Hydrogenation of a tetrasubstituted double bond: Synthesis of 5-methyl-19-nor-5β-pregnanes

Article abstract of DOI:10.1135/cccc19981549

Reduction of C=C and/or C=O bonds in 5-methyl-19-nor-5β-pregn-9-ene-3,20-dione (1) leads to saturated and unsaturated ketones and hydroxy ketones. The C=C reduction affords mainly 9β,10β and 9α,10β dihydro products. Reaction conditions of partial esterifi

Full text of DOI:10.1135/cccc19981549

On Steroids
1549
HYDROGENATION OF A TETRASUBSTITUTED DOUBLE BOND:
SYNTHESIS OF 5-METHYL-19-NOR-5β-PREGNANES*
1
2
Alexander KASAL , Jiri POLMAN and Milos BUDESINSKY
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
166 10 Prague 6, Czech Republic; e-mail: 1 kasal@marilyn.uochb.cas.cz,
2 budesinsky@uochb.cas.cz
Received April 6, 1998
Accepted June 19, 1998
Dedicated to Dr Jan Fajkos on the occasion of his 75th birthday.
Reduction of C=C and/or C=O bonds in 5-methyl-19-nor-5β-pregn-9-ene-3,20-dione (1) leads to
saturated and unsaturated ketones and hydroxy ketones. The C=C reduction affords mainly 9β,10β
and 9α,10β dihydro products. Reaction conditions of partial esterification, hydrolysis and oxidation
were elaborated. Several analogues were prepared for the testing of gestagenic and neurosteroidal
activities.
1
Key words: Westphalen rearrangement; Partial acetylation; Partial oxidation; Partial hydrolysis; H NMR
spectroscopy; Hydrogenolysis; Configuration; Steroids.
In our search for new analogues of steroid hormones2,3, we prepared 5-methyl-19-nor-
5β-pregn-9-en-3,20-dione4 (1) which turned out to cause abortion in rats5 and inhibited
fat deposition in the breast6. Here we deal with further modification of this compound,
consisting in the saturation of double bonds of the active compound which modifies the
overall conformation of the molecule and/or changes its functional groups.
Platinum-catalyzed hydrogenation of the tetrasubstituted ∆9-double bond was first
carried out by Grob7, who was the first to discover an apparent trans addition of hy-
drogen at the ∆9-double bond and to explain that this resistant double bond is first
isomerized by contact with the catalyst and only then hydrogenated. Snatzke8 found a
directing role in the hydrogenation of substituents in the position 6β and recently we
found9 that in the absence of 6β-substituents, a 3β-hydroxy group controls the stereo-
chemistry of the hydrogenation.
* Part CCCXCIX in the series On Steroids; Part CCCXCVIII see ref.1
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1550
Kasal, Polman, Budesinsky:
The resistance of the ∆9-double bond to saturation was manifested in the hydrogena-
tion of diketone 1 (Scheme 1) – under conditions of forced hydrogenation (acetic acid,
excess of the Adams catalyst, prolonged treatment), reductive deoxygenation of an oxo
group competed with the C=C saturation10,11 – in addition of dihydro derivative 2 and
O
O
O
H
H
(i)
+
H
H
O
O
6
1
2, 9α,10β
3, 9α,10α
4, 9β,10α
5, 9β,10β
(ii)
(iii)
HO
H
HO
H
HO H
H
H
H
H
H
H
HO
HO
17
18
19
(i) 1. H -Pt/AcOH, 2. Jones reagent/acetone; (ii) H -Pt/AcOH; (iii) Jones reagent/acetone
2
2
SCHEME 1
an intractable mixture of its isomers 3, 4 and 5, 3-deoxy compound 6 was formed
(23%). The given structures were confirmed by correlation with samples prepared as
follows: 6β-chloro derivative 7 (ref.12, Scheme 2) was treated with tributylstannane to
yield compound 8. Its hydrogenation under the same conditions afforded a mixture of
perhydro derivatives that was re-oxidized to a mixture of acetoxy ketones and hydro-
lyzed. A lipophilic fraction of the mixture (chromatography on silica gel) was a mixture
of two hydroxy ketones 9, 10 with a hydroxy group in an axial position. Its more
abundant component 9 was isolated by crystallization of the mixture: the 9α,10β struc-
ture assignment is based on a parallel with the recently studied hydrogenation of an-
drostane homologues9 leading to compounds 11, 12, 13 and 14 (see Table I).
The two most polar isomers 15 and 16 exhibited characteristics of the expected
9β,10β-dihydro derivative 15, i.e. a broad signal (a triplet of triplets) of the H-3α which
is axial in the 9β,10β-isomer only. Both isomers 15 and 16, however, differ in their 1H NMR
spectra: an H-17 signal at δ 2.56 is a triplet in the more lipophilic isomer 15 and a
doublet of doublets (δ 2.83) in the more polar one (16). Chemical shift of H-18 signals
of the two compounds also differ significantly (δ 0.62 and δ 0.92, respectively). The
given patterns correspond to C-17 isomers which was proved by circular dichroism: CD
curves of the isomers differ in a way expected of 17α- and 17β-pregnan-20-ones13.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

On Steroids
1551
O
O
H
(iii)
H
RO
RO
9, 9α,10β, R = H
10, 9β,10α, R = H
15, 9β,10β, R = H
43, 9β,10β, R = Ac
44, 9α,10β, R = Ac
X
7, R = Ac, X = Cl
8, R = Ac, X = H
41, R = H, X = H
(i)
(ii)
O
O
H
H
11, 9α,10β
12, 9β,10α
13, 9α,10α
14, 9β,10β
H
H
HO
HO
16
(i) tributylstannane/benzene; (ii) MeONa, MeOH; (iii) 1. H -Pt/AcOH, 2. Jones reagent/acetone
2
SCHEME 2
TABLE I
1H NMR spectra, chemical shifts (δ-scale) as criteria for differentiation between 9,10-isomers
Compound
9,10-Configuration
H-3
C(5)-Me
13
9α,10α
4.07 ma
1.29 s
11
9
9α,10β
9α,10β
9α,10β
4.16 ma
4.16 ma
4.16 ma
1.22 s
1.20 s
1.19 s
31
12
10
28
9β,10α
9β,10α
9β,10α
4.11 ma
4.11 ma
4.11 ma
1.12 s
1.18 s
1.20 s
14
30
15
17
9β,10β
9β,10β
9β,10β
9β,10β
3.71 ttb
3.72 ttb
3.73 ttb
3.73 ttb
1.04 s
1.01 s
1.02 s
1.01 s
a
b
W = 17.5 Hz. J(3α,2β) = J(3α,4β) = 11.6 Hz and J(2α,3α) = J(3α,4α) = 4.1 Hz.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1552
Kasal, Polman, Budesinsky:
Compound 15 was oxidized to the above diketone 5, diketone 5 was hydrogenated to
afford two diols 17 and 18 (Scheme 1) and alcohol 19 which could be oxidized to the
monoketone 6: this correlation confirms the 9β,10β-configuration in compounds 5 and 6.
