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Daphniteijsmanine, the daphniphyllum alkaloid with a new ketal moiety
Tetrahedron
DAPHNITEIJSMANINE,
Printed
Pergamon PNea.
NO. 42, pp 3673-3676, 1974.
I&tore
in Great Rritaln.
THE DAPHNIPHYLLUM ALKALOID WITH A NEW KETAL MOIETY
Shosuke Yamamura* Faculty
of
Pharmacy,
Meijo
University,
Showa-ku,
Nagoya,
Japan
and Yoshimasa Chemical
Our biosynthetic biosynthesized
studies
from six
us demonstrate
estimated
isolation
molecules
Nagoya,
Japan
of
collected
a viscous
oil,
idea.
secodaphniphylline
[I) (II)
of
with
into
the fruits
crystalline
solid
they
intermediate,
the important
moiety
earlier,
of the plant
with
(10
m.p.
components
separated
: 10 : l)]
a small
amount of
EtOAc);
C30H4903N;m/e 471(M+), 456, 454, 440, 428, 286 and 216; Y,,(Nujol)
(III).
teijsmanii
was further
60 PF254 in n-hexane-Et20-Et2NH
the
with AcOEt gave
Elution
oil
’
acetate
Uaphniphyllum
This
(I),
inter-
the alkaloidal
on alumina.
daphniteijsmanine
and one of
together
N-acetyldaphniteijsmanine
spots.
are
we wish to describe
a new ketal
and chromatographed
of
that
to daphniphylline,
for
paper,
as reported
TLC showed several
TLC [Kieselgel
a squalene-like
In the present
the same procedure
whose analytical
-via
pathway from squalene
daphniteijsmanine
in Yakushima‘,
preparative
acid
have revealed
have been made to search
from the MeOH extracts
Zollinger
repeated
of
to essentially
were obtained
efforts
from the above
conversion
According
Chikusa-ku,
alkaloids
of mevalonic
biosynthetic
Further
and structure
chemical
on the daphniphyllum
a possible 1
the C30 -alkaloids. mediates
Nagoya University,
im Japmm 13 Augurt 1974; rooeived is UK for publioation 3 September 1974)
(Received
let
Institute,
Hirata
228-232*
by
to afford
(from -n-hexane3450br.cm-1
and
no C=O. From the NW (see daphniteijsmanine daphniphylline containing
(I)
of
and mass spectra
(g0.76,
must have the same nitrogen
(II)3.
moiety
have two methyl
The Table)
However,
the remarkable
the structure,
singlets
(I,
$1.12
heterocyclic
difference
as follows. and 1.48;
0.92,
is
Although II,
50.89
3673
the
0.94,
2.54
skeleton
and 3.06;
as that
of
m/e 286), seco-
seen in the non-nitrogen alkaloids
and 1.42),
(I)
the former
and (II)
both
has the NMR
3674
No. 42
signal
at f3.42(2H,
s)
due to a hydroxymethyl
group,
on acetylation
with Ac20-pyridine
acetate
C34H5305N; m/e 555(M+) and 328; Ymax(film)
(III),
0.77(3H,
d, J= 6Hz),
2.14(3H,
s),
4.36(1H,
m).
4.08)
0.80(3H,
3.38(123,
s),
l.l4(3H,
dd, J= 8,5Hz),
In the NMR spectrum
are due to two protons
consideration, degradation
(room temp.,
which is
product
(IV)
of
(I)
I (or
giving
l.l5(3H, br.s),
III],
1745 and 1643cm-l; d, J= 6Hz),
3.53(1H,
seems to have a ketal
The NMR spectra
for
1.48(3H,
at G.37
of
s),
with
2.07(3H,
4.08(1H,
and 4.22
grouping
its
br.s)
s(CDC13)4
d, J= 4.5Hz),
two signals
except
to S3.80(2H,
N-acetyldaphniteijsmanine
From the above data coupled
of daphniphylline5
The Table.
0.76
s),
3.80(2H,
(-CE-0-).
daphniteijsmanine
overnight)
shifted
s),
m) and
(c3.38
and
a biogenetic
similar
to that
stereochemistry
(see
of the
The Table).
I and IV.’
