162 Colchicine 



in se\eral ways: (1) directly, by heating with phosphoric oxide in 

 xylene (Cook and Graham;i^ Barton, Cook, and Loudon^o) whereby 

 two isomeric compounds, Cif,H2i04. are formed and are named de- 

 amjuocolchinol methyl ether and hodeammocolchinol methyl ether, re- 

 spectively; (2) by hydrolysis to the primary amine, colchinol methyl 

 ether, followed by reaction with nitrous acid to form a carbinol 



CO2H 



COoH 



(Cohen, Cook, and Roe-^) which on dehydration^^ yields the same 

 pair of isomeric products; (3) by Hofmann degradation of colchinol 

 methyl ether whereby only deaminocolchinol methyl ether has been 

 isolated (Windaus--) . 



Barton, Cook, and Loudon-'^^' established the structure (II) for 

 deaminocolchinol methyl ether and the structure (III) for the iso- 

 compound on the following grounds. Both isomers afforded the same 

 dihydride when hydrogenated in acetic acid with a palladium cata- 

 lyst; they must therefore differ only in the location of a double Ijond 

 which must be ethylenic in type. Deaminocolchinol methyl ether was 

 oxidized with sodium dichromate in acetic acid to 2:3:4:7-tetrametho- 

 xyphenanthraquinone (VIII) , together with a by-product which was 

 recognized as an unsaturated ketone, CioHisOr,. 



Formation of the quinone, which was identified by synthesis, 

 establishes the presence of a (bridged) diphenyl system and fixes the 

 methoxylation pattern. The nature of the three-carbon bridge in 

 deaminocolchinol methyl ether (II) was next determined by oxida- 

 tion with osmium tetroxide to a glycol (IV) which, by scission with 

 lead tetra-acetate, yielded not the normally expected di-aldehyde (V) 

 but a mono-aldehyde (VI) formed from (V) by internal condensation. 

 This mono-aldehyde — later synthesized —was identified by oxidation 

 to 2:3:4:7-tetramethoxyphenanthrene-10-carboxylic acid which was 

 also synthesized. Similar stepwise oxidation of /.vodeaminocolchinol 

 methyl ether (III) gave 2:3: 4:7-tetramethoxy-9-phenanthraldehyde 

 (VII) , identical with a synthetic specimen. 



These results leave little room for doubt that deaminocolchinol 

 methyl ether and its wo-compound are correctly formulated. More- 

 over, Cook, Dickson, and Loudon--' Irdxe shown that the synthesized 