Other analogues of diketone 1 were prepared from (20R)-pregn-5-ene-3β,20-diyl
dibenzoate (20, Scheme 3) as follows: a buffered solution of peroxyacetic acid con-
verted olefin 20 into a mixture of epoxides which were hydrated to 5,6-diol 21 (an
BzO
BzO
H
H
BzO
H
(i)
(ii)
BzO
BzO
(iii)
BzO
HO
OR
OR
20
21, R = H
22, R = Ac
23, R = Ac
25, R = H
(iv)
2
H
BzO
H
R O
2
H
R O
H
(vi)
(v)
H
1
BzO
R O
1
R O
O
24
1
2
1
2
17, 9β, 10β, R = R = H
26, R = H, R = H
1
2
1
2
27, 9α, 10β, R = R = H
29, R = H, R = Ac
1
2
1
2
28, 9β, 10α, R =R = H
36, R = Ac, R = H
1
2
1
2
30, 9β, 10β, R = H, R = Ac
46, R = Ac, R = Ac
(iv)
1
2
31, 9α, 10β, R = H, R = Ac
1
2
32, 9β, 10α, R = H, R = Ac
1
2
33, 9α, 10β, R = Ac, R = Ac
(vii)
1
2
39, 9β, 10β, R =Ac, R = H
RO
H
RO
H
1
2
40, 9β, 10β, R = Ac, R = Ac
H
H
H
O
O
Bz = benzoyl
37, R = Ac
38, R = H
34, 9α, R = H
35, 9α, R = Ac
42, 9β, R = Ac
45, 9β, R = H
(i) 1. AcOOH/CHCl ; 2. HClO /dioxane,acetone; (ii) H SO , Ac O; (iii) HCl/CHCl , MeOH;
3
4
2
4
2
3
o
(iv) Jones reagent/acetone; (v) N H .H O, KOH/diethyleneglycol, 200 C; (vi) H -Pt/AcOH
2
4
2
2
o
(vii) Jones reagent/acetone, -65 C
SCHEME 3
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

On Steroids
1553
unbuffered solution of peroxyacetic acid yielded a mixture of compound 21 and its
acetate 22). Acid catalyzed dehydration of the diol produced a Westphalen-type pro-
1
duct 23 (for H NMR data see Table II). Deoxygenation in the position 6 was carried
out by the Huang–Minlon reduction9 of ketone 24 prepared in a routine way via com-
pound 25. Hydrogenation of diol 26 proceeded without the above complications (deo-
xygenation of the 3-oxo group, equilibration of the pregnane side chain) to yield diols
17, 27 and 28. The 9β,10β-configuration of the first isomer (17) is again unambigu-
ously proved by the equatorial nature of the 3β-hydroxy group (H-3α is a triplet of
triplets, J = 11.3 and 4.1 Hz). In ascribing structures 27 and 28 to the isomers, the
signal of the 3α-proton was evaluated as above (see Table I). The 9α,10β compound 27
could be obtained by crystallization of the mixture.
Equally, we hydrogenated diol monoacetate 29 and obtained acetates 30 and 31 as
major products. Their isomer 32 was a more polar admixture of compound 31, crystal-
lization again proved sufficient to produce the pure major isomer 31.
Oxidation of diols 27 and 17 afforded diketones 2 and 5, respectively, which were
identical with the above obtained samples. The third diketone (4), formed in about 5%
yield, was not isolated, nevertheless, its NMR signals could be detected in the mother
liquor of compound 2.
The 3β hydroxy group in the 9α,10β-pregnane derivative 27 is axial and thus its
reactivity is lower than that of the C-20 hydroxyl. Compound 27 could therefore be
partially acetylated to yield 20-monoacetate 31 (60%) besides diacetate 33. Diol 27
could also be partially oxidized14 to yield mainly hydroxy ketone 34 (58%) which was
available also from 20-monoacetate 31 via acetoxy ketone 35.
A similar sequence was attempted in acetylation of unsaturated diol 26. Here, a
mixture of 20- and 3-monoacetates 29 and 36 could not be separated by chromato-
graphy: fortunately, the major product – the 20-acetoxy derivative 29 – could be ob-
tained by crystallization. Its oxidation (to 37) and hydrolysis afforded another analogue 38.
Reactivities of both hydroxy groups in the 9β,10β-diol 17 are similar and both mono-
acetates 39 and 30 were formed in comparable yields. However, reactivities of corre-
sponding ester groupings are so different that a 20-acetoxy derivative 30 was available
by partial hydrolysis of diacetate 40.
The monoesters prepared above were converted in physiologically interesting mono-
ketones 9, 15, 16, 34, 38, 41 and 45, and diketones 2 and 5 which will be used as
probes for finding structural requirements of the studied activity6. Some of the com-
pounds (9, 15, 16) are interesting for their potential neurosteroidal activity15.
