Steroidal ketones from the sponge geodia cydonium


Migliuolo, A.; Piccialli, V.; Sica, D.

Lloydia 53(5): 1262-1266

1990


Four 4-ene-3,6-diketosteroids 1-4 have been isolated from the sponge Geodia cydonium along with 4-ene-3-ketosteroids 5-8. The structure of these compounds was deduced by analysis of spectral data. Partial synthesis of compound 1 confirmed the structure assignment of 4-ene-3,6-diketones.

1262
Journal
of
Natural
Products
Vol.
53,
No.
5,
pp.
1262-1266,
Sep-Oct
1990
STEROIDAL
KETONES
FROM
THE
SPONGE
GEODIA
CYDONIUM
ANNA
MIGLIUOLO,
VINCENZO
PICCIALLI,
and
DONATO
SICA*
Dipartimento
di
Chimica
Organica
e
Biologica,
University
di
Napoli,
via
Mezzocannone
16,
80134
Napoli,
Italy
ABSTRACT.—Four
4-ene-3,6-diketosteroids
1-4
have
been
isolated
from
the
sponge
Geo-
dia
cydonium
along
with
4-ene-3-ketosteroids
5-8.
The
structure
of
these
compounds
was
de-
duced
by
analysis
of
spectral
data.
Partial
synthesis
of
compound
1
confirmed
the
structure
as-
signment
of
4-ene-3,6-diketones.
As
part
of
our
continuing
research
on
polyoxygenated
steroids
from
sponges
(1-6)
we
now
report
the
isolation
and
the
characterization
of
steroidal
4-ene-3,6-diketones
1-4
obtained
from
the
marine
sponge
Geodia
cydonium
(
Jameson)
(order
Choristida,
rather
common
metabolites
of
biological
importance
in
marine
organisms
(7-13).
RESULTS
AND
DISCUSSION
The
Et
2
O-soluble
material
from
the
Me
2
CO
and
CHC1
3
-MeOH
(1:1)
extracts
of
the
sponge
was
chromatographed
on
a
Si
gel
column.
The
fractions
eluted
with
CHC1
3
slightly
before
sterols
were
further
separated
by
normal
phase
hplc
on
Si
gel
into
the
4-
ene-3,6-diketo-
and
4-ene-3-keto-steroid
fractions.
Final
separation
of
the
above
frac-
4-ENE-
3
,
6-DIKETOSTEROIDS.
—Steroid
1
had
the
molecular
formula
C
27
H
42
0
2
deduced
by
hrms.
The
mass
spectrum
contained
the
molecular
ion
at
m/z
398
with
sig-
nificant
fragment
ions
at
m/z
285
[M
C
8
H
17
]
+
and
243
[M
42
C
8
H
17
)
+
indicat-
ing
the
presence
of
a
C
8
H
17
saturated
side
chain.
The
'Fl-nmr
spectrum
contained
a
sig-
nal
at
8
6.17
for
a
trisubstituted
double
bond
(bs,
H-4)
and
five
methyl
resonances
of
a
cholestane
structure:
singlets
at
8
0.72
and
1.17
(H
3
-18
and
H
3
-19,
respectively)
and
doublets
at
8
0.93
(H
3
-21)
and
0.87
(H
3
-26
and
H
3
-27).
The
"C-nmr
spectrum
con-
firmed
the
presence
of
a
carbon-carbon
double
bond
(8
160.8,
125.2)
and
indicated
the
presence
of
two
conjugated
carbonyl
functions
(8
199.1,
201.9).
In
the
it
spectrum
1
R=
2
R=
3
R=
4
R=
5
R=
6
R=
7
R=
8
R=
Sep-Oct
1990)
Migliuolo
et
al.:
Steroidal
Ketones
1263
only
one
band
at
1686
cm
-1
was
present
for
the
carbonyl
groups.
Strong
peaks
at
mlz
136,
137
(fission
of
bonds
6-7
and
9-10)
and
259
(fission
of
bonds
7-8
and
9-10)
in
the
mass
spectrum
of
1
suggested
that
it
was
a
4-ene-3,6-diketone
(14,15).
This
was
sup-
ported
by
the
uv
spectrum,
which
showed
absorption
at
A
max
250
nm
(16),
and
by
1
H-
nmr
experiments,
which
facilitated
the
identification
of
the
structural
fragment
(from
C-1
to
C-7)
containing
the
enedione
moiety.
