Chemistry 171 



the liiuf ol writing', preliminar\ \v()rk in ihis diicdion is cnoaoing 

 nuuh attention.''^ "•'•' The colchicine striictme is novel chielly in re- 

 spect ol the two fused 7-nienibeie(.l rings ol its tricyclic svstcni. These 

 lings are retained in a coni]jound, C,.|Hj,;0;., which Rapoporl and 

 W^illianis-''^ prepared Ironi colchicine by a series ot hydrogenation 

 reactions. In this jjrodiict ring A ol colchicine is unaltered, but rings 

 B and C are fidly reduced and devoid ol substituent grouj^s. Syn- 

 thesis ol this conipoimd is potentially more simple, although also less 

 significant, than that ot colchicine itself. But even total synthesis of 

 the alkaloid, when achieved, is unlikelv to have more than academic 

 importance: synthetic colchicine will not soon pro\ ide an economic 

 replacement of the natmal product. Here another issue is joined, 

 for it may be possible from a study ot the alkaloid and its immediate 

 derivati\es to discern some pattern of atoms or groups, ^\•hich is as- 

 sociated ^vith colchicine's elfeci on mitosis. By incorporating this 

 molecidar pattern in simpler and more accessible compotuids it 

 would then be possible to search on a rational basis for synthetic 

 substitutes. Already several attemjits have been made to achieve this 

 end and some success has been claimed for compoimds modeled on 

 the earlier, partly erroneous formida of AV^indaus (see work by Lettre 

 discussed in Clhapter 1 7) . As woidd be exj^ected, tropolone deriva- 

 tives have been investigated for their effect on cell mitosis. For in- 

 stance, p-acetamidotropolone (XXV) — a compound possessing obvi- 

 ous structmal similarities to colchiceine — was examined, in Trades- 

 cnntia cells //; t'/t'c;, bv "\\\ida''" 'who records a strong^ radiomimetic 



NH.Ac 



v 



o 



OH 

 ( XXV ) 



acticju and regards the compound as a possible mtuagenic sul^stance. 

 Its effect, however, does not appear to be identical with that oi colchi- 

 cine. 



As an aid to biologital studies Raffauf, Farren, and UlKot''^ ha\e 

 jjrejjared C^^-labeled deiivatives of colchicine by metliylation ot col- 

 chiceine with labeled dia/omethane and by acet\lation of desacetyl- 

 colchicine with labeled acetyl chloride. 