In summary, hydrogenation of ∆9-olefins is best carried out with diol 26 or its ester
29 and yields mostly 9β,10β- and 9α,10β-dihydro products. For differentiation between
identical groups in positions 3 and 20, partial oxidation of diols (e.g. 17, 26, 27), partial
acylation of diols (e.g. 17, 26, 27) and partial hydrolysis of diesters (e.g. 40, 46) turned
out to be the most useful.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1554
Kasal, Polman, Budesinsky:
TABLE II
Characteristic parameters of 1H NMR spectra, chemical shifts in ppm (δ-scale), coupling constants
(J) and width of multiplets (W) in Hz
Com-
pound
H-3
H-20a C5-Me C13-Me C20-Me
Other signals
1
2
–
–
–
–
1.02 s 0.75 s 2.13 s
0.95 s 0.65 s 2.13 s H-4β: 2.72 d (J = 14.3);
H-17: 2.56 t (J = 8.9)
4
5
6
8
–
–
–
–
–
0.97 s 0.62 s 2.12 s
–
–
1.10 s 0.64 s 2.11 s H-17: 2.54 t (J = 8.9)
0.97 s 0.61 s 2.11 s H-17: 2.57 t (J = 8.9)
5.09 mb
1.18 s 0.74 s 2.11 s OAc: 2.07 s;
H-17: 2.57 t (J = 8.9)
9
10
15
16
17
18
19
21
4.16 mb
4.11 mb
3.73 ttc
3.55 ttc
–
–
–
–
1.20 s 0.61 s 2.11 s H-17: 2.52 t (J = 8.9)
1.18 s 0.64 s 2.13 s H-17: 2.61 t (J = 8.9)
1.02 s 0.62 s 2.11 s H-17: 2.56 t (J = 8.9)
0.99 s 0.92 s 2.11 s H-17: 2.83 dd (J = 8.2 and 2.4)
3.73 ttc 3.73 dq 1.01 s 0.76 s 1.14 d
4.07 mb 3.74 dq 0.96 s 0.77 s 1.13 d
–
3.75 dq 0.95 s 0.76 s 1.13 d
5.40 md 5.12 dq
–
0.69 s 1.27 d C10-Me: 1.20 s; H-6α: 3.56 m (W = 16);
Bz: 8.05 m (2 H), 7.48 m (3 H)
22
23
5.38 md 5.16 dq
–
0.70 s 1.27 d C10-Me: 1.16 s; H-6α: 4.71 m (W = 16);
OAc: 2.07 s; Bz: 8.05 m (2 H), 7.48 m (3 H)
5.38 mb 5.17 dq 1.32 s 0.82 s 1.27 d H-6α: 4.81 dd (J = 11.6 and 4.0);
OAc: 2.05 s; Bz: 8.05 m (2 H), 7.48 m (3 H)
24
25
5.42 mb 5.17 dq 1.47 s 0.80 s 1.28 d Bz: 8.05 m (2 H), 7.48 m (3 H)
5.38 mb 5.17 dq 1.25 s 0.82 s 1.27 d H-6α: 3.59 m (W = 30);
Bz: 8.05 m (2 H), 7.48 m (3 H)
26
27
28
29
30
4.14 mb 3.77 dq 1.27 s 0.90 s 1.15 d
4.15 mb 3.74 dq 1.20 s 0.75 s 1.14 s
4.11 mb 3.74 dq 1.20 s 0.76 s 1.14 d
4.16 mb 4.86 dq 1.25 s 0.75 s 1.14 d OAc: 2.02 s
3.72 ttc 4.86 dq 1.01 s 0.64 s 1.15 d OAc: 2.01 s
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

On Steroids
1555
TABLE II
(Continued)
Com-
pound
H-3
H-20a C5-Me C13-Me C20-Me
Other signals
31
33
34
35
36
37
38
39
40
41
42
43
44
45
46
4.16 mb 4.84 dq 1.19 s 0.63 s 1.15 d OAc: 2.02 s
5.08 mb 4.84 dq 1.10 s 0.63 s 1.15 d 2 × OAc: 2.01 s, 2.04 s
–
–
3.75 dq 0.94 s 0.71 s 1.15 d H-4β: 2.73 d (J = 14.3)
4.86 dq 0.94 s 0.66 s 1.16 d H-4β: 2.72 d (J = 14.3); OAc: 2.03 s
5.09 mb 3.77 dq 1.27 s 0.90 s 1.16 d OAc: 2.08 s
–
–
4.88 dq 1.01 s 0.77 s 1.18 d OAc: 2.03 s
3.76 dq 1.01 s 0.89 s 1.15 d
4.82 ttc 3.74 dq 1.02 s 0.76 s 1.14 d OAc: 2.02 s
4.84 ttc 4.84 dq 1.02 s 0.64 s 1.16 d 2 × OAc: 2.01 s, 2.03 s
4.13 mb
–
1.26 s 0.73 s 2.11 s H-17: 2.52 t (J = 8.9)
–
4.86 dq 1.09 s 0.65 s 1.14 d OAc: 2.01 s
4.84 ttc
5.08 mb
–
–
–
1.04 s 0.63 s 2.12 s H-17: 2.57 t (J = 8.9); OAc: 2.03 s
1.09 s 0.61 s 2.12 s H-17: 2.55 t (J = 8.9); OAc: 2.04 s
3.74 dq 1.09 s 0.77 s 1.13 d
5.07 mb 4.86 dq 1.17 s 0.76 s 1.15 d 2 × OAc: 2.02 s, 2.06 s
a
b
c
J(17.20) = 10.1 and J(20,21) = 6.2; W = 17.5; J(3α,2β) = J(3α,4β) = 11.6 and J(2α,3α) =
d
J(3α,4α) = 4.1; W = 40.
EXPERIMENTAL
Melting points were determined on a micro melting point apparatus Boetius (Germany) and are un-
corrected. Analytical samples were dried over phosphorus pentoxide at 50 °C/100 Pa. Optical rota-
tions were measured in chloroform and [α]D values are given in 10–1 deg cm2 g–1. Circular dichroism
(Mark V apparatus) were measured in methanol. IR spectra of chloroform solutions (unless stated
1
otherwise) were recorded on a Bruker IFS 88 spectrometer. Wavenumbers are given in cm–1. H NMR
spectra of prepared compounds were measured on a Varian UNITY-200 (at 200 MHz) spectrometer
at 23 °C in deuteriochloroform with tetramethylsilane as internal standard. Chemical shifts are given
in ppm (δ-scale), coupling constants (J) and width of multiplets (W) in Hz. Mass spectra were re-
corded on a VG Analytical ZAB-EQ spectrometer (energy of ionizing electrons 70 eV, ion source
temperature 180–220 °C). HPLC analysis (isocratic chromatography in methanol water, 75/25 w/w)
was done on a Spectra-Physics chromatograph (detection at 294 nm) using a Tessek Separon SGX
C18 (10 µm, 4 × 250 mm) column. Thin-layer chromatography (TLC) was done on silica gel (ICN
Biochemicals). Preparative thin-layer chromatography (PLC) was carried out on 200 × 200 mm plates
coated with a 0.7 mm layer of the same material. For column chromatography silica gel 60–120 µm
was used. Whenever aqueous solutions of hydrochloric acid, potassium hydrogen carbonate and po-
tassium carbonate were used, their concentration was always 5%.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1556
Kasal, Polman, Budesinsky:
Hydrogenation of 5-Methyl-19-nor-5β-pregn-9-ene-3,20-dione (1)
Diketone 1 (250 mg, 0.79 mmol) was hydrogenated by stirring its solution in acetic acid (5 ml) with
the Adams catalyst (160 mg) in a hydrogen atmosphere at room temperature for 20 h. The catalyst
was filtered off and washed with acetic acid, the filtrate was evaporated in vacuum and the residue
was oxidised with Jones reagent14 under standard conditions. An excess reagent was reduced with a
few drops of methanol. The product was precipitated on addition of the potassium hydrogen carbo-
nate solution and extracted with ether. The extract was washed with water, dried over sodium sulfate
and evaporated. The residue was chromatographed on a column of silica gel (100 g) in ligroin and
ethyl acetate (9 : 1) to yield the following fractions.
