US2004034215A1PendingUtilityA1
5-Androsten-3beta-ol steroid intermediates and processes for their preparation
Priority: Aug 16, 2002Filed: Mar 21, 2003Published: Feb 19, 2004
Est. expiryAug 16, 2022(expired)· nominal 20-yr term from priority
C07J 21/003C07J 1/0011
41
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Claims
Abstract
The present invention provides 5-androsten-3β-ol steroid intermediates and processes for their preparation.
Claims
exact text as granted — not AI-modified1 . A 7β-hydroxy steroid of the formula (II)
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
where Z 1 -Z 2 is either a single bond, or a double bond.
2 . The 7β-hydroxy steroid (II) according to claim 1 where R 3 is H
3 . The 7β-hydroxy steroid (TI) according to claim 2 where R 3 is —C(O)—CH 3 .
4 . The 7β-hydroxy steroid (II) according to claim 1 where R 17 and R 18 form ═O.
5 . The 7β-hydroxy steroid (II) according to claim 1 where R 17 , R 18 , and the C17 carbon atom of the steroid backbone form the lactone ring.
6 . The 7β-hydroxy steroid (II) according to claim 5 where the lactone ring has the α and β stereochemistry shown in the formula
7 . The 7β-hydroxy steroid (II) according to claim 1 where the 7β-hydroxy steroid (II) is 5-androsten-3β,7β-diol-17-one.
8 . The 7β-hydroxy steroid (II) according to claim 1 where the 7β-hydroxy steroid (II) is 5,9(11)-androstadien-3β,7β-diol-17-one.
9 . A 11α-hydroxy steroid of the formula (III)
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
10 . The 11α-hydroxy steroid (III) according to claim 9 , wherein R 3 is H.
11 . The 11α-hydroxy steroid (III) according to claim 10 , wherein R 3 is —C(O)—CH 3 .
12 . The 11α-hydroxy steroid (III) according to claim 9 , wherein R 17 and R 18 form ═O.
13 . The 11α-hydroxy steroid (III) according to claim 9 , wherein R 17 , R 18 , and the C17 of the steroid backbone form the lactone ring.
14 . The 7β-hydroxy steroid (II) according to claim 13 , where the lactone ring has the α and β stereochemistry shown in the formula
15 . The 11α-hydroxy steroid (III) according to claim 9 , wherein the 11α-hydroxy steroid is 5-androsten-3β, 11α-diol-17-one.
16 . A 7β,11α-dihydroxy steroid of the formula (IV)
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
17 . The 7β,11α-dihydroxy steroid (IV) according to claim 16 , wherein R 3 is H.
18 . The 7β,11α-dihydroxy steroid (IV) according to claim 17 , wherein R 3 is —C(O)—CH 3 .
19 . The 7β,11α-dihydroxy steroid (IV) according to claim 16 , wherein R 17 and R 18 form ═O.
20 . The 7β,11α-dihydroxy steroid (IV) according to claim 16 , wherein R 17 , R 18 , and the C17 carbon atom of the steroid backbone form the lactone ring.
21 . The 7β-hydroxy steroid (II) according to claim 16 , where the lactone ring has the α and β stereochemistry shown in the formula
22 . The 7β,11α-dihydroxy steroid (IV) according to claim 16 , wherein the 7β,11α-dihydroxy steroid (IV) is 5-androsten-3β,7β,11α-triol-17-one.
23 . A process for the preparation of a 7β-hydroxy steroid of the formula (II)
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
where Z 1 -Z 2 is either a single bond, or a double bond,
the process comprising
(1) contacting a Δ 5 -steroid of formula (I)
where R 3 , R17, R 18 , and Z 1 -Z 2 are as defined above, with 7β-hydroxylase of Diplodia.
24 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 23 wherein R 3 is H.
25 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 24 wherein R 3 is —C(O)—CH 3 .
26 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 23 wherein R 17 and R 18 form ═O.
27 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 23 wherein R 17 , R 18 , and the C17 carbon atom of the steroid backbone form the lactone ring.
28 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 23 , where the lactone ring has the α and β stereochemistry shown in the formula
29 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 23 where the 7β-hydroxy steroid (II) is 5-androsten-3β,7β-diol-17-one.
30 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 23 where the 7β-hydroxy steroid (II) is 5,9(11)-androstadien-3β,7β-diol-17-one.
31 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 23 where the contacting is by fermentation, cell concentrate, whole cells or cell-free reaction.
32 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 31 where the contacting is by fermentation.
33 . The process for the preparation of a 7β-hydroxy steroid (II) according to claim 23 where the Diplodia is Diplodia gossypina.
34 . A process for the preparation of a 11α-hydroxy steroid of the formula (III)
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
the process comprising:
(1) contacting a Δ 5 -steroid of formula (I)
where R 3 , R 17 , and R 18 are as defined above and where Z 1 -Z 2 is a single bond with 11α-hydroxylase of Aspergillus.
35 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 34 wherein R 3 is H.
36 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 35 wherein R 3 is —C(O)—CH 3 .
37 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 34 where R 17 and R 18 form ═O.
