552 



BIOTIN 



Hofmanii used the following scheme (XXIII-XXVIII) for the synthesis 

 of rf^oxybiotin^^ 



C2H5OOC COOC2H.S 



I I 



+ 



CH CH 



II II 



CH C-(CH2)4-CH20H 



\ / 

 O 



XXIII 



ClOC COCl 



I I 



c c 



II II 



CH C-(CH.,)4-CH20Ac 



\ / 



o 



XXV 



CO 



/ \ 



NH NH 



HOOC COOH 



1 1 



c c 



II II 



CH C-(CH2)4-CH20H 



\ / 

 O 



XXIV 



CiHsOOC-NH NHCOOC2H5 



I I 



c c 



II II 



CH CH-(CH2)4-CH20H 



\ / 

 O 



XXVI 

 CO 



/ \ 



NH NH 



C 



C 



H H 



CH2 CH(CH2)4-CH20H 



H H 



CH. CH-(CH2)4COOH 



XXVII 



XXVIIl 



Oxybiotin 



A series of homologs of oxybiotin, in which the side chain contained two 

 to six methylene groups/^ and their sulfonic acid analogs'^^"'^^ were also 

 synthesized. 



" K. Hofmann, C. Chen, A. Bridge water, and A. E. Axelrod, J . Am. Chem. Sac. 69, 



191 (1947). 

 '5 A. E. Axelrod and K. Hofmann, ,/. Biol. Chcm. 180, 525 (1949). 

 78 K. Hofmann, A. Bridgewater, and A. E. Axelrod, /. Am. Chem. Soc. 69, 1550 (1947). 

 " K. Hofmann, A. Bridgewater, and A. E. Axelrod, J. Am. Chimi.Soc. 71, 1253 (1949). 



