760 Colchicine 



scribed by Zeisel.^ Although under suitable conditions colchicine 

 forms precipitates with many ot the usual alkaloidal reagents,^ its 

 classification as an alkaloid is questionable. It is essentially a neutral 

 substance with a honiocyclic ring-structure: on the other hand, it is 

 associated in the plant with compounds of allied structure, some seven 

 crystalline and kindred alkaloids being known (Santavy and Reich- 

 stein**) . 



6.2: The Functional Groups 



Hydrolysis of colchicine by boiling with very dilute hydrochloric 

 acid yields methyl alcohol and colchiceinc, C^iH^.^OuN, which is 

 acidic, gives a deep olive-green color with aqueous ferric chloride 

 (distinction from colchicine) , and on further hydrolysis with more 

 concentrated acid yields equivalent amounts of acetic acid and tn- 

 mcthylcokhicinic acid, Ci.,HoiOr,N (ZeiseP) . This last compound is 

 amphoteric and contains a primary amino-group (Johanny and 

 Zeiseli") ; hence the two-stage hydrolysis may be represented as follows: 



C10H1SO4 (OMe) (NH.COMe) 



-^ MeOH + Cic,Hi,04 (OH) (NH.COMe) 

 -> MeCOoH + CigHisO, (OH) (NH,) . 



Trimethykolchicinic acid contains three methoxyl groups which, by 

 prolonged hydrolysis, are demethylated and colchicinic acid, CifiHig 

 O5N, is produced. Correspondingly in colchicine itself the presence 

 of four methoxyl groups is shown by the usual Zeisel estimation.^ 



The four methoxyl groups and the acetylamido-group together 

 account for five of the six oxygen atoms of colchicine. Since the sixth 

 oxygen is unresponsive to carbonyl reagents, it was at one time 

 thought to be part of a carbomethoxy group (-CO.OMe) or of an 

 oxygen ring system. The former view is in harmony with the ready 

 hydrolysis to colchiceinc which has acidic character but which, on 

 the other hand, also shows definite enolic properties and when methyl- 

 ated by diazomethanc, yields two readily hydroly/able O-methyl 

 ethers, namely colchicine and iaocolchicine (Meyer and Reichstein;ii 

 Sorkini-) . Similarly trimethykolchicinic acid reacts with benzenesul- 

 phonyl chloride to give two di (benzenesulphonyl) derivatives (W^in- 

 daus^^^) , in each of which one of the acyl gioups is attached to nitro- 

 gen while the second ajjpears to be attached to oxygen since fairly 

 mild hydrolysis converts both compounds into the same A^-benzenesul- 

 phonyl trimethylcolchicinic acid. This duplication of O-derivatives 

 strongly suggests that in colchiceinc and in trimethylcolchicinic acid 

 there is a tautomeric enol system capable of giving rise to paired O- 

 derivatives which are either steric or structural isomers. Accordingly 

 the sixth oxygen atom is considered to reside in the carbonyl group 



