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Biomimetic transformation of dehydrocurdione into curcumenol and isocurcumenol and their stereochemistries
Tetrahedron Letters,Vol.26,No.7,pp Printed in Great Britain
BIOMIMETIC AND
Yoshinori
TRANSFORMATION
ISOCURCUMENOL
Shiobara,
Faculty
Dehydrocurdione,
converted
to curcumenol,
tive manner
From
and their
the rhizome
sesquiterpenes
Bunri
cture
a sesquiterpene
absolute
730, Japan
isolated
from Curcuma
zedoaria,
or new spirolactones
zedoaria
were
we wish
.-a\
DehydrocurdioneL'
curcumenol
to report
since
we determined
sesquiterpenes,
(2) and isocurcumenol
treated
with
K2C03
lit.3)
+397")
vely.
On the other
(A), one of the compo-
cumenol amount
hand,
(2) ([aID +39.8', of 2. The optical
lly no racemization ated with
acids
of cyclization tive yield.
or alumina
stru-
of curcumenol 3, (2_) and
transformations
has been
assigned
of L
to these
of dehydrocurdione
I and highly
in benzene,
during
under
in 73% yield
of synthetic
(2) ([al,
argon
together
with
or A1C13,
respectiisocur-
a small
that essentia-
Interestingly,
L underwent
& was
+385',
afforded
2 and 2 revealed
the conversions.
BF3*Et20
When
selective.
curcumenol
in SO% and 87% yields,
of 1 at 230°C
+34.0°)
lit.4)
rotations
such as p-TsOH,
when
tre-
a different
type
raise
Extensive
functionalities,
simple
as the sole product pyrolysis
took place
giving
a germacrenedione
configurations
2
was obtained
related
(2) as shown below.
of $_ to 2 or 2 is quite in MeOH
biogenetically
the biomimetic
no stereochemistry
the absolute
!. Conversion
was
selec-
from the same plant.
Furthermore,
into 2 and 3.
in a highly
determined.
various
Roscoe,
7\
isolated."
In this communication
University,
Hiroshima
configurations
of Curcuma
isocurcumenol 4, (1) isolated
Asakawa,
University,
having of C. zedoaria, is a unique sesquiterpene and is considered to be the biogenetic precursor
nents
Q),
Tokushima
Hiroshima
isocurcumenol
have been
Yoshinori
Fukazawa#
770, Japan
of Chemistry,
Abstract:
Kodama,*
and Yoshimasa
Sciences,
Tokushima
INTO CURCUMENOL
STEREOCHEMISTRIES
Mitsuaki
Iwata,
Takemoto
of Pharmaceutical
#Department
OF DEHYDROCURDIONE
AND THEIR
Tomoko
Tsunematsu
0040-4039/85 $3.00 + .oo 81985 Pergamon Press Ltd.
913-916,1985
namely
to two spirolactones 5 and 2 (ca. 1:l) in quantitaspectral analysis 5) revealed that i and 2 have the same a set-Me,
a R,S-dimethyl-a,R-unsaturated-y-lactone
913
and
914
an isopropenyl
group.
of a quaternary rence
spectra
The Spiro
oxygen-bearing revealed
structures
carbon
the proximity
assigned
based
of i) the 14-Me group observed
on the presence
In the case of $ NOE diffeand H-6,
between
and ii) H-l
the 14-Me group and both and H-4. It is noteH-6 and H-l indicating that these compounds are epimeric at C-l. worthy that the same spirolactones were isolated from the crude drug zedoary, the dried rhizomes of C_. zedoaria, although they have not been detected in the In 2, however,
NOES were
were 5) by CMR.
fresh plants.
