118
Lours P. FIESRR AND SRINIVASA RAJAGOPAT.AN [CONTRIBUTION FROM THE CHEMICAL
Oxidation of Steroids. IV.
T.01. 7;
LABORATORY O F HARVARD UNIVERSITY]
Methyl A'(('')-Lithocholenate and Methyl 9a,l laOxidolithocholanate1B2
BY LOUISF. FIESER AND
SRINIVASA
This extension of previous of the reactions of 9,11-dehydro and 9,ll-oxido derivatives of cholanic acid and lithocholic acid was undertaken with the idea that a successful method of converting a 9,11-ethylene into an 11-keto derivative might be applied to intermediates obtainable from sources other than desoxycholic acid. The fact that no good method yet exists for the preparation of methyl Ag(ll)-lithocholenate (I) from desoxycholic acid thus is no matter for immediate concern. 'The unsaturated ester employed in the present work was prepared from 12-keto- Ag(")-lithocholenic acid or its 3-carbethoxy methyl ester20 by WONKishner reduction according to Huang-Minlon'O and esterification in over-all yield of about 50%. As is generally true of a,/?-unsaturated ketones, the Wolff-Kishner reaction in this instance6jggives a mixture of hg(L1)-lithocholenicacid, Ail-lithocholenic acid and lithocholic but a convenient method was found for isolation of the Ag(ll'-acidas the methyl ester. Methyl As(l~)-lithocholenate(I) proved to be completely resistant to N-bromosuccinimide in aqueous acetone or even in aqueous t-butanol. Stavely"a has reported that N-bromoacetamide in aqueous acetone converts the ?,-acetate of I into the bromohydrin, but we did not investigate the action of N-bromosuccinimide on this derivative. We previously reportedzhthat in aqueous acetone N -broinosuccinimide attacks the 5,6-double bond of cholesterol, and we have now found that methyl A"-lithocholenate reacts under the same conditions to give the llp,l2a-dibromide and the llp-hydroxy-12a-bromo derivative; the 3a-hydroxy compound thus reacts the way its 3-acetate reacts with N-bromoacetamide in aqueous t-butanol. The behavior of methyl A9(11)-lithocholenatethus affords further evidence of the inert character of the 9,11double bond. The resistance of the ester to oxidation a t the alcoholic function by N-bromosuccinimide in aqueous t-butanol is abnormal, since 3a-hydroxyl groups usually are oxidized.2c I t was therefore surprising to find that the corresponding oxide, lormulated as the 9a,1la-oxide (IT) on the basis of evidence to be reported later, is oxidized to a dehydro compound by even milder ( 1 ) l h i s work was supported i n p a r t b y grants from t h e Tj S. Public Health Service, t h e Rockefeller Foundatioii u n d Rcscarcli Corporation. ('2) Fieser and Rajagopalan, (a) P a r t I , 'l'irrs J u T : K N - ! I . , 71, 3935 949); (b) Part TI, ibid , 71, ,3938 ( l 9 4 i I l '