Fraction A: 5-Methyl-19-nor-5β,9β-pregnan-20-one (6, 45 mg, 23%), m.p. 133–134 °C (meth-
anol), [α]D +64 (c 1.1). IR spectrum: 1 706 (C=O); 1 385, 1 377, 1 356 (CH3). Mass spectrum, m/z
(%): 302 (90), 287(15), 259 (33), 244 (31), 217 (100). For C21H34O (302.5) calculated: 83.38% C,
11.33% H; found: 83.43% C, 11.76% H.
Fraction B: A mixture of 9,10-isomers of 5-methyl-19-nor-5β-pregnane-3,20-dione (2, 4 and 5,
167 mg, 67%) consisting of compound 2 (58%, HPLC), 4 (14%) and 5 (15%). Crystallization from
methanol yielded 5-Methyl-19-nor-5β,9α,10β-pregnane-3,20-dione (2, 26 mg), m.p. 193–194 °C,
[α]D +119 (c 1.2). IR spectrum: 1 700 (C=O); 1 422 (CH2–CO). Mass spectrum (FAB), m/z (%): 317
(100), 299 (45), 283 (12), 273 (17), 255 (18) 315 (23). For C21H32O2 (316.5) calculated: 79.70% C,
10.19% H; found: 80.06% C, 10.00 %H.
Repeated chromatography of the mother liquor yielded 5-methyl-19-nor-5β,9β,10β-pregnane-3,20-
dione (5, 19 mg), m.p. 127–128 °C, [α]D +78 (c 1.0). Circular dichroism: ∆ε287 +3.38. IR spectrum:
1 703 (C=O); 1 419 (CH2–CO); 1 358, 1 165 (CH3). Mass spectrum (FAB), m/z (%): 317 (89), 299
(46), 273 (16), 255 (23), 215 (17). For C21H32O2 (316.5) calculated: 79.70% C, 10.19% H; found:
79.71% C, 10.13% H.
Hydrogenation of 5-Methyl-19-nor-5β,9β,10β-pregnane-3,20-dione (5)
Diketone 5 (70 mg, 0.22 mmol) was treated with hydrogen as in the preceding experiment. PLC of
the crude product (70 mg) yielded following fractions.
Fraction A: (20R)-5-methyl-19-nor-5β,9β,10β-pregnan-20-ol (19, 6 mg, 8%) which was oxidized
to ketone 6 (see below).
Fraction B: a mixture of acetoxy alcohols (5 mg, 6%).
Fraction C: (20R)-5-methyl-19-nor-5β,9β,10β-pregnane-3α,20-diol (18, 41 mg, 54%), m.p. 203–204 °C
(acetone–heptane), [α]D –15 (c 0.9). IR spectrum: 3 615, 3 268 (O–H); 1 092, 1 057, 1 034 (C–O).
Fraction D: (20R)-5-methyl-19-nor-5β,9β,10β-pregnane-3β,20-diol (17, 7 mg, 9%) identical with
the authentic sample.
5-Methyl-19-nor-5β,9β,10β-pregnan-20-one (6)
The above sample of compound 19 (6 mg, 0.02 mmol) was dissolved in acetone (1 ml) and treated
with the Jones reagent at room temperature. After 10 min, methanol was added and the mixture was
evaporated in vacuum. The residue was extracted with chloroform, the extract was concentrated and
applied onto a thin layer of silica gel which was developed with benzene–ether (1 : 1). The major
1
product (3.9 mg, 65%) was eluted with ether. Its IR and H NMR spectra were found identical with
compound 6 prepared by hydrogenation of diketone 1.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

On Steroids
5-Methyl-20-oxo-19-nor-5β-pregn-9-en-3β-yl Acetate (8)
1557
A solution of chloro derivative 7 (10.0 g, 24.45 mmol) in toluene (150 ml) was added to a boiling
solution of tributylstannane in benzene (1 M, 28 ml, 28 mmol). The solution was refluxed for 9 h,
cooled and evaporated in vacuum. The product was purified by chromatography on silica gel (500 g,
ligroin–ethyl acetate, 40 : 1). The major product is compound 8 (8.1 g, 89%) m.p. 93–94 °C (methanol),
[α]D +93 (c 1.0). IR spectrum: 1 725, 1 701 (C=O); 1 270, 1 248, 1 020 (OAc). For C23H34O3
(358.5) calculated: 77.05% C, 9.56% H; found: 77.16% C, 9.21% H.
3β-Hydroxy-5-methyl-19-nor-5β-pregn-9-en-20-one (41)
Acetate 8 (342 mg, 0.95 mmol) was hydrolysed in methanol (5 ml) with a solution of sodium methoxide
in methanol (0.87 M, 2 ml, 1.74 mmol) at ambient temperature under argon. After 3 days, acetic acid
was added (0.5 ml), the solution was concentrated in vacuum and mixed with brine (30 ml). The
precipitate was extracted with chloroform, the extract was washed with water, dried over sodium sulfate
and evaporated. Product (310 mg, 89%) crystallized from ether–methanol, m.p. 143–146 °C, [α]D
+122 (c 1.2). IR spectrum: 3 615, 3 482 (O–H); 1 698 (C=O); 1 642 (C=C). For C21H32O2 1.5
CH3OH (364.6) calculated: 74.13% C, 10.51% H; found: 74.24% C, 10.24% H.
Hydrogenation of 5-Methyl-20-oxo-19-nor-5β-pregn-9-en-3β-yl Acetate (8)
a) The Adams catalyst (150 mg) was added to a solution of compound 8 (231 mg, 0.64 mmol) in
acetic acid (7 ml) and ethanol (3 ml) under a hydrogen atmosphere and the mixture was stirred at 60 °C
for 24 h. After removal of the catalyst, the filtrate was evaporated in vacuum and oxidised by Jones
reagent in acetone at 20 °C. The product was isolated in a standard way and hydrolysed by heating
with potassium carbonate (500 mg) in aqueous methanol (80%, 12 ml) under argon at 65 °C. After 4 h,
the mixture was diluted with brine and the precipitate was extracted with chloroform, washed with
water, dried over sodium sulfate and evaporated. The residue was fractioned by PLC (benzene–ether,
3 : 1) to yield the following fractions.
Fraction A: a mixture of isomers of 3β-hydroxy-5-methyl-19-nor-5β-pregnan-20-one 9 and 10 (87 mg,
42%). Two crystallizations from heptane afforded pure 3β-hydroxy-5-methyl-19-nor-5β,9α,10β-preg-
nan-20-one (9, 42 mg, 20%), m.p. 147–149 °C, [α]D +98 (c 0.9). Circular dichroism: ∆ε287 +2.70.