Two
deshielded
resonances
at
8
2.54
(ddd)
and
2.45
(bddd)
were
assigned
to
protons
attached
to
a
methylene
carbon
(C-2)
a
to
the
unsaturated
carbonyl-containing
function.
Support
for
this
connectivity
came
from
the
observation
of
a
long
range
coupling
between
the
proton
at
8
2.45
and
the
olefinic
pro-
ton
at
8
6.17.
The
multiplicities
of
the
resonances
at
8
2.54
and
2.45
required
that
these
protons
have
two
vicinal
neighbors
(H
2
-1).
Indeed
double
resonance
experiments
demonstrated
that
they
each
were
coupled
with
two
protons
resonating
at
8
2.15
and
1.91,
which
showed
to
be
coupled
with
each
other
and
with
no
other
protons.
Reso-
nances
at
8
2.68
and
2.04
(both
double
doublets)
were
assigned
to
the
protons
of
a
methylene
group
(CH
2
-7)
attached
to
the
other
side
of
the
enedione
portion.
The
mul-
tiplicities
of
these
signals
required
that
they
have
only
one
vicinal
neighbor
(H-8).
The
13
C-nmr
spectrum
of
1
showed
that
the
side
chain
of
this
steroid
was
of
the
cholestane
type (17).
All
the
above
observations
were
consistent
with
the
cholest-4-ene-3,6-dione
structure
1
for
this
compound.
Compound
1
has
not
been
found
as
a
naturally
occurring
steroid
but
has
been
previ-
ously
synthesized
(18).
An
authentic
specimen
prepared
from
cholesterol
according
to
a
procedure
described
in
the
literature
(18)
was
identical
in
all
respects
with
the
naturally
occurring
steroid
1.
The
presence
of
the
m/z
285
(loss
of
the
side
chain),
243
[M
-
42
-
side
chain1
+
,
136,
and
137
peaks
in
the
mass
spectra
of
all
four
enediones
1-4
indicated
that
they
possessed
a
common
4-ene-3,6-dione
structure
in
their
steroidal
skeleton
and
differed
only
in
the
side
chain.
This
was
confirmed
by
their
1
1-1-nmr
spectra
that
showed
identi-
cal
chemical
shift
values
for
the
H
2
-2,
H-4,
H2-7,
H
3
-18,
and
H
3
-19
resonances.
Steroid
2
had
the
molecular
formula
C
28
H4
2
0
2
deduced
by
hrms.
The
ions
at
miz
285
[M
-
C
9
H
17
3
+
and
243
[M
-
42
-
C
9
H
17
)
+
established
the
presence
of
a
C
9
H
17
monounsaturated
side
chain.
The
1
H-nmr
spectrum
displayed
methyl
doublets
at
8
1.03
and
1.02
(H
3
-26
and
H
3
-27)
and
0.97
(H
3
-21)
and
two
broad
singlets
for
a
terminal
methylene
group
at
8
4.72
and
4.66
(H
2
-28)
also
evident
in
the
13
C-nmr
spec-
trum
(8
106.1
and
156.6),
suggesting
that
this
sterol
was
the
previously
described
24-
methylenecholest-4-ene-3,
6-dione
(19).
Compound
3
had
the
molecular
formula
C
28
H4
2
0
2
(from
hrms).
Ions
at
miz
285
[M
-
C
9
H
17
1
+
and
243
[M
-
42
-
C
9
H
17
J
+
indicated
for
the
new
compound
a
side
chain
having
one
degree
of
unsaturation
and
a
C
9
H
17
composition.
The
1
H-nmr
chemi-
cal
shifts
for
the
side
chain
protons
of
this
ketosteroid
are
consistent
with
those
of
an
au-
thentic
sample
of
brassicasterol.
Evidence
supporting
the
above
observation
was
ob-
tained
from
spin
decoupling
experiments.
Irradiation
of
the
allylic
proton
at
8
2.01
(m,
H-20)
collapsed
the
double
doublet
at
8
5.13
(H-22)
to
a
doublet
(J
=
15.4
Hz)
and
the
H
3
-21
methyl
doublet
at
8
1.029
to
a
singlet.
The
H-22
proton
at
8
5.13
was
also
coupled
to
the
olefinic
double
doublet
at
8
5.20
(H-23).
Irradiation
of
the
allylic
proton
at
8
1.45
(H-25)
collapsed
the
two
methyl
doublets
centered
at
8
0.83
and
0.81
(H
3
-26
and
H
3
-27)
to
singlets,
showing
the
presence
of
one
isopropyl
group.
