318 Essays in Biochemistry 



alkaloids (Pelletier and Jacobs, Kupchan et al.). Veracevine, which 

 can be obtained from the latter by methanolysis, is transformed into 

 cevine under the conditions (vigorous alkaline hydrolysis) generally 

 used for liberating the alkamine moiety. Yet another isomer, cevage- 

 nine (Stoll and Seebeck) , is formed from veracevine on mild treatment 

 with alkali. Cevagenine differs from cevine and veracevine in that it 

 contains a ketonic carbonyl. These isomers are formulated by Barton 

 et al. as shown in XXXII, XXXIII, and XXV, and accordingly the 

 three known ester alkaloids, cevacine, veratridine, and cevadine, have 

 to be expressed as XXXIIa, b, and c, respectively. It would lead too 

 far afield to review here the evidence for the configurational assign- 

 ments for C-3, C-5, and C-9 in these isomers and for the asymmetric 

 centers in the remainder of the molecule. 



Genuine, a native alkamine which occurs in nine of the ester alka- 

 loids presently on record, is under the influence of alkali analogously 

 isomerized to the ketonic isogermine 21 and further to the non-ketonic 

 pseudogermine, 22 and before long evidence was at hand showing that 

 this behavior is referable to the presence of an isomerizable a-ketol 

 system similar to that of veracevine 23a but differing from it in that 

 the terminus of the hemiacetalic ether bridge is C-7 and not C-9. 23b 

 This was deduced from: (1) The finding that all three genuine isomers 

 form tetraacetates (which is possible only if the hydroxyl function 

 at that terminus is primary or secondary). (2) The fact that the 

 hemiacetalic ring is five-membered (formation of an aldehydo-y- 

 lactone on periodate oxidation of genuine (or pseudogermine) ace- 

 tonide. 23a (3) The exclusion of the alternative non-tertiary y-positions 

 1 and 19 for that hydroxyl function on the grounds that germine, like 

 cevine, can be degraded to the tetracarboxylic acid XXVIII which 

 carries no oxygen at these carbon atoms. Finally Kupchan and 

 Narayanan, 24 on the basis of additional but perhaps somewhat less 

 compelling evidence which cannot be given here in detail, came to 

 ascribe structures XXXI Va and b, respectively, to the aforementioned 

 germine acetonide aldehydo-y-lactone and its diacetate and thus to 

 formulate germine itself as XXXV. 



Although structural information on the other two tertiary alkamines 

 of this group, zygadenine and protoverine, is still scant, there can be 

 little doubt that they, too, conform with cevine in regard to the nature 

 of the skeleton and the presence of an isomerizable ketol system. 



Thus, except for what remains to be done on these two alkamines, 

 the task of the organic chemist in this field has been largely accom- 

 plished. With the coexistence in several species of two principal groups 



