18cc-Olean-I 2-ene, which is in acid-catalysed equilibrium with olean-I 3(18)-ene (6-amyrene), has been converted in several steps into olean-I 2-ene (@-amyrene). Transformation of this hydrocarbon into its 11 a-hydroxyderivative and photolysis of the nitrite of the latter gave 11 a-hydroxy-I -0ximino-olean-I 2-ene. This oxime has been hydrolysed and further processed to furnish olean-I 2-en-1 -one. Several methods have been developed to change the 1 -ox0 into a 3-oxo-function and vice versa. Since olean-I 2-en-3-one has already been reduced to @-amyrin and olean-I 3(18)-ene has been synthesised, our work constitutes a synthesis of @-amyrin.Related studies on the photolysis of 11 @-hydroxyolean-12-ene nitrite and on the interrelationship of the 1and 3-oxo-groups in the lanostane series are also recorded. ~A M Y R I N(3P-hydroxyolean-12-ene) (V; R = OH) is the parent compound of the large p-amyrin group of pentacyclic triterpenoids. The elucidation of the constitution and stereochemistry of p-amyrin was, in its time, a classic piece of work; however, the synthesis of p-amyrin has not hitherto been reported. We felt that this synthesis would be of significance in its own right and would pose problems the solution of which might be of general interest.Since the pioneering investigations of Halsall and Thomas in the synthesis of pentacyclic triterpenoids, three successful syntheses of olean-13( 18)-ene (6-amyrene) (11), or its equivalent, have been Olean-13(18)-ene (11) and 18a-olean-12-ene (I) are in acidcatalysed equilibrium5 although the equilibrium is largely in favour of the more highly substituted olefin (11). Therefore if 18a-olean-12-ene (I) could be transformed into olean-12-ene (V; R = H) and the latter hydroxylated at C-3 in the p-configuration, a synthesis of pamyrin would result. We describe first the interconversion of the hydrocarbons.18a-Olean-12-ene was oxidised with chromic acid to

By using cell-free preparations of rat liver it was shown that the removal of the 14alpha-methyl group (C-32) of steroids containing either a delta7(8) or a delta8(9) double bond is attended exclusively by the formation of the corresponding 7,14- and 8,14-dienes respectively (structures of types III and VIII). Cumulative evidence from a variety of experimental approaches had led to the deduction that delta8(14)-steroids are not involved as intermediates on the major pathway of cholesterol biosynthesis. The metabolism of [32-3H]lanost-7-ene-3beta,32-diol (structure of type I) results in the formation of radioactive formic acid, no labelled formaldehyde being formed. By using appropriately labelled species of the compound (I) it was found that the release of formic acid and the formation of 4,4-dimethylcholesta-7,14-dien-3beta-ol (strurcture of type III) were closely linked processes, and that in the conversion of compound (I) into compound (III), 3-beta-hydroxylanost-7-en-32-al (II) is an obligatory intermediate. Both the conversion of lanost-7-ene-3beta,32-diol (I) into 3beta-hydroxylanost-7-en-32-al (II) and the further metabolism of the latter (II) to 4,4-dimethylcholesta-7,14-dien-3beta-ol (III) exhibited a requirement for NADPH and O2. This suggests that the oxidation of the 32-hydroxy group of compound (I) to the aldehyde group of compound (II) does not occur by the conventional alcohol dehydrogenase type of reaction, but may proceed by a novel mechanism involving the intermediacy of a gem-diol. A detailed overall pathway for the 14alpha-demethylation in cholesterol biosynthesis is considered, and proposals about the mechanism of individual steps in the pathway are made.

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It is shown that the removal of the 32-carbon atom in cholesterol biosynthesis occurs a t the oxidation state of an aldehyde resulting in the release of formic acid.