long been indicated for treating asthma. It has recently been found
that the acetal containing cylcohexane carboxaldehyde penetrates further
into the small airways. The first step in this brief sequence comprises
reaction of the syn diol ( 96 ) with isobutyric anhydride to afford the
triply esterified intermediate 97. Reaction of this compound with cylco-
hexane carboxaldehyde in aprotic solvent in the presence of acid leads
to formation of the acetal by a transesterification-like sequence. The
presence of the very bulky alkyl groups on the esters favors formation
of that isomer of the acetal in which the cyclohexane is oriented away
from the face of the steroid. The product ( 98 ) thus predominantly
comprises the desired isomer. Saponication of the remaining ester at 17
followed by separation from the small amount of epimeric acetal then
affordscicledesonide( 99 ).^18
OHOOOHOH
OH96CH 3
CH 3 2 O
OHOOOO
O97OOOOHOOOO
OO98OHOOOHO
O99OH–
SeparateOReplacement of carbon 4 in androstane by nitrogen leads to androgen
antagonists. These drugs have proven useful for treating a condition
marked by excess androgen or sensitivity there to such a benign prostatic
hypertrophy and even hair loss. Earlier examples are covered in Volumes 5
and 6 of this series. Synthesis of the most recent example starts by for-
mation of the amide between steroid carboxylic acid 100 and 1,4-
bis(trifluoromethylaniline) ( 101 ) via the acid chloride. Ring A is then
36 ALICYCLIC COMPOUNDS