(3H, s)
0.92
(3H, d, J = 6.2Hz)
0.94
(3H, d, J = 6.2Hz)
1.12
(3H, s)
0.74
(3H, s)
1.48
(3H, s)
1.46
(3H, s)
2.54
(lH,
d, J = 4.4Hz)
3.06
(lH,
br.s)
3.37
(lH,
dd, J = 8.0,
3.40
(IH,
d, J = 12Hz)
3.65
(lH,
d, J = 12Hz)
5.OHz)
3.42
(2H, s)
3.78
(2H, br.s)
4.22
(lH,
4.18
(lH,
m)
m)
* In CDC13.
From a comparison at the carbon addition,
of the NMRspectra
atom bearing
the proton
(I)
was confirmed
with
the corresponding
heated
in AcOH at 110’
condition
3
for
enough to cleave
(VI)
y,,(Nujol)
4.5hr, a ketal
the
is is
at $3.37
conformation.
chemical
was reduced
hydroxy-compound
217O; C32H5104N (m/e 513(M+));
groups
to the NMRsignal the most stable
(V)
I and IV, it
and hydroxyl
by the following
N-Acetylsecodaphniphylline give
methyl
corresponding
shown in the structure thus obtained
both
between
with
in VI.
different is
the stereochemistry In
to each other.
in an&configuration,
Finally,
as
the structure
NaBH4 in THF (room temp.,
3480 and 1640cm-l;
ring
that
(I)
evidences.
as a main product
compound (VI)
clear
(in
This fact
72% yield),
~(CDCl,)
was recovered
overnight)
4.06(1H,
in spite
may be attributable
m.p. m).
to
216When
of a vigourous to an un-
lio.
3675
42
(I)
R = H
(III)
R = AC
CH20H
(IV)
(VI) R = H
(VI :) R = MS favourable
configuration
with mesyl
chloride-pyridine
mesylate
(VII),
3.10(3H,
s)
above
(llO’,
(Ill),
*a
of the newly formed hydroxyl. (room temp.,
2.5hr)
m/e 495(M+- MeS03H); y,,
and 5.47(18, 4.5hr)
m).
When treated
,6 the mesylate
plausible
(film)
intermediate
(VII)
group.
to give 1640,
Thus, VI was further
a viscous
1360br.
oil
of
the corresponding
and 1335sh.cm -l;
with AcOH under the same condition was converted
(VIII),
into
in 28% yield
treated
s(coc1,) as described
N-acetyldaphniteijsmanine
acetate
(TLC, IR, NMRand mass spectra).
(VII)
-
(III)
. (VIII) R = H or AC; X: Amine moiety.
From a biogenetic of
triterpenoids
point as well
of view,
the present
as of triterpene
studies
alkaloids
showed a novel
(see
The Scheme)‘.
example
in the field
3676
The Scheme.
Biogenesis
of the non-nitrogen
containing
moiety
of the alkaloids.
or HO
SQUALENE
HO
/ ‘\ I DAPHMACRINE7
CH20H
J
CH20H 1
IH20H SECODAPHNIPHYLLINE R
The authors measurements
: Amine moiety or polyene.
DAPHNITEIJSMANINE
wish to thank Drs. M. Kurono and M. Toda (One Pharmaceutical of
the high resolution
Co. Ltd.)
for
mass spectra.
REFERENCESAND FOOTNOTES Letters 1. K.T. Suzuki, S. Okuda, H. Niwa, M. Toda, Y. Hirata and S. Yamamura, Tetrahedron 799 (1973). 2. S. Yamamura and Y. Hirata, Tetrahedron Letters in press (1974). 3. M. Toda, Y. Hirata and S. Yamamura, Tetrahedron 8, 1477 (1972). 4. Two signals at 83.53 and 4.36 can be assigned to two protons attached to the carbon atoms bearing the N-AC group, as found in the case of N-acetylsecodaphniphylline (V). 5. The ketal acid, an oxidation product of daphniphylline, was treated with excess diazomethane in Et20 , and then reduced with LiAlH4 in THF to give IV (H. Irikawa, N. Sakabe, S. Yamamura and Y. Hirata, Tetrahedron 24, 5691 (1968). 6. An olefin [C32H4903N; m/e 495(hi*); Hnax(Nujol) 1645cm -1; g(CDC13) 5.42-5.96(2H, complex)] has been also obtained in 27% yield. Chem. Commun. 600 (1968). 7. T. Nakano, Y. Saeki, C.S. Gibbons and J. Trotter,
DAPHNITEIJSMANINE,
Printed
Pergamon PNea.