38 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 34 wherein R 17 , R 18 , and the C17 carbon atom of the steroid backbone form the lactone ring.
39 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 34 wherein the lactone ring has the α and β stereochemistry shown in the formula
40 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 34 where the 11α-hydroxy steroid is 5-androsten-3β,11α-diol-17-one.
41 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 34 where the contacting is by fermentation, cell concentrate, whole cells or cell-free reaction.
42 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 41 wherein the contacting is by fermentation.
43 . The process for the preparation of a 11α-hydroxy steroid (III) according to claim 34 where the Aspergillus is Aspergillus ochraceus.
44 . A process for the preparation of a 7β,11α-dihydroxy steroid of the formula (IV)
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
the process comprising
(1) contacting a 7β-hydroxy steroid of formula (II)
where R 3 , R 17 , and R 18 are as defined above and where Z 1 -Z 2 is a single bond with 11α-hydroxylase of Aspergillus.
45 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 44 where R 3 is H.
46 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 45 where R 3 is —C(O)—CH 3 .
47 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 44 where R 17 and R 18 form ═O.
48 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 44 , wherein R 17 , R 18 , and the C17 carbon atom of the steroid backbone form the lactone ring.
49 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 48 wherein the lactone ring has the α and β stereochemistry shown in the formula
50 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 48 where the 7β,11α-dihydroxy steroid (IV) is 5-androsten-3β,7β,11α-triol-17-one.
51 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 48 where the contacting is by fermentation, cell concentrate, whole cells or cell-free reaction.
52 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 51 where the contacting is by fermentation.
53 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 48 where the Aspergillus is Aspergillus ochraceus.
54 . A process for the preparation of a 7β,11α-dihydroxy steroid of the formula (IV)
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
the process comprising
(1) contacting a Δ 5 -steroid of formula (I)
where R 3 , R 18 , and R 17 are as defined above and where Z 1 -Z 2 is a single bond with 7β-hydroxylase of Diplodia to produce a 7β-hydroxy steroid of formula (II)
where R 3 , R 17 , and R 18 are as defined above and where Z 1 -Z 2 is a single bond; and
(2) contacting the 7β-hydroxy steroid (II) of step (1) with 11α-hydroxylase of Aspergillus.
55 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 54 where R 3 is H.
56 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 55 where R 3 is —C(O)—CH 3 .
57 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 54 where R 17 and R 18 form ═O.
58 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 54 where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form the lactone ring.
59 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 54 wherein the lactone ring has the α and β stereochemistry shown in the formula
60 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 54 where the 7β,11α-dihydroxy steroid (IV) is 5-androsten-3β,7β,11α-triol-17-one.
61 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 54 where the contacting is by fermentation, cell concentrate, whole cells or cell-free reaction.
62 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 61 where the contacting is by fermentation.
63 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 61 where the Diplodia is Diplodia gossypina.
64 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 61 where the Aspergillus is Aspergillus ochraceus.
65 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 54 where the 7β-hydroxy steroid (II) of step (1) is not isolated prior to the contacting of step (2).
66 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 54 where the 7β-hydroxy steroid (II) of step (1) is isolated prior to the contacting of step (2).
67 . A process for the preparation of a 7β,11α-dihydroxy steroid of the formula (IV)
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
the process comprising
(1) contacting a Δ 5 -steroid of formula
where R 3 , R 18 , and R 17 are as defined above and where Z 1 -Z 2 is a single bond with the 7β,11α-hydroxylase(s) of Absidia.
68 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 67 where R 3 is H.
69 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 68 where R 3 is —C(O)—CH 3 .
70 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 67 where R 17 and R 18 form ═O.
71 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 67 where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form the lactone ring.
72 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 67 wherein the lactone ring has the α and β stereochemistry shown in the formula
73 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 67 where the 7β,11α-dihydroxy steroid (IV) is 5-androsten-3β,7β,11α-triol-17-one.
74 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 67 where the contacting is by fermentation, cell concentrate, whole cells or cell-free reaction.
75 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 74 where the contacting is by fermentation.
76 . The process for the preparation of a 7β,11α-dihydroxy steroid (IV) according to claim 67 where the Absidia is Absidia coerulea.
77 . A process for the preparation of a 5, 9(11)-androstadien of formula I
where
R 3 is:
(1) —H;
(2) —CO—R 4
where R 4 is H or C 1 -C 5 alkyl;
where R 17 and R 18 together form ═O or
where R 17 and R 18 together with the C17 carbon atom of the steroid backbone to which they are bound form a lactone ring of the formula
and where Z 1 -Z 2 is a double bond, the process comprising:
(1) providing a compound of the formula (III)
where R 3 , R 17 , and R 18 are as defined above; and
(2) eliminating the 11α hydroxyl group to form the double bond between Z 1 and Z 2 (formula I).
78 . The process of claim 77 , wherein the step of providing the compound of formula III includes contacting a Δ 5 -steroid of formula (I)
where R 3 , R 17 , and R 18 are as defined above and where Z 1 -Z 2 is a single bond with 11α-hydroxylase of Aspergillus.Join the waitlist — get patent alerts
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