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Yamataimine, a new pyrrolizidine alkaloid from Cacalia yatabei
Tetrahedron
Letters
NO. 8, PP 767 - 770,
1978.
Pargamon
Press.
YAMATAIMINE,A NEW PYRROLIZIDINE FROM CACALIA
School of Pharmaceutical
Sciences,
Kitasato Yoichi
Faculty
of Pharmaceutical
Sciences,
(Received in Japan 5 December 1977;
a new pyrrolizidine
Cacalia yatabei
Maxim.
name
the results of chemical The crude alkaloid
activity
ClBH2705N(M+
are showing
tained by IR spectral responsible spectrum
for two olefinic
of l_shows
protons
geminal methylene
determination
1 is classified rv are at 0.82ppm
(3H, t, J=7.5Hz)
protons
cyclic
337.189),
pyrrolizidine
from the roots of
by discussing
was chromatographed
system to yield
1, colorless
signals of carbons2, carbons,
The signals
of which
(H=l.22ppm)
for Ct13-CH2-C-15, 0.98ppm
macrocyclic
of retronecine4.
767
signals
at
resonance(PMR)
pyrrolizidine
the olefinic
alkaloid.3
proton()C=Ci-)
at C-2,
The signals of the
at 65.52 and 4.30(J=l1.5Hz).
and the coupling alkaloid.
constant
(J=ll.5Hz),
Other assignable
(3H, d, J=8.0Hz)
signals
for Cti3-CH- and 1.18ppm
peaks at 1.25 to 3.50ppm
protons
studies
needles,
at 135.7 and 131.4 are
The proton magnetic
pyrrolizidine
The complicated
on
which are also ascer-
) at C-7 and C-8, respectively.
macrocyclic
mass spectrometric
derivatives
in Compo-
[ol]b8+63.6'(EtOH).
of twelve membered
at C-3, C-5 and C-6 and methine
The high resolution
solvent
in the necine moiety.
of the shift
respectively.
1978)
analysis.
at C-9 appear as a pair of doublet
differences
was isolated
of two ester carbonyl
and >Cl-N<
as a twelve membered
(3H, s) for Ci3-C-12, methylene
(>Cy-OCO-
113 Japan
alkaloids
of yamataimine
at 66.10, 4.98 and 3.85ppm correspond
protons
From the appreciable
pattern
Tokyo,
of pyrrolizidine
-1 KBr at vmax 1720 and 1735cm .
carbons
a typical
The three broad singlets and two methine
the presence
absorption
108 Japan
: yama-taimingasa)
of 1 shows 18 detectable N
spectrum
Bunkyo-ku,
from MeOH ext. of the roots(2.2kg)
m.p. 181-182"(petroleum-acetone),
174.4 and 173.9ppm
of Tokyo,
study and X-ray crystallographic extracted
Tokyo,
Iitaka
silica gel column and eluted with CHCl3-MeOH-NH40H
The I3 C-NMR(CMR)
Minato-ku,
named yamataimine(1)
paper deals with the structural
The present
Furuya*
received in UK for publication 6 Jaa~a~
alkaloid,
(Japanese
Britain.
ALKALOID
University,
University
In the course of the studies on carcinogenic sitae plants,
in Great
YATABEI'
and Tsutomu
Manabu Hikichi
Frinted
are due to the
at C-13 and C-15.
on this alkaloid The fragment
show also a typical macro-
ions at m/e 138(C8H120N),
768
121(C8H,,N)
No. 8
The significant
and 95 (C6HgN 100%) arose from the necine moiety.
at m/e 309(C16H2305N), at C-15 and one hydroxy
m/e:337(M+,
293(C17H2703N)
and 222(C13H2002N)
group is located
indicate
fragment
ions
that the ethyl group attached
at C-12 in the necic acid moiety.
m/e:250(12%)
m/e:293(15%)
8%)
-@+!
m/e:l38(56%)
Y
The chemical (acetone), mixed m.p.,
hydrolysis
of Lwith
and IR spectrum
From the data mentioned
m/e:95(100%)
10% KOH in EtOH gave (7R)-retronecine',
[a],,+45.5', which was identical
[a],
m/e:l21(95%)
\
m/e:222(25%)
m/e:309(16%)
j
with the authentic
m.p.115.0-1.16.0"
sample by direct comparison
with
, and the mixture of necic acids.
