421 Thiophenes, Imidazoles, Thiazoles, Isoxazoles 



The same research group (Arnstein and collaborators) 

 has isolated a tripeptide from the mycelium of the com- 

 mercial penicillin producer, Penicillium chrysogennmJ 

 It is 8-(a-aminoadipyl) cysteinylvaline: 



HOOC— CH— CH.— CH.— CH2— CO— NH— CH— CO— NH— CH— COOH 



NH.> CH2SH CH 



/ \ 

 CH3 CH3 



5-(a-Aminoadipyl) cysteinylvaline 



Consistent with the above evidence, this is a cysteinyl- 

 valine. It is not difficult to envisage cyclization to form 

 synnematin B: 



HOOC— CH NH C=0 



CH3 1 I O 



\l I II 



CH CH2— CH— NH— C— CH2— CH2— CH2— CH— COOH 



/ / I 



CH3 S NH2 



H 



., — 4H 



HOOC— CH NH C=0 



CH3 I I I O 



\l I I II 



CH CH CH— NH— C— CH2— CH2— CH2— CH— COOH 



CH3 ^ NH2 



Interesting features of this discovery are, first, that a 

 side-chain is attached before cyclization to form 6-ami- 

 nopenicillanic acid and, second, that the side-chain is 

 a-aminoadipic acid, the side-chain of synnematin B (ceph- 

 alosporin N) which is not produced by Penicillium chrys- 

 ogenum. Perhaps side-chain exchange occurs after cy- 

 clization. The configurations of the amino acids in the 

 acyclic mycelial peptide have not been reported yet. 



The structure of cephalosporin C, a substance related 

 to synnematin B, is known, but has not yet been pub- 

 lished. 



Two reviews of the biosynthesis of penicillin are 

 cited.s '-> 



"^ H. R. V. Arnstein, D. Morris and E. Toms, Biochim. et Biophys. 

 Acta 35 561 (1959). 



® A. L. Demain, Advances in Appl. Microbiol. 1 23 (1959). 

 ®D. Hockenhull, Prog, in Ind. Microbiol. 1 1 (1959). 



