II. CIIExMISTRY 549 



\ 

 CO CH COOCH, C ^CH-COOCH, 



CH. CH(rH.)4C00CH, -ii^ HO CH2 CH-(CH2)4-COOCH, -^^^^^^ 



\ .. ' " \ / 



s s 



XXXIX XL 

 NC-C CHCOOCIT, IIOOCCH CHCOOII 



II I H^+ I I 



CH Cn(CH2)4COOCH3 — vThI-^ CII2 CH(CH2)C00H 



\ / " \ / 



s s 



XLI XLII 



This tricarboxylic acid (XLII) was converted into 2-(5-carboxybutyl)- 

 3,4-diaminothiophane by the selective degradation of the two nuclear 

 carboxyl groups without affecting the side-chain carboxyl group. On treat- 

 ment \\'ith phosgene this diaminocarboxylic yielded d/-epiallobiotin. Biotin 

 with the m configuration was prepared by a rather different series of re- 

 actions from a common intermediate, a m-uracil with the structure: 



C6H2 



/ 

 CO N 



/ \ 



HN CO 



\ / 



CH CH 



! I 



CH2 CH(CH2)4-COOH 



\ / 

 S 



A different type of synthesis is used for the industrial preparation of 

 biotin.^^ 



E. SYNTHESIS OF BIOTIN ANALOGS 

 1. Desthiobiotin 



The synthesis of desthiobiotin was accomplished in several ways. 



Melville®^ prepared it by the action of phosgene in alkaline solution on 

 its degradation product f ,7j-diaminopelargonic acid. Duschinsky and 

 Dolan®* used the following series of reactions (I-IX). 



83 M. W. Goldberg and L. H. Sternbach, U. S. Pats. 2,489,232-2,489,238, November 22, 



1949. 

 " D. B. Melville, J. Am. Chem. Soc. 66, 1422 (1944). 

 6» R. Duschinsky and L. A. Dolan, J. Am. Chem. Soc. 67, 2079 (1945). 