BrC6H4C021
P-
NaH
Figure
1
915
We now turned rationalization 2 was
first
our
attention
of the above
converted
X-ray
rated been
in Figure
penes
as well tally. 9)
Since
1.
rated
suggests
from the same conformation
nyl have
the same orientation.
at C-Y initiates
cyclic
double
bona
double
the reaction
proceeds
6_ was
Since,
transformed
stereochemistry
perspective
drawing
into
determined is illust-
the cyclization
bona
to give
determined
intermediate
regioselectively.
on pyrolysis
through
have been
unequivo-
that the cyclizations leading to 2 and 2 take (i.e. 5 10) ) in which the 15-Me and C -carbo5 In the case of base treatment, the anion gene-
is introduced
the exocyclic
generated
For this purpose,
99.5-101°C.
was unsuccessful,
of the spirolactones
The stereostructure place
conversions.
curcumenol (;) and isocurcumenol (3-jhave already 4) the absolute configurations of these sesquiter-
chemically, as those
of &, 2 and 2 and the
(6_), m.p.
and the absolute
The computer
analysis.
correlated
selective
analysis
234-236OC,
the epoxide6) (I), yjp. by X-ray
highly
to the e-bromobenzoate
the attempted
however,
to the stereostructures
The selective
can be rationalized
a six-membered
ring
8_ where
the endo-
formation
by assuming
transition
state
of
that
(e_b) and
that hydrogen is transferred intramolecularly as in the pyrolysis of preisoca11,121 In contrast, the spirolactones 4 and 5 should be formed
lamenediol.
independently conversion
from different
is observed
conformations
under
tion of the acid to the carbonyl zation novel
and concomitant
C-C bond
group
conditions.
of the enone
cleavage
resulting
no inter-
In this case, system
induces
coordina-
the cycli-
in the formation
of the
ring system.
We are indebted Tokyo,
to Prof.
for the measurement
T. Takahashi of high
References
1) H. Shibuya, H. Hikino,
C. Konno
cited
and Dr. T. ?Jurae, The University
resolution
mass
of
spectra.
and Notes
I. Miura
Y. Yamamoto,
(1982) and. references 2)
(i.e. 1," and l,d) because
the reaction
and I. Kitagawa,
Heterocycles,
$I, 215
therein.
and T. Takemoto,
Chem. ---
Pharm.
Bull.
(Tokyo),
and T. Takemoto,
Chem. ---
Pharm.
zp, 987
(1972). 3) H. Hikino, (Tokyo),
if&
4) H. Hikino, 959 5) 3:
39
Bull.
(1968).
K. Agatsuma
and T. Takemoto,
Chem. ---
Pharm.
Bull.
(Tokyo),
&z,
(1969). colrless
oil,
xmax 235 nm 1.18(1~,
s;
S. Numabe
Y. Sakurai,
m),
13-Me),
br.s;
H6),
1.65(1H,
(c=1.17, CHC13),
v 1738, m),
1.73(3H,
m),
2.82(1~,
ad, J=11.8,
(t), 42.8(d),
2:
6 13.1(q), 52.3(d), colorless
1666 cm-',
2.24(3H,
1.92(1H,
s; Hg), CMR;
169.9(s).
[a], -33.0°
(E 14000),
19.9(q), 89.6(s), oil,
br.s;
br.s;
m/z
234.1617
PMR; 6 0.87(3H, 15-Me),
12-Me),
1.8O(lH,
2.32(1H,
(C15H2202), d, J=6.8; m),
4.76(1H,
br.s;
23.3(t),
23.9(q),
24.3(s),
112.7(t),
Icrl, +24.2O
120.9(s),
1.84(3Hr
m; H4),
8.8; Hl),
Hg),
(c=1.44, CHC13),
m/z
br.
2.47(2H,
4.95(lH,
26.5(t),
143.8(s),
14-Me),
br.
27.6
149.1(s), 234.1612(C15
916
235 nm (E 14000), v 1740, 1644 cm-l, PMR; 6 0.97(3H, d, J=6.4; Xmax 1.48-1.64(2H, m), 1.67(3H, br.s; 15-Me), 1.84(3H, br.s; 13-Me),
H22D2)' 14-Me),
1.81-1.91(2H,
: H6),
m),
2.85(1H, 4.89(1H,
Hg),
5.68(1H,
data:
using
8) All computations Sakurai
J=16.6
H6),
4.76(1H,
br.s;
19.9(q),
22.0(q),
24.4(q),
27.4
91.6(s),
114.0(t),
120.8(s),
145.3
configuration
1588 cm-',
d, J=1.3),
d, J=8.7), prisms,
technique
i3,
d, J=6.3),
d, J=13.9),
7.94(2H,
2.14(1H,
d, J=8.7).
P212121,
a=12.222(4), b= Intensities with 20~55.0
2=4.
on a Syntex
radiation.