These
data,
in
conjunction
with
the
presence
of
a
further
methyl
resonance
at
8
0.91
(H
3
-28),
estab-
lished
a
(22E,24R)-24-methylcholesta-4,22-diene-3,6-dione
structure
3
for
this
steroid.
The
configuration
of
the
A
22
double
bond
was
established
to
be
E
on
the
basis
of
the
value
(15.4
Hz)
of
the
H-22-H-23
coupling
constant.
Compound
4
had
molecular
formula
C
2
8H4
2
0
2
.
The
close
similarity
of
the
mass
1264
Journal
of
Natural
Products
[Vol.
53,
No.
5
and
1
14-nmr
spectra
of
compounds
4
and
3
suggested
that
the
two
steroids
must
be
C-
24
epimers.
The
H
3
-21
doublet
in
the
1
H-nmr
spectrum
of
4
was
shifted
upfield
(8
1.019)
(20)
when
compared
to
the
corresponding
H
3
-21
signal
(8
1.029)
for
the
steroid
3;
hence
4
must
be
formulated
as
(22E,24S)-24-methylcholesta-4,22-diene-3,6-
dione.
4-ENE-3-KETOSTEROIDS.—The
mass
spectra
of
steroids
5-8
exhibited
intense
peaks
at
m/z
229
[M
42
side
chair
e
and
124
(fission
of
the
6-7
and
9-10
allylic
bonds)
characteristic
of
0
4
-3-ketosteroids
(15,21).
The
presence
of
m/z
271
[M
side
chain)
+
and
229
[M
42
side
chain)
+
peaks
in
the
mass
spectra
of all
four
steroids
indicated
that
they
possessed
identical
nuclei,
with
the
structural
difference
between
these
compounds
being
confined
to
the
nature
of
the
side
chains.
This
was
confirmed
by
their
1
H-nmr
spectra
that
showed
identical
chemical
shift
values
for
the
H-4,
H
3
-18,
and
H
3
-19
protons.
Steroids
5
and
6
were
shown
to
be
identical
with
the
earlier
reported
4-ene-3-keto-
steroids
(9).
Steroids
7
and
8
could
not
be
separated
by
reversed-phase
hplc.
They
each
had
the
molecular
formula
C
29
H
48
0
and
a
C
10
H
21
-saturated
side
chain.
Their
1
H-nmr
spec-
trum
was
composed
of
signals
from
the
two
epimers
at
C-24.
The
side
chain
methyl
sig-
nals
for
both
isomers
were
assigned
by
comparison
with
those
of
authentic
samples
of
sitosterol
and
clionasterol.
Mixtures
of
C-24
epimeric
24-ethylcholest-4-en-3-ones
have
previously
been
iso-
lated
from
marine
organisms
(11).
Compound
6
is
the
major
component
of
the
4-ene-3-ketosteroid
mixture.
From
a
biosynthetic
point
of
view
it
seems
probable
that
4-ene-3,6-diketosteroids
1-4
could
derive
from
the
corresponding
4-ene-3-ketosteroids
which,
in
turn,
are
likely
biogenetically
related
to
the
A
5
-3P-monohydroxysterols
present
in
the
sponge
(22).
EXPERIMENTAL
GENERAL
EXPERIMENTAL
PROCEDURES.—'H-
and
'
3
C-nmr
spectra
were
recorded
on
a
WM-400
spectrometer
in
CDC1
3
solutions.
1
11
chemical
shifts
were
refereenced
to
the
residual
CHC1
3
signal
(7.26
ppm).
13
C
chemical
shifts
were
referenced
to
CDC1
3
(77.0
ppm).
Low
resolution
mass
spectra
were
deter-
mined
at
70
eV
with
an
AEI
MS
30
mass
spectrometer.
High
resoluton
mass
spectra
were
recorded
on
a
Kratos
MS
50
spectrometer.
Ft-ir
spectra
were
obtained
with
a
Perkin-Elmer
1760-X
FT-ir.
Uv
spectra
were
recorded
using
a
Perkin-Elmer
Model
550S
spectrophotometer
and
MeOH
solvent.
Hplc
was
carried
out
on
a
Varian
2510
pump
and
a
Waters
Associates
R403
differential
refractometer.
Melting
points
were
determined
on
a
Kofler
apparatus
and
are
uncorrected.
EXTRACTION
AND
ISOLATION.—The
sponge
G.
cydonium,
identified
by
Dr.
G.
Corriero,
Univer-
sity
of
Genova,
was
collected
by
hand
at
depths
of
10
to
15
m
near
Bacoli
in
the
Bay
of
Naples
in
September
1989.
