312 Essays in Biochemistry 



brought out in a reinvestigation of jervine, begun in 1950 in the labora- 

 tory of the writer, which definitely established the perhydrobenz- 

 fluorene structure XIII for this alkaloid. 



Much valuable information on jervine was already on hand from 

 the work of Jacobs with Craig, and with Sato. 8 Thus the evidence 

 adduced by these authors for a normal A/B ring system with a hydroxyl 

 group at C-3 and a 5,6 double bond was incontestable. The function 

 of the other two oxygen atoms present could not be ascertained by 

 simple chemical means. One of these was assumed to be oxidic and 

 to link C-23 in the piperidine ring (corresponding to the position of 

 the hydroxyl group in the dehydrogenation product III) to C-16 in 

 a normal ring D. The second inert oxygen atom was revealed as part 

 of an a,/?-unsaturated ketone grouping by the absorption spectrum 

 {Xmax, 250 nut). In view of the complete lack of reactivity towards 

 ketone reagents the ketonic carbonyl was placed in position 11 of a 

 normal six-membered ring C, and this in turn necessitated accom- 

 modating the conjugated double bond in 8, 9. 



That the latter proposition was incorrect became apparent from a 

 study of the ultraviolet characteristics of diacetyl-7-ketojervine and 

 its 5,6-dihydro derivative, 10 which showed that the new a, ^-unsaturated 

 ketone system created in the former compound by the introduction of 

 the 7-keto group could not be contiguous with that pre-existing in 

 jervine, and hence that ring C, if containing the unreactive keto group, 

 could not be normally constituted. In the further pursuit of the 

 problem the use of acetolyzing agents proved to be decisive. Thus, 

 treatment of jervine with boiling acetic anhydride and zinc chloride 

 yielded a nitrogen-free compound, C2.3H30O3, which contained the un- 

 reactive keto group as part of a dienone system. Its structure XIV 

 followed in essence from its oxidative degradation to acetaldehyde and 

 the en-l,4-dione XV and the alkali-induced aromatization of the latter 

 to the phenol XVIa, the absorption spectrum of which left no doubt 

 as to the presence of an a-indanone (or a-tetralone) system carrying 

 a phenolic hydroxyl group in the position indicated. The alternative 

 structures XVIb and XVIc could be excluded on the grounds that the 

 keto group which had survived the aromatization was completely un- 

 reactive to ketone reagents. 11 - 12 



When milder acetolytic conditions were employed, ring E was opened 

 without loss of the side chain and the reaction led through the inter- 

 mediate XVII to the indanone XVIII, the structure of which was 

 readily deducible from its spectrum and from the fact that on reduction 

 it formed a product showing benzenoid absorption. 11 ' 13 The presence 



