830 X. THE VITAMIN K GROUP 



demonstrated by several groups of workers in the United States,^-^ as well 

 as by Dam and Glavind^"-" in Denmark. 



Vitamin K was first shown to be present in lettuce. It was later found 

 in hog-liver fat, hempseed, tomatoes, kale,^ and to a small extent in a 

 number of cereals.^ Halbrook^^ reported, as early as 1935, that the de- 

 ficiency in chicks could be prevented when 5% of dehydrated alfalfa was 

 included in the diet, or when fish meal which had been kept moistened for a 

 period of time was employed as a source of protein. Almquist and Stok- 

 stad^' isolated the active principle from the non-saponifiable fraction of 

 alfalfa lipid. It was proven to be stable to heating in an oven at 120°C. for 

 24 hours. Neither chlorophylls, sterols, carotene, nor xanthophylls 

 were shown to have any antihemorrhagic effect. Moreover, the active 

 component possessed no acidic or basic properties, nor was it found to be an 

 ester. 



Pure vitamin K was first isolated in 1939, almost simultaneously by the 

 Dam-Karrer group^"* and by Doisy and co-workers. ^^ The products pre- 

 pared from alfalfa by Dam et al.,^^ and also by MacCorquodale et al., dif- 

 fered both in physical and in chemical properties from that separated from 

 putrefied fish meal by McKee and associates. ^^-^ Both preparations had 

 approximately the same activity as antihemorrhagic agents. It therefore 

 became evident that more than one product possesses antihemorrhagic 

 activity. The compounds isolated from alfalfa and from putrefied fish 

 were designated as vitamins Ki and K2, respectively. 



The chemical nature of both of these vitamins was elucidated very soon 

 after their separation in pure form. The structure of vitamin Ki, with 

 proof of its synthesis, was announced simultaneously by Almquist and 

 Klose,^^ Binkley et al.^^ of the Doisy group, and by Fieser.^" The foUow- 



8 E. D. Warner, K. M. Brinkhous, and H. P. Smith, Proc. Soc. Exptl. Biol. Med., 37, 

 628-630 (1938). 



9 H. R. Butt, A. M. Snell, and A. E. Osterberg, Proc. Staff Meetings Mayo Clinic, 13, 

 74-80 (1938). 



10 H. Dam and J. Glavind, Lancet, 234, 720-721 (1938). 



" H. Dam and J. Glavind, Acta Med. Scand., 96, 108-128 (1938). 



12 E. R. Halbrook, Thesis, Univ. Calif. (1935). Cited by H. J. Almquist and E. L. R. 

 Stokstad, J. Biol. Chem., Ill, 105 (1935). 



13 H. J. Almquist and E. L. R. Stokstad, /. Biol. Chem., Ill, 105-113 (1935). 



1^ H. Dam, E. Geiger, J. Glavind, P. Karrer, W. Karrer, E. Rothschild, and H. Salo- 

 mon, Helv. Chim. Acta, 22, 310-313 (1939). 



>5 D. W. MacCorquodale, S. B. Binkley, R. W. McKee, S. A. Thayer, and E. A. Doisy, 

 Proc. Soc. Exptl. Biol. Med., 40, 482^83 (1939). 



" R. W. McKee, S. B. Binkley, D. W. MacCorquodale, S. A. Thayer, and E. A. Doisy, 

 J. Am. Chem. Soc, 61, 1295 (1939). 



" R. W. McKee, S. B. Binkley, S. A. Thayer, D. W. MacCorquodale, and E. A. Doisy, 

 J. Biol. Chem., 131, 327-344 (1939). 



>8 H. J. Almquist and A. A. Klose, J. Am. Chem. Soc, 61, 2557-2558 (1939). 



19 S. B. Binkley, L. C. Cheney, W. F. Holcomb, R. W. McKee, S. A. Thayer, D. W. 

 MacCorquodale," and E. A. Doisy, J. Am. Chem. Soc, 61, 2558-2559 (1939). 



2» L. F. Fieser, /. Am. Chem. Soc, 61, 2559-2561 (1939). 



