KONRAD BLOCK 



general by addition of a proton to the most strongly basic double 

 bond. In hydrocarbons of the squalene type this addition will 

 occur at the two terminal double bonds. The resulting carbon- 

 ium ion will be prone to cyclize 



and the cyclization product will be six-membered if the relative 

 position of the double bonds and their orientation are as shown 

 above. These prerequisites for the transformation of an acyclic 

 terpene to a cyclic product are not met by the arrangement of 

 the squalene chain in Robinson's scheme. 



For facilitating the more recent advances in the knowledge 

 of steroid biogenesis much credit must be given to Ruzicka and 

 Jeger (24) for their structural work on the steroid alcohol 

 lanosterol, which is a major component of wool fat. Hitherto 

 regarded as a triterpene because, like squalene, it contains 30 

 carbon atoms, lanosterol was shown to have in fact the same 

 tetracyclic ring system as the steroids and was identified as 

 a 4,4 ',14 trimethylcholestadienol (Figure 2). Lanosterol there- 

 fore constitutes the structural link between the triterpenes and 

 the steroids which had been foreshadowed by biogenetic con- 

 siderations. What distinguishes lanosterol structurally from 

 other triterpenes is its failure to obey the isoprene rule ; it cannot 

 be constructed formally from isoprene residues, though its 

 elementary composition suggests an origin from 5-carbon units. 

 On the other hand, as a sterol, lanosterol is atypical by virtue of 

 the three additional methyl groups which are attached to the 

 ring system. If lanosterol were to be included in a general 

 scheme of steroid biogenesis, then squalene should be its precur- 

 sor as it is for cholesterol. Yet a ring closure in line with scheme 

 A (Figure 2) is clearly incapable of rationalizing the position of 

 the branched methyl groups in lanosterol. Thus, apart from 

 considerations of the course of acid-catalyzed transformations in 

 the terpene field the structure of lanosterol also called for a re- 

 vision of Robinson's cyclization scheme. The alternative 



478 



