Biopotency of vitamin K. I. Antihemorrhagic properties of structural analogs of phylloquinone as determined by curative prothrombin time tests
Weiser, H.; Kormann, A.W.
International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift für Vitamin- und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition 53(2): 143-155
1983
ISSN/ISBN: 0300-9831 PMID: 6885274 Document Number: 213210
Relative antihemorrhagic properties of structural analogs of transphylloquinone (vitamin K1) were determined by curative prothrombin time tests with vitamin K-deficient chicks. Analogs (where applicable) and the phylloquinone standard had (all-) rac-trans configuration, and all compounds were well characterized (structure, purity, trans:cis). Compounds were administered as single oral doses according to the up-and-down procedure. Estimation of mean effective doses allowed a reliable calculation of relative activities for analogs in comparison with vitamin K1 standard. 2',3'-Dihydro-phylloquinone had a relative activity of only 6.7%, i.e., it was about 15 times less active than phylloquinone. Further reduction of this analog led to 2',3',5,6,7,8-hexahydro-phylloquinone which was completely inactive. Analogs with O2 functions in the side chain, 6'-hydroxy-K1, 6'-oxo-K1 and 7'-hydroxy-6'-oxo-K1, displayed relative activities of 20.5, 31.9 and 30.5%, respectively. Phylloquinone-2,3-epoxide was 1.7 times more active than the phylloquinine standard. An analog with a 7-carbon side chain ending with a carboxyl group (in mammals a urinary metabolite of vitamin K1) and its corresponding ethyl ester derivative were practically inactive.