Organic Chemistry of Drug Synthesis. Volume 7

route from this point on is speculative as details are not readily accessible.
Reaction of this last literature intermediate ( 72 ) with methanesulfonyl
chloride would then lead to mesylate 73. This group could then be dis-
placed by sulfur on the fluorinated mercaptan ( 74 ). Controlled oxidation
of sulfur, for example, with periodate, would then lead to the correspond-
ing sulfone. Saponification of the ester groups at the 3 and 17 positions
would afford the estrogen antagonistfluverestant,( 75 ).^13 Note that this
specific compound is but one from a sizeable group of similarly substituted
estradiol derivatives that shows pure antagonist activity.

OAc

O

Br OSiCH 3

H 3 C tBu

Mg

OAc

O

Si

CH 3

CH (^3) tBu
68
69
70

1. H2. Ac+
   2 O
   OAc

O

71

1. CuBr2. NaOH 2


2. C 6 H 5 COCl

OAc

C 6 H 5 CO

72

OAc

C 6 H 5 CO

73

OH

HO

OH OAc

O

SO

CF 3

1. HS
   2. [O]

FF

3. OH–

75

CF 3

F F

74

OSO 2 CH 3

Synthesis of 19-norandrostanes, which carried a functionalized benzene
ring at the 11 position, led to the surprising discovery of compounds that
antagonized the action of progestins and glucocorticoids. One of those
compounds, mifepristone ( 76 ), more familiarly known as RU-486, was
quickly enveloped in controversy, as a result of its use for terminating preg-
nancy by nonsurgical means. A more recent example,asoprinosil( 84 )isa
more selective progesterone antagonist with reduced binding to glucocor-
ticoid receptors. Treatment of the diene 77 , a total synthesis derived 19-nor

32 ALICYCLIC COMPOUNDS