A
voucher
specimen
is
on
file
at
our
laboratories.
The
freshly
collected
sponge
(202
g
dry
wt
after
ex-
traction)
was
extracted
one
time
with
Me
2
CO
and
two
times
with
CHC1
3
-MeOH
(1:1).
Removal
of
the
sol-
vents
under
reduced
pressure
left
an
aqueous
suspension
which
was
extracted
with
Et
2
O.
Evaporation
of
the
Et
2
O
layer
afforded
2.04
g
of
crude
extract
which
was
fractionated
on
an
open
Si
gel
column
(200
g,
3
cm
diameter)
using
CHC1
3
as
eluent;
100-ml
fractions
were
collected.
Fractions
9-11
(one
spot
on
tic),
eluted
slightly
before
monohydroxylated
sterols,
contained
4-en-3-one
and
4-ene-3,6-dione
steroids
that
were
separated
by
normal
phase
hplc
on
a
Si
gel
column
(Hibar
LiChrosorb
Si-60,
250
X
4
mm)
using
hexane-
EtOAc
(9:1)
as
the
mobile
phase.
The
more
polar
fraction
obtained
from
this
separation,
containing
4-ene-
3,6-dione
steroids
(4.5
mg),
was
fractionated
by
reversed-phase
hplc
on
a
Hibar
Superspher
RP-18
(250
X
4
mm)
column
eluted
with
MeCN
to
give
pure
1(2.2
mg),
2
(1.0
mg),
3
(0.4
mg),
and
4
(0.7
mg).
The
fraction
containing
4-en-3-one
steroids
(7
mg)
was
subjected
to
reversed-phase
hplc
on
the
above
col-
umn
using
MeOH
as
eluent
to
give
steroids
5
(2.0
mg),
6
(3.5
mg),
and
7
and
8
(together
1.0
mg),
which
were
identified
from
their
1
1-1-nmr
and
mass
spectral
data.
SPECTRAL
DATA.—Cholest-4-ene-3,6-dione
[11.—Mp
123-125
°
(MeOH)
[lit.
(18)
124-125
°
];
it
(CHC1
3
)
v
max
1686
cm
-1
;
uv
X
max
(MeOH)
250
nm
(E
=
12300);
'II
nmr
(CDC1
3
,
400
MHz)
8
6.17
Sep-Oct
1990)
Migliuolo
et
al.:
Steroidal
Ketones
1265
(1H,
bs,
4-H),
2.68
(1H,
dd,
J=
14.6
and
3.7
Hz,
Ha-7),
2.54
(1H,
ddd,
J=
17.5,
17.5
and
5.1
Hz,
Ha-2),
2.45
(1H,
bddd,
J
=
17.5,
5.1,
and
3.2
Hz,
Hb-2),
2.15
(1H,
m,
partially
overlapped
to
other
signals,
Ha-1),
2.04
(1H,
dd,
J=
14.6
and
13.0
Hz,
Hb-7),
1.91(m,
overlapped
to
other
signals,
Hb-1),
1.17
(3H,
s,
H
3
-19),
0.93
(3H,
d,
J=
6.6
Hz,
H
3
-21),
0.87
(6H,
d,
J=
6.7
Hz,
H
3
-26
and
H
3
-27),
0.72
(3H,
s,
H
3
-18);
I3
C
nmr
(CDC1
3
,
100.1
MHz)
8
35.5
(C-1),
33.8
(C-2),
199.1(C-3
or
C-6),
125.2
(C-4),
160.8
(C-5),
201.9
(C-6
or
C-3),
46.6
(C-7),
34.0
(C-8),
50.8
(C-9),
39.0
(C-10),
20.7
(C-11),
39.3
(C-12),
42.3
(C-13),
55.8
(C-14),
23.6
(C-15
or
C-23),
27.8
(C-16),
56.4
(C-17),
11.7
(C-18),
17.3
(C-19),
35.3
(C-20),
18.5
(C-21),
35.9
(C-22),
23.8
(C-23
or
C-15),
39.6
(C-24),
27.8
(C-25),
22.4
(C-
26
or
C-27),
22.7
(C-27
or
C-26)
[carbon
multiplicities
were
determined
through
DEPT
experiments;
nu-
clear
carbon
assignments
were
facilitated
using
cholest-4-en-3-one
(17)
as
a
model
compound);
lreims
m/z
(rel.
int.)