For C21H34O2 (318.5) calculated: 79.19% C, 10.76% H; found: 78.92% C, 10.84% H.
Fraction B: 3β-hydroxy-5-methyl-19-nor-5β,9β,10β-pregnan-20-one (15, 103 mg, 50%), [α]D +69
(c 1.1). Circular dichroism: ∆ε287 +2.91. IR spectrum: 3 607, 3 463 (O–H); 1 698 (C=O); 1 066,
1 020 (C–O). For C21H34O2 (318.5) calculated: 79.19% C, 10.76% H; found: 79.08% C, 10.81% H.
Fraction C: 3β-hydroxy-5-methyl-19-nor-5β,9β,10β,17β-pregnan-20-one (16, 15 mg, 7%), m.p.
147–149 °C (heptane), [α]D –98 (c 0.8). Circular dichroism: ∆ε286 –2.24. IR spectrum: 3 619, 3 500
(O–H); 1 700 (C=O); 1 475, 1 389 (CH3). Mass spectrum (FAB), m/z (%): 319 (40), 301 (83), 283
(40), 257 (25), 214 (18), 81 (100). High resolution mass spectrum, m/z: for C21H35O2 calculated
319.263706, found 319.268089.
b) Compound 8 (660 mg, 1.84 mmol) was hydrogenated in acetic acid (15 ml) and ethanol (5 ml)
as above. Oxidation of the product was carried out as above. However hydrolysis with potassium
carbonate (1.5 g) in aqueous methanol (80%, 36 ml), was carried out under argon at room tempera-
ture. After 4 days, acetic acid (1 ml) was added and the solution was concentrated in vacuum. The
product was precipitated with brine and extracted with chloroform. After washing with water, the
solution was applied on a thin layer of silica gel (12 PLC plates) to yield following fractions.
Fraction A: compound 9 (131 mg, 22%).
Fraction B: compound 15 (204 mg, 35%).
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Kasal, Polman, Budesinsky:
Fraction C: 5-methyl-20-oxo-19-nor-5β,9α,10β-pregnan-3β-yl acetate (44, 96 mg, 15%), [α]D +84
(c 1.1). IR spectrum: 1 725, 1 701 (C=O); 1 264, 1 250, 1 020 (C–O). Mass spectrum (FAB), m/z (%):
361 (M+, 100), 283 (50), 257 (19), 241 (8), 215 (12). High resolution mass spectrum, m/z: for
C23H37O3 calculated 361.274270, found 361.265500.
5-Methyl-19-nor-5β,9β,10β-pregnane-3,20-dione (5)
a) Hydroxy ketone 15 (12 mg, 0.04 mmol) was oxidized with the Jones reagent as above. Product
(11 mg, 92%), purified by PLC, had IR and NMR spectra identical with compound 5 prepared by
hydrogenation of dione 1.
b) Diol 17 (65 mg, 0.20 mmol) was oxidized with the Jones reagent and purified as above. Dione
5 (59 mg, 92%) was identical with the product prepared sub a).
5-Methyl-19-nor-5β,9α,10β-pregnane-3,20-dione (2)
1
a) Hydroxy ketone 9 (4 mg, 0.001 mmol) was oxidized as above, product had H NMR spectrum
identical with that of compound 2.
b) On oxidation with the Jones reagent, diol 27 (3.5 mg, 0.001 mmol) afforded diketone 2 identi-
cal with the above sample.
(20R)-5,6β-Dihydroxy-5α-pregnane-3β,20-diyl 3,20-Dibenzoate (21)
a) A solution of diester 20 (64.4 g, 122.3 mmol) in chloroform (150 ml) was treated with diso-
dium hydrogen phosphate heptahydrate (50.0 g, 186.5 mmol) and peroxyacetic acid (22% solution in
water, 100 ml) under stirring at ambient temperature for 5 h. The aqueous layer was separated and
extracted with chloroform, the extract was washed with water, a potassium hydrogen carbonate solu-
tion and water, and evaporated in vacuum. The residue was dissolved in dioxane (650 ml) and
acetone (350 ml) and treated with perchloric acid (5%, 100 ml) under stirring at ambient temperature.
After 4 h, the mixture was concentrated in vacuum to a quarter of the original volume and diluted
with brine (500 ml). The precipitate was filtered off, washed with water and dissolved in chloroform.
The solution was washed with water, dried over sodium sulfate and evaporated. Compound 21 (59.1 g,
89%) crystallized from toluene, m.p. 237–239 °C, [α]D –49 (c 1.1). IR spectrum: 3 621, 3 595, 3 462
(O–H); 1 706 (C=O); 1 603, 1 451, 1 315, 1 177, 1 120, 1 070, 1 027 (arom.); 1 279 (C–O). For
C35H44O6 (560.7) calculated: 74.97% C, 7.91% H; found: 74.91% C, 7.86% H.
b) A solution of diester 20 (124 mg, 0.24 mmol) in chloroform (1 ml) and acetone (0.5 ml) was
treated with peroxyacetic acid (22% solution in water, 1.0 ml) and perchloric acid (72%, 0.25 ml,
1.79 mmol) under stirring at ambient temperature. After 18 h, the mixture was diluted with chloroform
and washed with water, a potassium hydrogen carbonate solution and water, dried and evaporated in
vacuum. Thin layer chromatography (3 PLC plates, benzene–ether, 3 : 1) yielded compound 21 (73 mg,
55%) and a lipophilic product, acetate 22 (29 mg, 20%). IR spectrum: 3 620, 3 478 (O–H); 1 729,
1 709 (C=O); 1 603, 1 452 (arom.); 1 279 (C–O, benzoate); 1 257 (C–O, acetate).
(20R)-5-Methyl-19-nor-5β-pregn-9-ene-3β,6β,20-triyl 6-Acetate 3,20-Dibenzoate (23)
Compound 21 (64.0 g, 114.1 mmol) was dried by distillation with toluene which was then evaporated.
Acetic anhydride (900 ml) was added and the mixture was heated until 100 ml of the distillate was
obtained. The solution was cooled to 20 °C and sulfuric acid (45 drops) was added under stirring.
The mixture was maintained at 30 °C for 30 min and then at 20 °C for 2 h. The solution was poured
onto brine with ice (6 l) under stirring. After 18 h, the precipitate was filtered off, washed with a
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

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1559
solution of potassium hydrogen carbonate and water. The crude product was dissolved in chloroform,
filtered through a column with silica gel (50 g), evaporated in vacuum and crystallised from a mix-
ture of dichloromethane and methanol. M.p. 234–235 °C (38.1 g, 57%), [α]D +146 (c 1.1). For
C37H44O6 (584.8) calculated: 76.00% C, 7.58% H; found: 75.92% C, 7.61% H.
