II. CHEMISTRY 551 



(//-Xordesthiohiotin was synthesized in a similar manner. A very similar 

 method for proi)arinj!; desthiobiotin was used by Swain, '^'^ except that the 

 amino group was introtluced by chlorination with sulfuryl chloride, fol- 

 lowed by amination with potassium phthalimide. 



A further method for the synthesis ol" desthiobiotin, also applicable for 

 the synthesis of its liigher homolog, homodesthiobiotin, was devised by 

 IMcKennis and du Vigneaud«9 (XVII-XXII). 



C,Il500C(CIIo)7-COCl C'(CH,). _^ C..H500C-(CH2)7-CO-CH3 — C^H^NO?_^ 

 XVII XVIII 



The synthesis of ti/-hexahydro-2-oxo-lH-furo[3,4]imidazole-4-valeric 

 acid, the oxygen analog of biotin was reported almost simultaneously by 

 Hofmann^"' ^^ and by Duschinsky and his associates.'^- The compound is 

 called oxybiotin" or O-heterobiotin." Among the possible stereoismeric 

 forms only the two m-3,4-diamino-2-tetrahydrofuranvaleric acids formed 

 l)icyelic urea derivatives. Thus, it appears that the tetrahydrofuran is more 

 planar in its configuration than the tetrahydrothiophene ring, which ap- 

 parently permits the formation of ^rans-urea derivatives. 



«8 G. Swain, /. Chem. Soc. 1948, 1552. 



«9 H. McKennis and V. du Vigneaud, /. Biol. Chem. 68, 1.507 (1946). 



'0 K. Hofmann, J. Am. Chem. Soc. 67, 694 (1945). 



" K. Hofmann, J. Am. Chem. Soc. 67, 1459 (1945). 



" R. Duschinsky, L. A. Dolan, D. Flower, and S. H. Rubin, .{rch. Biochem. 6, 480 



(1945). 

 " F. J. Pilgrim, A. E. Axelrod, T. Winnick, and K. Hofmann, Science 102, 35 (1945). 