above,
the structure
of ;was
estimated
to be 15-ethyl-12-hydroxy-
12,13-dimethylsenec-1-enine. The absolute
configurations
X-ray crystallographic pared from EtOH-HBr d=l.l58.
analysis.
solution
of asymmetric The crystals
carbons
in the necic acid moiety were
of yamataimine.HBr
of 1. Recrystallization N
for X-ray analysis
from EtOH gave colorless
revealed
by
were pre-
needles,
m.p.249',
No. 8
769
Crystal
data
of C,8H2705N.HBr reflections monochromated
by the block-diagonal dispersion
results which
of 1 was determined
space group P2,2,2, with four molecules
a=14.888,
The structure
matrix
b=17.092
and c=7.607i.
X-ray diffractometer
(2e1140")
1213 Hkl
by using
was solved by the heavy atom method
least-squares
effect of the bromine
This value was increased
From the experimental
1-enine,
orthorhombic
on a Rigaku four-circle
Cu-Ka radiation(x=1.5418i).
when the anomalous
structure
needles,
in a unit cell of the dimensions
were observed
and was refined
account.
Colorless
:
method
to a final R value of 0.094,
atom for Cu-Ka radiation
to 0.11 if the reversed
absolute
accord with the chemical
was taken into
configuration
result,
the absolute
was assumed. molecular
to be (12S,13R,15S)-15-ethyl-l2-hydroxy-l2,13-dimethylsenec-
as shown in Fig. 1.
Fig. 1
The new necic acid moiety
in yamataimine(1)
sence of ethyl group at C-15 and (S)-configuration pyrrolizidine teresting widely
alkaloids6
from Cacalia
to test the carcinogenic
used as food in the country
activity
are now in progress.
floridana7
activity of Japan.
shows the characteristic
structure
at C-12, being different and C. hastata8.
like as fukinotoxin'
Moreover, because
The tests of cytotoxicity
in the pre-
from the macrocyclic it became just in-
of the genus Cacalia and other biological
No. 8
770
Acknowledgements versity
-
The authors
for the measurement
of the intensity
and this work was supported Education,
Science
thank Professor
data on a Rigaku four-circle
in part by a Grant-in-Aid
and Culture,
H. Ogura and Dr. K. Furuhata
for Cancer
of this Uni-
X-ray diffractometer
Research
from the Ministry
of
Japan.
References
* All melting
points are uncorrected
lution mass spectrometer
and the molecular
and the analytical
formulae were measured
values were good agreement
by high reso-
with the calculated
values. 1.
Part VIII
in the series "Studies
Part VII: M. Hikichi 2.
M. Tanaka,
Japan Analyst,
G. C. Levy and G. L. Nelson, John Wiley
& Sons,
of Crude Drugs".
and T. Furuya, Chem. Pharm. Bull., 3,
S. Toda, T. Nagata,
and H. Kigasawa,
on Constituents
K. Kanida,
See for
3179(1976).
J. Saito, T. Mitsuishi,
S. Hashimoto,
S. Shimizu
21, 41(1972).
"Carbon-13
Nuclear
Magnetic
Resonance
for Organic
Chemist",
New York, Chap.5(1972).
Inc.,
3.
C. C. J. Culvenor,
Tetrahedron
Letters,
1966, 1091.
4.
C. K. Atal,
5.
T. Furuya and M. Hikichi,
Phytochemistry,
6.
T. Furuya and M. Hikichi,
J. Syn. Org. Chem. Japan, 35, 653(1977).
7.
M. P. Cava, K. V. Rao, J. A. Weisbach,
K. K. Kapur, C. C. 3. Culvenor
and L. W. Smith, Tetrahedron
Letters,
1966,
lO_, 2217(1971).
R. F. Raffauf
and B. Douglas,
J. Org. Chem., 33,
3578(1968). 8.
V. S. Konovalov
and G. P. Men'shikov,
Zh. Obsch.
Khim., 15, 328(1945);
Chem. Abst., 40,
3760(1946). K. Hayashi, 9.
A. Natorigawa
T. Furuya and M. Hikichi, I. Hirono,
M. Shimizu,
and H. Mitsuhashi,
Chem. Pharm. Bull., 20, 201(1972).
Chem. Pharm. Bull., 24, 1120(1976).