(20R)-6β-Hydroxy-5-methyl-19-nor-5β-pregn-9-ene-3β,20-diyl 3,20-Dibenzoate (25)
A solution of acetate 23 (38.06 g, 65.1 mmol) in a mixture of chloroform (200 ml) and methanol (1 l)
was treated with hydrochloric acid (20 ml) at 40 °C. After 48 h, the solution was concentrated in
vacuum and diluted with brine (2 l). The precipitate was filtered off and washed with water. Com-
pound 25 crystallized from dichloromethane–heptane (29.1 g, 82%), m.p. 224–225 °C, [α]D +157 (c 1.1).
IR spectrum: 3 611, 3 512 (O–H); 1 705 (C=O); 1 602, 1 451, 1 315 (arom.); 1 045, 988 (C–O). For
C35H42O5 (542.7) calculated: 77.46% C, 7.80% H; found: 77.39% C, 7.71% H.
(20R)-5-Methyl-19-nor-6-oxo-5β-pregn-9-ene-3β,20-diyl 3,20-Dibenzoate (24)
A solution of diester 25 (23.3 g, 42.7 mmol) in a mixture of acetone (200 ml) and toluene (200 ml)
was treated with the Jones reagent at ambient temperature. After 50 min, the excess oxidant was
reduced by methanol. The precipitate was filtered off and the filtrate was poured into a potassium
hydrogen carbonate solution. The precipitate was extracted with ether, the extract was washed with
water, dried and evaporated. The residue crystallized from dichloromethane–methanol. M.p. of
ketone 24 (19.9 g, 86%) was 192–193 °C, [α]D +27 (c 1.2). IR spectrum: 1 709, 1 427 (CH2C=O);
1 603, 1 585, 1 491, 1 315, 1 117, 1 070, 1 002 (arom.); 1 279 (C–O). For C35H40O5 (540.7) calcu-
lated: 77.75% C, 7.46% H; found: 77.68% C, 7.42% H.
(20R)-5-Methyl-19-nor-5β-pregn-9-ene-3β,20-diol (26)
Ketone 24 (3.0 g, 5.55 mmol) was heated with potassium hydroxide (5.7 g, 101.6 mmol) and hydra-
zine hydrate (10.0 ml, 205.6 mmol) in diethylene glycol (100 ml). When the temperature reached 140 °C, a
reflux condenser was set in. After 1 h, the condenser was removed and the temperature was increased
to 200 °C. The mixture was kept for 8 h at this temperature, then it was cooled and poured onto ice
(300 g) with hydrochloric acid (15 ml). The precipitate of compound 26 (1.69 g, 95%) was filtered,
washed with water and dried. M.p. 160–161 °C (toluene), undepressed with an admixture of an auth-
entic sample4, [α]D +54 (c 1.0) (ref.4 records 168–170 °C, +27).
Partial Acetylation of (20R)-5-Methyl-19-nor-5β-pregn-9-ene-3β,20-diol (26)
Diol 26 (1.7 g, 5.33 mmol) was treated with acetic anhydride (7.0 ml, 74.0 mmol) in toluene (26 ml)
and pyridine (11 ml) at ambient temperature. After 2 h, methanol (10 ml) was added and the mixture
was left overnight. The mixture was evaporated in vacuum, methanol was added (10 ml) and again
evaporated. Chromatography of the residue yielded following the compounds.
(20R)-5-Methyl-19-nor-5β-pregn-9-ene-3β,20-diyl diacetate (46, 143 mg, 6.7%), [α]D +44 (c 0.9).
IR spectrum: 1 734 (C=O); 1 653 (C=C); 1 243, 1 030 (C–O). For C25H38O4 (402.6) calculated:
74.59% C, 9.51% H; found: 74.29% C, 9.78% H;
(20R)-3β-Hydroxy-5-methyl-19-nor-5β-pregn-9-en-20-yl acetate (29, 821 mg, 43%) containing
15% of 36. Crystallization afforded pure compound 29, m.p. 139–140 °C (acetone–heptane), [α]D
+116 (c 1.1). IR spectrum: 3 615, 3 467 (O–H); 1 722 (C=O); 1 655 (C=C); 1 255, 1 044, 1 014
(C–O); 979 (C–OH). For C23H36O3 (360.5) calculated: 76.62% C, 10.06% H; found: 76.69% C,
10.39% H;
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Kasal, Polman, Budesinsky:
Diol 26, (799 mg, 47%) identical with starting material.
Hydrogenation of (20R)-5-Methyl-19-nor-5β-pregn-9-ene-3β,20-diol (26)
Diol 26 (4.0 g, 12.6 mmol) was hydrogenated as above, using platinum oxide (500 mg) in acetic acid
(55 ml). After 18 h stirring at 60 °C, the catalyst was filtered off and the filtrate evaporated. The
residue was dissolved in methanol (20 ml) and hydrolyzed by treatment with sodium methoxide in
methanol (0.87 M, 20 ml, 17.4 mmol) at 60 °C for 1 h. Chromatography on silica gel (500 g) in 2%
acetone in ligroin yielded the following fractions.
Fraction A: a mixture of isomers 27 and 28 (2.116 g, 53%). Crystallization from acetone–heptane
gave pure (20R)-5-methyl-19-nor-5β,9α,10β-pregnane-3β,20-diol (27, 910 mg, 23%), m.p. 174–175 °C,
[α]D +15 (c 0.9). IR spectrum: 3 615, 3 348, 3 359 (O–H); 1 018 (C–OH). For C21H36O2 (320.5)
calculated: 78.70% C, 11.32% H; found: 78.59% C, 11.28% H.
Fraction B: (20R)-5-Methyl-19-nor-5β,9β,10β-pregnane-3β,20-diol (17, 1.674 mg, 42%), m.p.
208–210 °C (acetone–heptane), [α]D +23 (c 1.0). IR spectrum: 3 609, 3 451 (O–H); 1 091 (C–OH).
For C21H36O2 (320.5) calculated: 78.70% C, 11.32% H; found: 78.65% C, 11.27% H.
Hydrogenation of (20R)-3β-Hydroxy-5-methyl-19-nor-5β-pregn-9-ene-20-yl Acetate (29)
Compound 29 (400 mg, 1.11 mmol) was hydrogenated as above, using platinum oxide (250 mg) in
acetic acid (20 ml) and ethanol (10 ml). After the usual workup, following fractions were obtained.