[M1
+
398
(25),
[M
-
Me)
+
383
(9),
(NI-
CH
2
C0)
+
356
(9),
[M
-
side
chain}
*
285
(16),
[M
-
side
chain
-
281
*
257
(12),
[rings
C
and
D,
and
side
chain]
.*
247
(21),
[M
-
42
-
side
chain)
+
243
(42),
(C
8
1-1
9
0
2
)
*
137
(100),
[C
8
H
8
0
2
1
+
136
(55);
hreims
m/z
398.3170
(C
27
H
42
0
2
requires
398.3185).
24-Methylenecholest-4-ene-3,6-dione
(2).—Mp
130-132
°
(MeOH);
it
v
max
1686
cm
-I
;
uv
X
max
(MeOH)
250
nm
(e
=
12300);
1
14
nmr
(CDC1
3
,
400
MHz)
8
6.17
(1H,
bs,
H-4),
4.72
(1H,
bs,
Ha-28),
4.66
(1H,
bs,
Hb-28),
2.68
(1H,
dd,
J=
14.6
and
3.7
Hz,
Ha-7),
2.54
(1H,
ddd,
J=
17.7,
17.7,
and
5.1
Hz,
Ha-2),
2.45
(1H,
bddd,
J
=
17.7,
5.1,
and
3.2
Hz,
Hb-2),
2.23
(1H,
septet,
J=
6.7
Hz,
H-25),
2.15
(1H,
m,
partially
overlapped
to
other
signals,
Ha-1),
2.04
(1H,
dd,
J=
14.5
and
12.8
Hz,
Hb-7),
1.91
(m,
overlapped
to
other
signals,
Hb-1),
1.16
(3H,
s,
H
3
-19),
1.03
and
1.02
(3H
each,
d's,
both
J=
6.7
Hz,
H
3
-26
and
H
3
-27),
0.97
(3H,
d,
J
=
6.7
Hz,
H
3
-21),
0.72
(3H,
s,
H
3
-18);
13
C
nmr
(CDC1
3
,
100.1
MHz)
8
35.5
(C-1),
33.8
(C-2),
199.5
(C-3
or
C-6),
125.5
(C-4),
161.0
(C-5),
202.4
(C-6
or
C-3),
46.8
(C-7),
34.0
(C-8),
50.9
(C-9),
39.1
(C-10),
20.8
(C-11),
39.8
(C-12),
42.5
(C-13),
55.8
(C-14),
23.9
(C-15),
28.0
(C-16),
56.5
(C-17),
11.9
(C-18),
17.5
(C-19),
35.6
(C-20),
18.6
(C-21),
34.5
(C-22),
30.9
(C-23),
156.6
(C-24),
34.2
(C-25),
21.8
(C-26
or
C-27),
22.0
(C-27
or
C-26),
106.1
(C-28);
Ireims
m/z
(rel.
int.)
[Mr
*
410
(6),
[M
-
MO
+
395
(6),
[M
-
CH
2
C01
*
368
(3),
[M
-
C
6
H
12
)
*
326
(48),
[M
-
C
6
I-1
12
-
CH
3
]
*
311
(36),
285
(9),
[M
-
side
chain
-
2H)
+
283
(31),
[rings
C
and
D,
and
side
chain)
*
259
(31),
257
(62),
243
(31),
137
(100),
136
(22);
hreims
m/z
410.3170
(C
28
H
42
0
2
requires
410.3185).
(22E,24R)-24-Methylcholesta-4,22-diene-3,6-dione
[3).—Ir
(CHC1
3
)
v
max
1686
cm
-1
;
uv
X
max
250
nm
(E
=
12300);
1
1-1
nmr
(CDC1
3
,
400
MHz)
8
6.17
(1H,
bs,
H-4),
5.20
(1H,
dd,
J
=
15.4
and
6.8
Hz,
H-23),
5.13
(1H,
dd,
J=
15.4
and
7.5
Hz,
H-22),
2.67
(1H,
dd,
J=
14.5
and
3.6
Hz,
Ha-7),
2.54
(1H,
ddd,
J
=
17.5,
17.5,
and
5.1
Hz,
Ha-2),
2.45
(1H,
bddd,
J=
17.5,
5.1,
and
3.2
Hz,
Hb-2),
2.15
(1H,
m,
overlapped
to
other
signals,
Ha-1),
2.04
(1H,
dd,
J=
14.5
and
12.8
Hz,
Hb-7),
1.91
(m,
over-
lapped
to
other
signals,
Hb-1),
1.17
(3H,
s,
H
3
-19),
1.029
(3H,
d,
J=
6.7
Hz,
H
3
-21),
0.91
(3H,
d,
J=
6.7
Hz,
H
3
-28),
0.83
and
0.81(3H
each,
d's,
both
J
=
6.7
Hz,
H-26
and
H
3
-27),
0.72
(3H,
s,
H
3
-
18);
lreims
m/z
(rel.
int.)