6 1.07(3H,
1.98(1H,
7.56(2H,
dispersion carried
P3 diffractometer
Of the 2686 independent The structure
of bromine out using
s.
was
has been
K. Harimaya,
T. Kawamata,
(Tokyo), 3,
3783
for MoKa
with
gra-
reflections
solved
by direct
and
Y. Iitaka
& Chem.
derivative
assigned
radiation.
the UNICSIII
Inst. Phys.
that 2 is a dehydro
of which
mechanics
1667,
by the block-diagonal least-squares method 8) of 8.64%. The absolute configuration was determined
were
showed
recently
and Y.-T.
program g.,
system
22, 69
of curcumol,
(1979).
the absolute
(S. Inayama,
Guo, Chem. ---
(T.
Pharm.
J.-F.
Gao,
Bull.
(1984). calculations
Discussions
formations.
56.0(d),
~Fo(>3a(lFol).
and K. Kobayashi,
10) Molecular
J=16.6;
br.d,
and refined
R-value
the anomalous
9) The result
br.d,
ii, V=2068.6(9)
MoKa
1583 had
atom methods
to the final
2.87(1H, 6 13.1(q),
orthorhombic
br.s),
by w-scan
phite-monochromated
heavy
2.49(1H,
s), 1.75(3H,
C22H2504Br,
collected
measured,
12-Me),
45.2(d),
c=13.389(4) _
12.641(3), were
br.s;
of z: v 1739,
s), 1.37(3H,
d, J=13.9),
Hl),
2.25(3H,
169.8(s).
properties
1.34(3H,
m),
Hg), CMR;
33.8(t),
(s), 148.9(s),
7) Crystal
t, J=7.8;
br.s;
(t), 30.8(t),
6) Spectral
2.02(1H,
showed
that
of the conformations
1. is one of the stable of 3;will
be reported
conelse-
where. 11) M. Niwa, 12) The
M. Iguchi
formation
bond
tends
bond
formation.
(Received
and S. Yamamura,
of 2 as a minor
to be directed
in Japan
Bull. Chem. Sot. Jpn., $2, 3148 (1976). ---product is explained by the fact that the C=G
towards
29 November
98-H when
1984)
Cl approaches
C5 during
the
BIOMIMETIC AND
Yoshinori
TRANSFORMATION
ISOCURCUMENOL
Shiobara,
Faculty
Dehydrocurdione,
converted
to curcumenol,
tive manner
From
and their
the rhizome
sesquiterpenes
Bunri
cture
a sesquiterpene
absolute
730, Japan
isolated
from Curcuma
zedoaria,
or new spirolactones
zedoaria
were
we wish
.-a\
DehydrocurdioneL'
curcumenol
to report
since
we determined
sesquiterpenes,
(2) and isocurcumenol
treated
with
K2C03
lit.3)
+397")
vely.
On the other
(A), one of the compo-
cumenol amount
hand,
(2) ([aID +39.8', of 2. The optical
lly no racemization ated with
acids
of cyclization tive yield.
or alumina
stru-
of curcumenol 3, (2_) and
transformations
has been
assigned
of L
to these
of dehydrocurdione
I and highly
in benzene,
during
under
in 73% yield
of synthetic
(2) ([al,
argon
together
with
or A1C13,
respectiisocur-
a small
that essentia-
Interestingly,
L underwent
& was
+385',
afforded
2 and 2 revealed
the conversions.
BF3*Et20
When
selective.
curcumenol
in SO% and 87% yields,
of 1 at 230°C
+34.0°)
lit.4)
rotations
such as p-TsOH,
when
tre-
a different
type
raise
Extensive
functionalities,
simple
as the sole product pyrolysis
took place
giving
a germacrenedione
configurations
2
was obtained
related
(2) as shown below.
of $_ to 2 or 2 is quite in MeOH
biogenetically
the biomimetic
no stereochemistry
the absolute
!. Conversion
was
selec-
from the same plant.
Furthermore,
into 2 and 3.
in a highly
determined.
various
Roscoe,
7\
isolated."