Fraction A: mixture of compounds 31 and 32 (167 mg, 42%). Crystallization from acetone–heptane
yielded (20R)-3β-hydroxy-5-methyl-19-nor-5β,9α,10β-pregnane-20-yl acetate (31, 97 mg, 24%), m.p.
159–160 °C, [α]D +41 (c 0.9). IR spectrum: 3 615 (O–H); 1 721 (C=O); 1 259, 1 026 (C–OH). For
C23H38O3 (362.6) calculated: 76.20% C, 10.56% H; found: 76.17% C, 10.59% H;
Fraction B: (20R)-3β-hydroxy-5-methyl-19-nor-5β,9β,10β-pregnane-20-yl acetate (30, 174 mg,
43%), identical with the sample prepared in another way.
Partial Acetylation of (20R)-5-Methyl-19-nor-5β,9β,10β-pregnane-3β,20-diol (17)
Diol 17 (560 mg, 1.75 mmol) was treated with acetic anhydride (3.3 ml, 34.9 mmol) in toluene (13
ml) and pyridine (5.5 ml) at ambient temperature. After 4 h, methanol (10 ml) was added and the
mixture was left overnight. The mixture was evaporated in vacuum, methanol was added (10 ml) and
again evaporated. Chromatography (40 g of silica gel, toluene–ethyl acetate, 10 : 1) of the residue
yielded following fractions.
Fraction A: (20R)-5-methyl-19-nor-5β,9β,10β-pregnane-3β,20-diyl diacetate (40, 148 mg, 21%),
m.p. 132–134 °C (methanol), [α]D +31 (c 1.0). IR spectrum: 1 722 (C=O); 1 378, 1 368 (CH3);
1 257, 1 025 (C–O). For C25H40O4 (404.6) calculated: 74.22% C, 9.97% H; found: 74.17% C, 9.92% H.
Fraction B: (20R)-20-hydroxy-5-methyl-19-nor-5β,9β,10β-pregnan-3β-yl acetate (39, 198 mg,
31%), [α]D +8 (c 1.0). IR spectrum: 3 623, 3 536 (O–H); 1 735 (C=O); 1 363 (CH3); 1 353, 1 249,
1 025 (C–O); 1 061 (C–OH). For C23H38O3 (362.6) calculated: 76.20% C, 10.56% H; found: 75.93% C,
10.72% H.
Fraction C: (20R)-3β-hydroxy-5-methyl-19-nor-5β,9β,10β-pregnan-20-yl acetate (30, 210 mg,
33%), [α]D +23 (c 1.0). IR spectrum: 3 620 (O–H); 1 730 (C=O); 1 377, 1 369 (CH3); 1 246, 1 067
(C–O); 1 021, 1 038 (C–OH). For C23H38O3 (362.6) calculated: 76.20% C, 10.56% H; found: 76.01% C,
10.49% H.
Fraction D: starting diol 26 (799 mg, 47%).
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

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1561
Partial Acetylation of (20R)-5-Methyl-19-nor-5β,9α,10β-pregnane-3β,20-diol (27)
Diol 27 (130 mg, 0.41 mmol) was treated with acetic anhydride (0.6 ml, 6.3 mmol) in toluene (2 ml)
and pyridine (0.9 ml) as above. Thin layer chromatography (4 PLC plates, benzene–ether, 3 : 1)
yielded following fractions.
Fraction A: (20R)-5-methyl-19-nor-5β,9α,10β-pregnane-3β,20-diyl diacetate (33, 17 mg, 10%),
[α]D +35 (c 1.0). IR spectrum: 1 722 (C=O); 1 368 (CH3); 1 266, 1 254, 1 027, 1 020 (C–O). For
C25H40O4 (404.6) calculated: 74.22% C, 9.97% H; found: 74.09% C, 9.94% H.
Fraction B: (20R)-3β-hydroxy-5-methyl-19-nor-5α,9α,10β-pregnan-20-yl acetate (31, 89 mg,
60%), m.p. 159–160 °C (acetone–heptane), [α]D +41 (c 1.3). IR spectrum: 3 615 (O–H); 1 721
(C=O); 1 363 (CH3); 1 259, 1 026 (C–OH). For C23H38O3 (362.6) calculated: 76.20% C, 10.56% H;
found:, 75.19% C, 10.58% H.
Fraction C: diol 27 (36 mg, 28%) identical with starting material.
Partial Oxidation of (20R)-5-Methyl-19-nor-5β,9α,10β-pregnane-3β,20-diol (27)
A solution of diol 27 (160 mg, 0.50 mmol) in acetone (50 ml) was cooled to –65 °C and the Jones
reagent (7 drops) was added under stirring. After 5 min, the temperature was allowed to rise to 20 °C.
An excess oxidant was decomposed by methanol (8 ml). After 20 min, the solution was filtered, con-
centrated in vacuum and mixed with a potassium hydrogen carbonate solution. The precipitate was
extracted with ether, washed with brine and dried over sodium sulfate. Thin layer chromatography (5 PLC
plates, benzene–ether, 1 : 1) yielded following fractions.
Fraction A: 5-methyl-19-nor-5β,9α,10β-pregnane-3,20-dione (2, 26 mg, 16%), identical with
compound prepared above.
Fraction B: 3β-hydroxy-5-methyl-19-nor-5β,9α,10β-pregnan-20-one (9, 3 mg, 2%), identical with
compound prepared in another way.
Fraction C: (20R)-20-hydroxy-5-methyl-19-nor-5β,9α,10β-pregnan-3-one (34, 93 mg, 58%), m.p.
146–147 °C (acetone–heptane), [α]D +22 (c 1.1). IR spectrum: 3 609, 3 475 (O–H); 1 704, 1 422
(CH2C=O); 1 085 (C–OH).
Fraction D: starting diol 27 (19 mg, 12%).
(20R)-5-Methyl-3-oxo-19-nor-5β,9α,10β-pregnan-20-yl Acetate (35)
Monoacetate 31 (72 mg, 0.20 mmol) was oxidized as above. The product was purified by chromato-
graphy (1 PLC plate, benzene–ether 4 : 1) and crystallized from acetone–heptane. M.p. 167–168 °C (63 mg,
88%), [α]D +58 (c 1.0). IR spectrum: 1 723, 1 260, 1 252, 1 236 (C–O, acetate); 1 711, 1 430, 1 422
(CH2C=O). For C23H36O3 (360.5) calculated: 76.62% C, 10.06% H; found: 76.51% C, 9.96% H.
