BIOTIN 



References to Section 3 



1. V. du Vigneaud, K. Hofmann and D. B. Melville, /. Biol. Chem., 



1941, 140. 643. 



2. V. du Vigneaud, K. Hofmann, D. B. Melville and J, R. Rachele, 



ibid., 763. 



3. K, Hofmann, D. B. Melville and V. du Vigneaud, ibid., 207. 



4. F. Kogl and T. J. de Man, Z. physiol. Chem., 1941, 269, 81. 



5. K. Hofmann, D. B. Melville and V. du Vigneaud, /. Amer. Chem. 



Sac, 1941, 63, 3237 ; /. Biol. Chem., 1942, 144, 513. 



6. V. du Vigneaud, K. Hofmann and D. B. Melville, /. Amer. Chem. 



Soc, 1942, 64, 188. 



7. D. B. Melville, K. Hofmann and V. du Vigneaud, /. Biol. Chem., 



1942, 145, loi. 



8. V. du Vigneaud, D. B. Melville, K. Folkers, D. E. Wolf, R. Mozingo, 



J. C. Keresztesy and S. A. Harris, ibid., 1942, 146, 475. 



9. D. B. Melville, A. W. Moyer, K. Hofmann and V. du Vigneaud, 



ibid., 487. 



10. F. Kogl and L. Pons, Z. physiol. Chem., 1941, 269, 61. 



11. F. Kogl. H. Erxleben and J. H. Verbeck, ibid., 1942, 276, 63. 



12. F. Kogl, J. H. Verbeck, H. Erxleben and W. A. J. Borg, ibid., 



1943, 279, 121. 



13. F. Kogl and W. A. J. Borg, ibid., 1944, 281, 65. 



4. SYNTHESIS OF BIOTIN 



P-Biotin 



The formula assigned to j3-biotin was confirmed by synthesis. 

 This was accomplished in 1943 by Harris et al.^* 2, 3 according to the 

 following method, using L-cystine and chloroacetic acid as starting 

 materials : 



HOOC . CH , . S . CH2 . CH . COOH CH3OOC . CH^ . S . CH^ . CH . COOCH3 



NH2 NH.CO.CeHs 



NH . CO . C.Hs NH . CO . C,Yi, 



NaOCH, 



CH— C . ONa HCi CH— <:0 



I II ^11 



CH, C.COOCH3 CHa CHj 



\ / \/ 



S (I) S (II) 



NH . CO . C.Hs NH . CO . CeH, 



a 



OHC.(CH,),.coocH, CH — CO NH2OH CH — C=N . OH 



-f piperldlne acetate 



CH, 



I I 



C:CH.(CH,),.COOCH, CH^ C:CH. (CHs)s.COOCH, 



S (III) S (IV) 



414 