In this communication
University,
Hiroshima
configurations
of Curcuma
isocurcumenol 4, (1) isolated
Asakawa,
University,
having of C. zedoaria, is a unique sesquiterpene and is considered to be the biogenetic precursor
nents
Q),
Tokushima
Hiroshima
isocurcumenol
have been
Yoshinori
Fukazawa#
770, Japan
of Chemistry,
Abstract:
Kodama,*
and Yoshimasa
Sciences,
Tokushima
INTO CURCUMENOL
STEREOCHEMISTRIES
Mitsuaki
Iwata,
Takemoto
of Pharmaceutical
#Department
OF DEHYDROCURDIONE
AND THEIR
Tomoko
Tsunematsu
0040-4039/85 $3.00 + .oo 81985 Pergamon Press Ltd.
913-916,1985
namely
to two spirolactones 5 and 2 (ca. 1:l) in quantitaspectral analysis 5) revealed that i and 2 have the same a set-Me,
a R,S-dimethyl-a,R-unsaturated-y-lactone
913
and
914
an isopropenyl
group.
of a quaternary rence
spectra
The Spiro
oxygen-bearing revealed
structures
carbon
the proximity
assigned
based
of i) the 14-Me group observed
on the presence
In the case of $ NOE diffeand H-6,
between
and ii) H-l
the 14-Me group and both and H-4. It is noteH-6 and H-l indicating that these compounds are epimeric at C-l. worthy that the same spirolactones were isolated from the crude drug zedoary, the dried rhizomes of C_. zedoaria, although they have not been detected in the In 2, however,
NOES were
were 5) by CMR.
fresh plants.
BrC6H4C021
P-
NaH
Figure
1
915
We now turned rationalization 2 was
first
our
attention
of the above
converted
X-ray
rated been
in Figure
penes
as well tally. 9)
Since
1.
rated
suggests
from the same conformation
nyl have
the same orientation.
at C-Y initiates
cyclic
double
bona
double
the reaction
proceeds
6_ was
Since,
transformed
stereochemistry
perspective
drawing
into
determined is illust-
the cyclization
bona
to give
determined
intermediate
regioselectively.
on pyrolysis
through
have been
unequivo-
that the cyclizations leading to 2 and 2 take (i.e. 5 10) ) in which the 15-Me and C -carbo5 In the case of base treatment, the anion gene-
is introduced
the exocyclic
generated
For this purpose,
99.5-101°C.
was unsuccessful,
of the spirolactones
The stereostructure place
conversions.
curcumenol (;) and isocurcumenol (3-jhave already 4) the absolute configurations of these sesquiter-
chemically, as those
of &, 2 and 2 and the
(6_), m.p.
and the absolute
The computer
analysis.
correlated
selective
analysis
234-236OC,
the epoxide6) (I), yjp. by X-ray
highly
to the e-bromobenzoate
the attempted
however,
to the stereostructures
The selective
can be rationalized
a six-membered
ring
8_ where
the endo-
formation
by assuming
transition
state
of
that
(e_b) and
that hydrogen is transferred intramolecularly as in the pyrolysis of preisoca11,121 In contrast, the spirolactones 4 and 5 should be formed
lamenediol.
independently conversion
from different
is observed
conformations
under
tion of the acid to the carbonyl zation novel
and concomitant
C-C bond
group
conditions.
of the enone
cleavage
resulting
no inter-
In this case, system
induces
coordina-
the cycli-
in the formation
of the
ring system.
We are indebted Tokyo,
to Prof.
for the measurement
T. Takahashi of high
References
1) H. Shibuya, H. Hikino,
C. Konno
cited
and Dr. T. ?Jurae, The University
resolution
mass
of
spectra.
and Notes
I. Miura
Y. Yamamoto,
(1982) and. references 2)
(i.e. 1," and l,d) because
the reaction
and I. Kitagawa,
Heterocycles,
$I, 215
therein.
and T. Takemoto,
Chem. ---
Pharm.
Bull.
(Tokyo),
and T. Takemoto,
Chem. ---
Pharm.
zp, 987
(1972). 3) H. Hikino, (Tokyo),
if&
4) H. Hikino, 959 5) 3:
39
Bull.
(1968).
K. Agatsuma
and T. Takemoto,
Chem. ---
Pharm.
Bull.