(20R)-20-Hydroxy-5-methyl-19-nor-5β,9α,10β-pregnan-3-one (34)
A solution of sodium methoxide in methanol (0.87 M, 1 ml) was added to a solution of acetate 35 (93 mg,
0.26 mmol) in methanol (1 ml) and left aside under argon at ambient temperature. After 4 days,
acetic acid (0.7 ml) and ethyl acetate (5 ml) was added, the solution was concentrated to a half and
washed with brine and dried. The product was purified by PLC (2 plates, benzene–ether, 3 : 1). Elu-
tion of the major zone yielded compound 34 (74 mg, 90%) identical with the compound prepared by
partial oxidation of diol 27.
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Kasal, Polman, Budesinsky:
(20R)-20-Hydroxy-5-methyl-19-nor-5β,9β,10β-pregnan-3-one (45)
Analogously, acetate 42 (273 mg, 0.76 mmol) was hydrolyzed with sodium methoxide (0.87 M, 2 ml)
under argon. Preparative thin layer chromatography (5 plates, benzene–ether 3 : 1) yielded compound 45
(220 mg, 91%), [α]D –9 (c 1.2). IR spectrum: 3 611, 3 466 (O–H); 1 706, 1 419 (CH2C=O); 1 096
(C–OH). Mass spectrum, m/z (%): 318 (M+, 36), 300 (58), 285 (14), 271 (10), 242 (15), 231 (100),
217 (17), 213 (17). High resolution mass spectrum, m/z: for C21H34O2 calculated 318.255881, found:
318.256481.
Partial Hydrolysis of (20R)-5-Methyl-19-nor-5β,9β,10β-pregnane-3β,20-diyl Diacetate (40)
A solution of diacetate 40 (204 mg, 0.50 mmol) in methanol (4.5 ml) was treated with sodium meth-
oxide in methanol (0.87 M, 0.7 ml) at ambient temperature. After 20 h, the solution was acidified
with acetic acid (0.5 ml) and evaporated. The residue was separated by PLC (4 plates, benzene–ether,
1 : 1) into two fractions.
Fraction A: (20R)-3β-hydroxy-5-methyl-19-nor-5β,9β,10β-pregnan-20-yl acetate (30, 154 mg,
84%), identical by PLC and IR spectrum with the above sample.
Fraction B: (20R)-5-methyl-19-nor-5β,9β,10β-pregnane-3β,20-diol (17, 20 mg, 12%), identical
with the authentic sample.
5-Methyl-20-oxo-19-nor-5β,9β,10β-pregnan-3β-yl Acetate (43)
Compound 39 (110 mg, 0.30 mmol) was oxidized with the Jones reagent in acetone as above. Crude
product was purified by PLC (2 plates, benzene–ether, 4 : 1) to yield compound 39 (101 mg, 92%),
[α]D +64 (c 1.0). IR spectrum: 1 718, 1 728 shoulder, 1 700 (C=O); 1 259, 1 026 (C–O). For
C23H36O3 (360.5): calculated: 76.62% C, 10.06% H; found: 76.40% C, 10.16% H.
(20R)-5-Methyl-3-oxo-19-nor-5β,9β,10β-pregnan-20-yl Acetate (42)
Analogously, compound 30 (430 mg, 1.19 mmol) was converted to ketone 42 (398 mg, 93%). M.p.
147–148 °C (acetone–heptane), [α]D +31 (c 1.2). IR spectrum: 1 718 (C=O); 1 255, 1 043 (C–O).
For C23H36O3 (360.5) calculated: 76.62% C, 10.06% H; found: 76.59% C, 10.07% H.
3β-Hydroxy-5-methyl-19-nor-5β,9β,10β-pregnan-20-one (15)
A solution of acetate 43 (330 mg, 0.92 mmol) in methanol (8 ml) was treated with sodium methoxide
in methanol (0.87 M, 1.1 ml) under nitrogen atmosphere at ambient temperature. After 18 h, the sol-
ution was acidified with acetic acid (0.8 ml) and evaporated. The residue was partitioned between
ethyl acetate and brine, the organic layer was washed with water, dried over sodium sulfate and evaporated.
PLC (7 plates, benzene–ether 10 : 1) gave pure compound 15 (263 mg, 90%), [α]D +70 (c 1.0). Cir-
cular dichroism: ∆ε287 +2.91. IR spectrum: 3 607, 3 463 (O–H); 1 698 (C=O); 1 066, 1 020 (C–OH).
Mass spectrum, m/z (%): 318 (M+, 49), 303 (57), 300 (100), 285 (32), 233 (49), 215 (96). High resolu-
tion mass spectrum, m/z: for C21H34O2 calculated 318.255881, found 318.256481.
(20R)-20-Hydroxy-5-methyl-19-nor-5β-pregn-9-en-3-one (38)
a) Diol monoacetate 29 (112 mg, 0.31 mmol) was oxidized with the Jones reagent in acetone (2 ml)
as above. The crude product (37) was dissolved in methanol (3 ml) and treated with sodium methoxide
in methanol (0.87M, 1 ml) at room temperature in argon atmosphere. After 3 days, the mixture was
worked up and purified by PLC as in the preparation of compound 15. The major product was hy-
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

On Steroids
1563
droxy ketone 38 (26 mg, 26%) [α]D –3 (c 1.0). IR spectrum: 3 607 (O–H); 1 703, 1 416 (CH2–C=O);
1 085, 979 (C–OH). Mass spectrum, m/z (%): 316 (M+, 100), 301 (21), 298 (29), 283 (35), 271 (18),
257 (23), 243 (13), 231 (25), 213 (20). For C21H32O2 (316.5) calculated: 79.70% C, 10.19% H;
found: 79.57% C, 10.25% H.
b) Diol 26 (300 mg, 0.94 mmol) was dissolved in acetone (90 ml) and cooled to –60 °C. Jones
reagent14 (12 drops) was added under stirring, after 5 min the temperature was allowed to rise to
ambient temperature. After 45 min, methanol (10 ml) was added and the mixture was concentrated in
vacuum to a fifth of its volume. A potassium hydrogen carbonate solution (15 ml) was added and the
precipitate was extracted with chloroform, washed with water and dried over sodium sulfate. The
solution was evaporated and the residue purified by PLC (7 plates, benzene–ether 1 : 1). The major
product (38, 149 mg, 44%), identical with the above prepared sample, was obtained in addition to
diol 26 (65 mg, 22%) and dione 1 (39 mg, 13%).
Authors are indebted to Ms M. Sedlackova for skilled technical assistance, to Dr P. Fiedler for taking
and interpreting IR spectra, and to Dr S. Vasickova for measurements of CD. The project was supported
by the Grant Agency of the Academy of Sciences of the Czech Republic (grant No. A7045608) and the
Internal Grant Agency of the Ministry of Health of the Czech Republic (grant No. 51/1998).
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Collect. Czech. Chem. Commun. (Vol. 63) (1998)