K. Fushimi,
H. Mori and K. Kato, m,
64, 527(1973).
537
Letters
NO. 8, PP 767 - 770,
1978.
Pargamon
Press.
YAMATAIMINE,A NEW PYRROLIZIDINE FROM CACALIA
School of Pharmaceutical
Sciences,
Kitasato Yoichi
Faculty
of Pharmaceutical
Sciences,
(Received in Japan 5 December 1977;
a new pyrrolizidine
Cacalia yatabei
Maxim.
name
the results of chemical The crude alkaloid
activity
ClBH2705N(M+
are showing
tained by IR spectral responsible spectrum
for two olefinic
of l_shows
protons
geminal methylene
determination
1 is classified rv are at 0.82ppm
(3H, t, J=7.5Hz)
protons
cyclic
337.189),
pyrrolizidine
from the roots of
by discussing
was chromatographed
system to yield
1, colorless
signals of carbons2, carbons,
The signals
of which
(H=l.22ppm)
for Ct13-CH2-C-15, 0.98ppm
macrocyclic
of retronecine4.
767
signals
at
resonance(PMR)
pyrrolizidine
the olefinic
alkaloid.3
proton()C=Ci-)
at C-2,
The signals of the
at 65.52 and 4.30(J=l1.5Hz).
and the coupling alkaloid.
constant
(J=ll.5Hz),
Other assignable
(3H, d, J=8.0Hz)
signals
for Cti3-CH- and 1.18ppm
peaks at 1.25 to 3.50ppm
protons
studies
needles,
at 135.7 and 131.4 are
The proton magnetic
pyrrolizidine
The complicated
on
which are also ascer-
) at C-7 and C-8, respectively.
macrocyclic
mass spectrometric
derivatives
in Compo-
[ol]b8+63.6'(EtOH).
of twelve membered
at C-3, C-5 and C-6 and methine
The high resolution
solvent
in the necine moiety.
of the shift
respectively.
1978)
analysis.
at C-9 appear as a pair of doublet
differences
was isolated
of two ester carbonyl
and >Cl-N<
as a twelve membered
(3H, s) for Ci3-C-12, methylene
(>Cy-OCO-
113 Japan
alkaloids
of yamataimine
at 66.10, 4.98 and 3.85ppm correspond
protons
From the appreciable
pattern
Tokyo,
of pyrrolizidine
-1 KBr at vmax 1720 and 1735cm .
carbons
a typical
The three broad singlets and two methine
the presence
absorption
108 Japan
: yama-taimingasa)
of 1 shows 18 detectable N
spectrum
Bunkyo-ku,
from MeOH ext. of the roots(2.2kg)
m.p. 181-182"(petroleum-acetone),
174.4 and 173.9ppm
of Tokyo,
study and X-ray crystallographic extracted
Tokyo,
Iitaka
silica gel column and eluted with CHCl3-MeOH-NH40H
The I3 C-NMR(CMR)
Minato-ku,
named yamataimine(1)
paper deals with the structural
The present
Furuya*
received in UK for publication 6 Jaa~a~
alkaloid,
(Japanese
Britain.
ALKALOID
University,
University
In the course of the studies on carcinogenic sitae plants,
in Great
YATABEI'
and Tsutomu
Manabu Hikichi
Frinted
are due to the
at C-13 and C-15.
on this alkaloid The fragment
show also a typical macro-
ions at m/e 138(C8H120N),
768
121(C8H,,N)
No. 8
The significant
and 95 (C6HgN 100%) arose from the necine moiety.
at m/e 309(C16H2305N), at C-15 and one hydroxy
m/e:337(M+,
293(C17H2703N)
and 222(C13H2002N)
group is located
indicate
fragment
ions
that the ethyl group attached
at C-12 in the necic acid moiety.
m/e:250(12%)
m/e:293(15%)
8%)
-@+!
m/e:l38(56%)
Y
The chemical (acetone), mixed m.p.,
hydrolysis
of Lwith
and IR spectrum
From the data mentioned
m/e:95(100%)
10% KOH in EtOH gave (7R)-retronecine',
[a],,+45.5', which was identical
[a],
m/e:l21(95%)
\
m/e:222(25%)
m/e:309(16%)
j
with the authentic
m.p.115.0-1.16.0"
sample by direct comparison
with
, and the mixture of necic acids.