(Tokyo),
&z,
(1969). colrless
oil,
xmax 235 nm 1.18(1~,
s;
S. Numabe
Y. Sakurai,
m),
13-Me),
br.s;
H6),
1.65(1H,
(c=1.17, CHC13),
v 1738, m),
1.73(3H,
m),
2.82(1~,
ad, J=11.8,
(t), 42.8(d),
2:
6 13.1(q), 52.3(d), colorless
1666 cm-',
2.24(3H,
1.92(1H,
s; Hg), CMR;
169.9(s).
[a], -33.0°
(E 14000),
19.9(q), 89.6(s), oil,
br.s;
br.s;
m/z
234.1617
PMR; 6 0.87(3H, 15-Me),
12-Me),
1.8O(lH,
2.32(1H,
(C15H2202), d, J=6.8; m),
4.76(1H,
br.s;
23.3(t),
23.9(q),
24.3(s),
112.7(t),
Icrl, +24.2O
120.9(s),
1.84(3Hr
m; H4),
8.8; Hl),
Hg),
(c=1.44, CHC13),
m/z
br.
2.47(2H,
4.95(lH,
26.5(t),
143.8(s),
14-Me),
br.
27.6
149.1(s), 234.1612(C15
916
235 nm (E 14000), v 1740, 1644 cm-l, PMR; 6 0.97(3H, d, J=6.4; Xmax 1.48-1.64(2H, m), 1.67(3H, br.s; 15-Me), 1.84(3H, br.s; 13-Me),
H22D2)' 14-Me),
1.81-1.91(2H,
: H6),
m),
2.85(1H, 4.89(1H,
Hg),
5.68(1H,
data:
using
8) All computations Sakurai
J=16.6
H6),
4.76(1H,
br.s;
19.9(q),
22.0(q),
24.4(q),
27.4
91.6(s),
114.0(t),
120.8(s),
145.3
configuration
1588 cm-',
d, J=1.3),
d, J=8.7), prisms,
technique
i3,
d, J=6.3),
d, J=13.9),
7.94(2H,
2.14(1H,
d, J=8.7).
P212121,
a=12.222(4), b= Intensities with 20~55.0
2=4.
on a Syntex
radiation.
6 1.07(3H,
1.98(1H,
7.56(2H,
dispersion carried
P3 diffractometer
Of the 2686 independent The structure
of bromine out using
s.
was
has been
K. Harimaya,
T. Kawamata,
(Tokyo), 3,
3783
for MoKa
with
gra-
reflections
solved
by direct
and
Y. Iitaka
& Chem.
derivative
assigned
radiation.
the UNICSIII
Inst. Phys.
that 2 is a dehydro
of which
mechanics
1667,
by the block-diagonal least-squares method 8) of 8.64%. The absolute configuration was determined
were
showed
recently
and Y.-T.
program g.,
system
22, 69
of curcumol,
(1979).
the absolute
(S. Inayama,
Guo, Chem. ---
(T.
Pharm.
J.-F.
Gao,
Bull.
(1984). calculations
Discussions
formations.
56.0(d),
~Fo(>3a(lFol).
and K. Kobayashi,
10) Molecular
J=16.6;
br.d,
and refined
R-value
the anomalous
9) The result
br.d,
ii, V=2068.6(9)
MoKa
1583 had
atom methods
to the final
2.87(1H, 6 13.1(q),
orthorhombic
br.s),
by w-scan
phite-monochromated
heavy
2.49(1H,
s), 1.75(3H,
C22H2504Br,
collected
measured,
12-Me),
45.2(d),
c=13.389(4) _
12.641(3), were
br.s;
of z: v 1739,
s), 1.37(3H,
d, J=13.9),
Hl),
2.25(3H,
169.8(s).
properties
1.34(3H,
m),
Hg), CMR;
33.8(t),
(s), 148.9(s),
7) Crystal
t, J=7.8;
br.s;
(t), 30.8(t),
6) Spectral
2.02(1H,
showed
that
of the conformations
1. is one of the stable of 3;will
be reported
conelse-
where. 11) M. Niwa, 12) The
M. Iguchi
formation
bond
tends
bond
formation.
(Received
and S. Yamamura,
of 2 as a minor
to be directed
in Japan
Bull. Chem. Sot. Jpn., $2, 3148 (1976). ---product is explained by the fact that the C=G
towards
29 November
98-H when
1984)
Cl approaches
C5 during
the