[M1
+
410
(20),
395
(4),
368
(6),
[M
-
C
3
H
7
)
367
(16),
285
(75),
283
(40),
259
(15),
257
(31),
243
(32),
137
(100),
136
(20);
hreims
m/z
410.3199
(C
28
H
42
0
2
requires
410.3185).
(22E,24S)-24-Methylchole.sta-4,22-diene-3,6-dione[4).—Ir
(CHC1
3
)
v
max
1686
cm
-1
;
uv
X
max
250
nm
(E
=
12300);
1
1-I
nmr
(CDC1
3
,
400
MHz)
8
6.17
(1H,
bs,
H-4),
5.20
(1H,
dd,
J=
15.4
and
6.8
Hz,
H-23),
5.13
(1H,
dd,
J=
15.4
and
7.5
Hz,
H-22),
2.67
(1H,
dd,
J=
14.5
and
3.6
Hz,
Ha-7),
2.54
(1H,
ddd,J=
17.5,
17.5,
and
5.1
Hz,
Ha-2),
2.45
(1H,
bddd,
J=
17.5,
5.1,
and
3.2
Hz,
Hb-2),
2.15
(1H,
m,
overlapped
to
other
signals,
Ha-1),
2.04
(1H,
dd,
J=
14.5
and
12.8
Hz,
Hb-7),
1.91
(m,
overlapped
to
other
signals,
Hb-1),
1.17
(3H,
s,
H
3
-19),
1.019
(3H,
d,
J=
6.7
Hz,
H
3
-21),
0.91
(3H,
d,
J=
6.7
Hz,
H
3
-28),
0.83
and
0.81
(3H
each,
d's,
both
J=
6.7
Hz,
H
3
-26
and
H
3
-27),
0.72
(3H,
s,
H
3
-18);
lreims
m/z
[M1
+
410
(11),
395
(2),
368
(10),
367
(10),
285
(25),
283
(21),
259
(7),
257
(16),
243
(15),
137
(100),
136
(22);
hreims
m/z
410.3176
(C
28
H
42
0
2
requires
410.3185).
ACKNOWLEDGMENTS
This
research
was
supported
by
Ministero
della
Pubblica
Istruzione.
We
thank
the
Stazione
Zoologica
di
Napoli
for
supplying
the
sponge.
Mass
spectral
data
were
provided
by
the
Servizio
di
Spettrometria
di
Massa
del
CNR
e
dell'Universita
di
Napoli.
The
assistance
of
the
staff
is
gratefully
acknowledged.
Thanks
are
also
due
to
Dr.
G.
Corriero,
University
of
Genova,
for
taxonomic
identification
of
the
sponge.
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and
D.
Sica,
J.
Nat.
Prod.,
50,
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A.
Madaio,
V.
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D.
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53,
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G.
Notaro,
V.
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and
D.
Sica,
J.
Nat.
Prod.,
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press.
7.
L.G.
Goad,
in:
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Natural
Products:
Chemical
and
Biological
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Ed.
by
P.
Scheuer,
Academic
Press,
New
York,
1978,
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II,
p.
75.
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F.J.
Schimtz,
in:
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Natural
Products:
Chemical
and
Biological
Perspectives."
Ed.
by
P.
Scheuer,
Academic
Press,
New
York,
1978,
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p.
241.
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Y.M.
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525
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T.B.
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C.
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W.C.M.C.
Kokke,
W.
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C.
Djerassi,
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40,
307
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S.
Popov,
R.M.K.
Carlson,
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C.
Djerassi,
Steroids,
41,
537
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C.
Djerassi,
J.
Karliner,
and
R.
Aplin,
Steroids,
6,
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Z.V.
Zaretskii,
"Mass
Spectrometery
of
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Israel
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Press,
Jerusalem,
1976.
16.
L.F.
Fieser
and
M.
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"Steroids,"
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New
York,
1959,
p.
21.
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J.W.
Blunt
and
J.B.
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L.F.
Fieser,
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35,
36
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M.
Tischler,
S.W.
Ayer,
R.J.
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J.F.
Mitchell,
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J.
Clardy,
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J.
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1173
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Y.
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C.
Djerassi,
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2420
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Received
19
February
1990