Synthesis of Hydroxylysine By


Hydroxylysine was first recognized as a constituent of protein hydrolysates by Van Slyke and Hiller (1) who in later work (2) established a procedure whereby the relatively pure amino acid could be separated from the lysine fraction by fractional precipitation of the picrates. Van Slyke, Hiller, and MacFadyen (3) studied the reaction of hydroxylysine with periodate in alkaline solution and developed a method for determining hydroxylysine in protein hydrolysates. The periodate reaction, which is specific to vicinal glycols and ethanolamines (4), was shown by Van Slyke, Hiller, MacFadyen, Hastings, and Klemperer (5) to liberate 1 molecule of formaldehyde and 1 molecule of ammonia from hydroxylysine, thus establishing that one of the vicinal ethanolamine carbons was terminal. The influence of the hydroxyl group on the basicity of the amino groups as compared with lysine was studied by Klemperer, Hastings, and Van Slyke (6) and observed to agree with the assumption that the hydroxyl group was vicinal to the more basic (non+) amino group. These findings established the structure of hydroxylysine as either 2,5-diamino-6-hydroxycaproic acid or as 2,6-diamino-5-hydroxycaproic acid. Recently Bergstrijm and Lindstedt (7) have isolated natural hydroxylysine and prepared the dibenzoyl derivative in which they demonstrated the hydroxyl group to be in the 5 position by oxidation with chromic acid. 2 equivalents of chromic acid were utilized to yield 5-ketolysine rather than the 4 equivalents required by the structural isomer to give 2,5-diaminoadipic acid. They also demonstrated the reduction of hydroxylysine to lysine by the action of hydriodic acid and phosphorus. The present work confirms this structure by synthesis of the diastereoisomers and separation of a derivative of the L isomer having identical properties with t,he same derivative prepared from hydroxy+lysine of natural origin. The introduction of four functional groups into the B-carbon structure of hydroxylysine requires reactions which do not affect irreversibly any of these groups. The synthesis has been carried out by introducing the hydroxyl and terminal amino groups as a final step under sufficiently mild conditions to restrict secondary reactions. The intermediary com-

Cite this paper

@inproceedings{Weisiger2003SynthesisOH, title={Synthesis of Hydroxylysine By}, author={J R Weisiger and Elizabeth A. Jacobs}, year={2003} }