KONRAD BLOCH 



already been discussed at some length. Much less can be said 

 at present about the further transformations of lanosterol, 

 notably the demethylation to the more abundant sterols which 

 have 27 carbon atoms. Compounds with either 1 or 2 fewer 

 methyl groups than lanosterol have to date not been encountered 

 in nature, and hence no clues exist to indicate the order in 

 which the 3 methyl substituents are eliminated. That oxida- 

 tion precedes the removal of the branched methyl groups appears 

 likely from the structure of the numerous cyclic terpenes in 

 which the 4,4' or 14 methyl groups are replaced by either 

 CHaOHor COOH: 



H3G CH2OH H3C COOH 



In the event that methyl elimination occurs by way of carboxylic 

 acid derivatives the introduction of keto groups j8 to, or of double 

 bonds j3,y to the carboxyl group would greatly facilitate decarbox- 

 ylation reactions. Since in lanosterol the 8,9 double bond is 

 located in /3,7 position with respect to the methyl group at Ch, 

 the demethylation process may well be initiated by oxidation of 

 the substituent at Cu (Figure 6). The resulting fi,y unsaturated 

 acid would then be susceptible to decarboxylation. Alterna- 

 tively, the 8,9 double bond could first shift to the 7,8 position as 

 it does in the acid-catalyzed isomerization of lanosterol. 



There is the second possibility that agnosterol, which is 

 A7,9,24 lanostatrienol and accompanies lanosterol in small 

 amounts in wool fat, is an intermediate in these conversions. 

 The diene system of agnosterol would tend to prevent a migra- 

 tion of the 7,8 double bond to the a,^ position, a shift which in 

 chemical systems at least accompanies the decarboxylation of 

 j8,7 unsaturated acids. Next, to facilitate the removal of the 

 gem-dimethyl grouping in ring A, a displacement of the double 

 bond to the 5,6 position may be visualized, and for this reac- 

 tion an enzymatic precedent may exist in the biological conversion 



486 



