate through mixtures of quinine with the corresponding N-phenylisocyanate derivatives were accomplished (5). In the present nomenclature, [LY]~ for hydroxy-L-proline was -75.7”, for hydroxy-n-proline, +75.2”, for allohydroxy-L-proline, --5&l”, and for allohydroxy-n-proline, +58.6’ (5). Not only hydroxy-L-proline but also allohydroxy-L-proline occurs in nature, for the latter’ has been isolated by Wieland and Witkop from the toxic peptide of Amunita phalloides (10). The assignment of the L configuration to the allostereoisomer with [CLI]~ = -58.1” was due to the work of Neuberger, who converted hydroxy+ proline to allohydroxy-L-proline by inverting the configuration at Cd (3). This procedure involved the following steps: acetylation of the NH group of hydroxy-L-proline, esterification with diazomethane, formation of the 0-toluenesulfonyl ether at Cd by treatment of the N-acetyl-hydroxy-Lproline methyl ester with p-toluenesulfonyl chloride in dry pyridine solution, saponification of the carboxylic ester at low temperature, alkaline fission of the 0-toluenesulfonyl ether at high temperature (which is the