The preparation of 3α,12α-bisdimethylamino-5β-cholane
dimethiodide, 3α,12α-bisdimethylamino-5β-cholane
dimethiodide, 3α,12α- bisdimethylamino-24-nor-5β-cholanedimethiodide,
and 3α,12α- bisdimethylamino-24-nor-5β-cholanediethiodide,
from deoxycholic acid are described. During this work it was found that
attempted copper- quinoline decarboxylation of dehydrocholic acid gives rise to
lactol formation, and that what had previously been considered to be 3α,12α- dihydroxy-5β-cholane is a mixture of
this compound and 12α,24- dihydroxy-5β-cholane. Comparable
selectivity of attack by methanesulphonyl chloride and toluene-p-sulphonyl
chloride occurs with various polyhydric alcohols derived from bile acids, as
evidenced from the products of reduction of the sulphonates with lithium
aluminium hydride. With both 5α- and 5β-cholane derivatives, a C 3
equatorial hydroxyl group exhibits comparable reactivity to the terminal
primary hydroxyl group, generated from the bile acid carboxylic group, towards
both sulphonyl chlorides. With axial hydroxyl groups at C 7 and C 12,
toluene-p-sulphonate formation is much more difficult than methane- sulphonate
formation. Reduction by means of lithium aluminium hydride of equatorial
sulphonate esters at C 7 and C 12 gives rise to a methylene group, but the axial
sulphonates under the same conditions give the axial alcohol. The same clear
distinction between equatorial and axial sulphonate esters is not observed at C
3 and C 6, but 17α- methanesulphonyloxy-5α-androstane
gives 5α-androstane and the 17β- ester gives 17β-hydroxy-5α-androstane.
Reduction of 12-oximino groups in both 5α- and
5β-cholanes with sodium and ethanol, hydrogen in
the presence of a catalyst, or lithium aluminium hydride gives solely the
12α-amino compound.