above,
the structure
of ;was
estimated
to be 15-ethyl-12-hydroxy-
12,13-dimethylsenec-1-enine. The absolute
configurations
X-ray crystallographic pared from EtOH-HBr d=l.l58.
analysis.
solution
of asymmetric The crystals
carbons
in the necic acid moiety were
of yamataimine.HBr
of 1. Recrystallization N
for X-ray analysis
from EtOH gave colorless
revealed
by
were pre-
needles,
m.p.249',
No. 8
769
Crystal
data
of C,8H2705N.HBr reflections monochromated
by the block-diagonal dispersion
results which
of 1 was determined
space group P2,2,2, with four molecules
a=14.888,
The structure
matrix
b=17.092
and c=7.607i.
X-ray diffractometer
(2e1140")
1213 Hkl
by using
was solved by the heavy atom method
least-squares
effect of the bromine
This value was increased
From the experimental
1-enine,
orthorhombic
on a Rigaku four-circle
Cu-Ka radiation(x=1.5418i).
when the anomalous
structure
needles,
in a unit cell of the dimensions
were observed
and was refined
account.
Colorless
:
method
to a final R value of 0.094,
atom for Cu-Ka radiation
to 0.11 if the reversed
absolute
accord with the chemical
was taken into
configuration
result,
the absolute
was assumed. molecular
to be (12S,13R,15S)-15-ethyl-l2-hydroxy-l2,13-dimethylsenec-
as shown in Fig. 1.
Fig. 1
The new necic acid moiety
in yamataimine(1)
sence of ethyl group at C-15 and (S)-configuration pyrrolizidine teresting widely
alkaloids6
from Cacalia
to test the carcinogenic
used as food in the country
activity
are now in progress.
floridana7
activity of Japan.
shows the characteristic
structure
at C-12, being different and C. hastata8.
like as fukinotoxin'
Moreover, because
The tests of cytotoxicity
in the pre-
from the macrocyclic it became just in-
of the genus Cacalia and other biological
No. 8
770
Acknowledgements versity
-
The authors
for the measurement
of the intensity
and this work was supported Education,
Science
thank Professor
data on a Rigaku four-circle
in part by a Grant-in-Aid
and Culture,
H. Ogura and Dr. K. Furuhata
for Cancer
of this Uni-
X-ray diffractometer
Research
from the Ministry
of
Japan.
References
* All melting
points are uncorrected
lution mass spectrometer
and the molecular
and the analytical
formulae were measured
values were good agreement
by high reso-
with the calculated
values. 1.
Part VIII
in the series "Studies
Part VII: M. Hikichi 2.
M. Tanaka,
Japan Analyst,
G. C. Levy and G. L. Nelson, John Wiley
& Sons,
of Crude Drugs".
and T. Furuya, Chem. Pharm. Bull., 3,
S. Toda, T. Nagata,
and H. Kigasawa,
on Constituents
K. Kanida,
See for
3179(1976).
J. Saito, T. Mitsuishi,
S. Hashimoto,
S. Shimizu
21, 41(1972).
"Carbon-13
Nuclear
Magnetic
Resonance
for Organic
Chemist",
New York, Chap.5(1972).
Inc.,
3.
C. C. J. Culvenor,
Tetrahedron
Letters,
1966, 1091.
4.
C. K. Atal,
5.
T. Furuya and M. Hikichi,
Phytochemistry,
6.
T. Furuya and M. Hikichi,
J. Syn. Org. Chem. Japan, 35, 653(1977).
7.
M. P. Cava, K. V. Rao, J. A. Weisbach,
K. K. Kapur, C. C. 3. Culvenor
and L. W. Smith, Tetrahedron
Letters,
1966,
lO_, 2217(1971).
R. F. Raffauf
and B. Douglas,
J. Org. Chem., 33,
3578(1968). 8.
V. S. Konovalov
and G. P. Men'shikov,
Zh. Obsch.
Khim., 15, 328(1945);
Chem. Abst., 40,
3760(1946). K. Hayashi, 9.
A. Natorigawa
T. Furuya and M. Hikichi, I. Hirono,
M. Shimizu,
and H. Mitsuhashi,
Chem. Pharm. Bull., 20, 201(1972).
Chem. Pharm. Bull., 24, 1120(1976).
K. Fushimi,
H. Mori and K. Kato, m,
64, 527(1973).
537