KONRAD BLOCH 



thought to be established by the successive or perhaps synchro- 

 nous passage through various carbionic forms without stabihza- 

 tion of any of the transition stages. The reaction sequence I 

 through VI (Figure 3) is that proposed by Ruzicka; on the 

 whole it follows the rules established in the acid-catalyzed 

 cyclization of terpenes and assumes lanosterol (XII, Figure 4) to 

 be the first stabilized product. In the slightly modified version 

 of the cyclization process proposed here (Figure 4) the conver- 

 sion of the intermediate VI to lanosterol is somewhat more de- 

 tailed and a stabilized intermediate (isoeuphol, IX) is postulated 

 at an earlier stage. This suggestion is based on the constitution 

 of euphol, another triterpenoid alcohol intermediate in structure 

 between the classical sterols and the triterpenes. Euphol 

 (XVI, Figure 4) has only recently been identified as an isomer 

 of lanosterol from which it differs by having the G13 methyl group 

 and the isooctyl side chain in the « configuration and the methyl 

 group at Ci4 in the j3 configuration (1,2). This configuration 

 imposes a strain on the molecule and explains the facile trans- 

 formation of euphol into the isomeric isoeuphol (IX) in the 

 presence of mineral acid (23). The isomerization involves a 

 shift of the double bond to ring D and transposition of the 

 methyl group at C^ to Cs and of the C13 methyl to Ch (reactions 

 IX, XIII to XVI). What is unique for the structure of isoeu- 

 phol and of particular interest for the present discussion is the 

 presence of the completed tetracyclic ring system of the steroids, 

 with retention of the two methyl groups (at Cs and C14) in 

 vicinal positions. This structural feature has not been en- 

 countered among naturally occurring steroids but is typical of 

 the pentacyclic triterpenes. If isoeuphol were a key inter- 

 mediate in the cyclization of squalene, euphol could be formed 

 biologically by reversal of the steps IX, XIII to XVI. Since the 

 configuration of the methyl group at Cg of isoeuphol is jS and of 

 the methyl at Ch a, the isomerization process would be expected 

 to involve two 1,2 methyl shifts (from Ch to C13 and from Cg to 

 Ch). Because of the particular stereochemical arrangement, 

 euphol is an unstable molecule and therefore the euphol- 



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