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2,409,293
Patented Oct. 15, 1946
UNITED STATES PATENT orrlcsd
HORMONE INTERNIEDIATES AND PREP.
ARATION 0F SAlVlE
,
'
Russell Earl Marker, MexicoCity, Mexico, assign
or to Parke, Davis 8; Company, Detroit, Mich,
a corporation of Michigan
No Drawing. Original application June 30, 1941,
Serial No. 400,559., Divided and this applica
tion May 24, 1944, Serial No. 537,201
5 Claims. (C1, 260-—397.4)
2
other substance containing reactive hydrogen,’
for example, the combination of sodium metal
and ethyl alcohol, leads to the formation of 9.
20(00 -hydroxypregnane compound whichmay be
represented by the following partial formula,
This invention relates to the preparation of
certain hormone intermediates, and this applica
tion is a division of my copending application,
Serial No. 400,559, ?led June 30, 1941, now Patent
No. 2,352,648, issued July 4, 1944.
In my copending application, Serial No. 393,
667, ?led May 15, 1941, now Patent No. 2,352,852,
issued July 4, 1944, it is shown that steroidal
CH3
CH3
(11H . . . OHM)
sapogenins can be converted into a new class of
compounds which I designate as pseudo-sapogen
ins including pseudo-sapogenin eXo-acylates.
In my copending application, Serial No. 382,
Where the term 20-(a) -hydroxy occurs in this
451, ?led March 8, 1941, now Patent No. 2,352,850,
speci?cation, it will be understood that this term
issued July 4, 1944, it is shown that diosgenin
refers to one of the two epimers theoretically
may be converted into pseudo-diosgenin diace 15 possible. See further R. E. Marker et al., J. Am.
tate.
Chem. Soc., 59, 2291 (1937).
In the copending application of Marker, Crooks
My invention may be illustrated by the follow
& Wittle, Serial No. 393,666, ?led May 15, 1941,
ing examples.
now Patent No. 2,352,851, issued July 4, 1944,
(a) Diosgenin is treated as set forth‘ more
there is described the oxidation of pseudo-sapo 20 fully in my copending Patent No. 2,352,850 for
genin exo-acylates to give a new class of esters
six to ?fteen hours with acetic anhydride at
designated 20-keto-16-(e-acyloxy-isocaprooxy)
200° 0., thereby forming pseudo-diosgenin di
acetate. After crystallization from methanol,
pregnane compounds represented by the partial
formula
the pseudo-diosgenin diacetate has a melting
'
25 point of 97-100" 0.
CHa
CH2
(b) Pseudo-diosgenin diacetate is oxidized
with chromic anhydride in acetic acid at 28° 0.,
=0
as set forth more fully in the copending Patent
No. 2,352,851. Thus there is obtained the corre
30
sponding 20 - keto - l6 - (6-acyloxy-isocaprooxy) -
pregnane compound of melting point 85-86“ C.
This compound is believed to have the structure,
In my Patent No. 2,352,648, I have described
and claimed a process comprising the reduction
ll
CHz-C-o
by non-hydrolytic reagents of a 20-keto-16-(6
acyloxy-isocaprooxy)-pregnane compounds and
subsequent treatment with a hydrolytic agent to
obtain a 20(5), l?-dihydroxypregnane compound.
According to the invention in this divisional
application, instead of using non-hydrolytic re
ducing agents, I employ reducing agents which
also have a hydrolytic action thereby completely
removing the group at C16.
Thus, reduction of a 20-keto-16-(6-acyloxy
isocaprooxy) -pregnane compound with the com
and it may be designated as As-pregnenediol
45 3(5) ,16 - one - 20 3 - acetate-l6-(a-acetoxy) -iso
caproate.
,
(c) To 2 g. of the product, melting point 85-86°
0., designated as A5-pregnenediol-3-(B) ,16-one
20 3-acetate-16-(6-acetoxy) -isocaproate, in 200
cc. of dry isopropyl alcohol is added 15 g. of so
dium in small pieces. The mixture is re?uxed for
about an hour or until all the sodium has been dis
solved. Thereupon water is added and the mix
ture extracted well with ether. vThe ethereal
layer is washed with water and then the ether is
bination of an alkali metal and. an alcohol or 55
2,409,293
3
removed on a steam bath. The residue is crystal
consisting of hydroxyl and groups hydrolyzable
lized from dilute acetone and from dilute meth
to hydroxyl, to the action of an alkali metal in
combination with an alcohol reactive with said
anol and thus yields A5-pregnenedio1-3-(?) ,20
(a) of melting point 171-176“ C.
alkali metal to form nascent hydrogen, thereby
The structure of the above product is shown by 5 producing a steroid of the formula
the fact that it may :be hydrogenated in the pres
CH:
ence of glacial acetic acid and a platinum oxide
CH:
OH:
catalyst to yield allo-pregnanediol-B-(?),ZO-(u)
of melting point 214-216? C.
The above examples are intended to illustrate 10
but not to limit the scope of my invention. Other
modes of employing my processapparent to those
skilled in the art after this disclosure, are, in
tended to fall within the scope of my invention
and accordingly I wish to limit the scope of my
invention only as indicated in the appended
claims.
What I claim as my invention is:
1. Process for preparing hydroxy-pregnane de
rivatives which comprise subjecting a steroid hav
ing in ring D the structure
20
_/
/\
“bx/l
\)
'ILA
3. Process for preparing hydroxy-pregnane de
rivatives which comprises subjecting a steroid
of the formula
CH3
CH3
CH3
I o
C=
CH3
H . . . OH(c<)
CH:
(I)
\ ___/
OH:
l- H:- O ~acy l
0 (JJ CH2- CH2- (EHO
———
D I
25
CH:
YL/V
to the action of an alkali metal in combination
with an alcohol reactive with said alkali metal to
hydroxyl and groups hydrolyzable to hydroxyl,
form nascent hydrogen, thereby producing a ster
oid having in ring D the structure
to‘ the action of an alkali metal in combination
with an alcohol reactive With said alkali metal
where Y is a member of the class consisting of
to form nascent hydrogen, thereby producing a
steroid of the formula
CH:
cm.
on . . . one!)
35
CH:
Dl
H . . . OHM)
/ \/
2. Process for preparing hydroxy-pregnane de- 40
rlvatives which comprises subjecting a steroid of
the formula
CH3
CH:
CH3
=0
..
/
I (H)
4o
CH1:
‘
5
6
HA
where 71A represents 11 carbon-to-carbon double
bonds between C5 and C5, 11 having one of the
values 0 and 1, and Y is a member of the class
I
/\
V
How
4. Process for preparing A5-pregnenediol—3
(/3),20-(u) which comprises subjecting Ali-preg
nenediol - 3-(5) ,16-one-20 3-acetate-16-(6-acet
oxy)-isocaproate to the action of a alkali metal
in combination with an alcohol reactive with said
alkali metal to form nascent hydrogen.
V-O-C-CHz-CHz-élH-CHz-O-ac?
Y
CHa
OH:
50
5. Process for preparing A5-pregnenediol-3
(,B),20—(a) which comprises subjecting A5-preg
nenediol - 3-(p),16-one-20 3-acetate-l6-(6-acet
oxy) -isocaproate to the action of sodium and iso
propyl alcohol.
RUSSELL EARL MARKER.
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