NO. 42, pp 3673-3676, 1974.
I&tore
in Great Rritaln.
THE DAPHNIPHYLLUM ALKALOID WITH A NEW KETAL MOIETY
Shosuke Yamamura* Faculty
of
Pharmacy,
Meijo
University,
Showa-ku,
Nagoya,
Japan
and Yoshimasa Chemical
Our biosynthetic biosynthesized
studies
from six
us demonstrate
estimated
isolation
molecules
Nagoya,
Japan
of
collected
a viscous
oil,
idea.
secodaphniphylline
[I) (II)
of
with
into
the fruits
crystalline
solid
they
intermediate,
the important
moiety
earlier,
of the plant
with
(10
m.p.
components
separated
: 10 : l)]
a small
amount of
EtOAc);
C30H4903N;m/e 471(M+), 456, 454, 440, 428, 286 and 216; Y,,(Nujol)
(III).
teijsmanii
was further
60 PF254 in n-hexane-Et20-Et2NH
the
with AcOEt gave
Elution
oil
’
acetate
Uaphniphyllum
This
(I),
inter-
the alkaloidal
on alumina.
daphniteijsmanine
and one of
together
N-acetyldaphniteijsmanine
spots.
are
we wish to describe
a new ketal
and chromatographed
of
that
to daphniphylline,
for
paper,
as reported
TLC showed several
TLC [Kieselgel
a squalene-like
In the present
the same procedure
whose analytical
-via
pathway from squalene
daphniteijsmanine
in Yakushima‘,
preparative
acid
have revealed
have been made to search
from the MeOH extracts
Zollinger
repeated
of
to essentially
were obtained
efforts
from the above
conversion
According
Chikusa-ku,
alkaloids
of mevalonic
biosynthetic
Further
and structure
chemical
on the daphniphyllum
a possible 1
the C30 -alkaloids. mediates
Nagoya University,
im Japmm 13 Augurt 1974; rooeived is UK for publioation 3 September 1974)
(Received
let
Institute,
Hirata
228-232*
by
to afford
(from -n-hexane3450br.cm-1
and
no C=O. From the NW (see daphniteijsmanine daphniphylline containing
(I)
of
and mass spectra
(g0.76,
must have the same nitrogen
(II)3.
moiety
have two methyl
The Table)
However,
the remarkable
the structure,
singlets
(I,
$1.12
heterocyclic
difference
as follows. and 1.48;
0.92,
is
Although II,
50.89
3673
the
0.94,
2.54
skeleton
and 3.06;
as that
of
m/e 286), seco-
seen in the non-nitrogen alkaloids
and 1.42),
(I)
the former
and (II)
both
has the NMR
3674
No. 42
signal
at f3.42(2H,
s)
due to a hydroxymethyl
group,
on acetylation
with Ac20-pyridine
acetate
C34H5305N; m/e 555(M+) and 328; Ymax(film)
(III),
0.77(3H,
d, J= 6Hz),
2.14(3H,
s),
4.36(1H,
m).
4.08)
0.80(3H,
3.38(123,
s),
l.l4(3H,
dd, J= 8,5Hz),
In the NMR spectrum
are due to two protons
consideration, degradation
(room temp.,
which is
product
(IV)
of
(I)
I (or
giving
l.l5(3H, br.s),
III],
1745 and 1643cm-l; d, J= 6Hz),
3.53(1H,
seems to have a ketal
The NMR spectra
for
1.48(3H,
at G.37
of
s),
with
2.07(3H,
4.08(1H,
and 4.22
grouping
its
br.s)
s(CDC13)4
d, J= 4.5Hz),
two signals
except
to S3.80(2H,
N-acetyldaphniteijsmanine
From the above data coupled
of daphniphylline5
The Table.
0.76
s),
3.80(2H,
(-CE-0-).
daphniteijsmanine
overnight)
shifted
s),
m) and
(c3.38
and
a biogenetic
similar
to that
stereochemistry
(see
of the
The Table).
I and IV.’
(3H, s)
0.92
(3H, d, J = 6.2Hz)
0.94
(3H, d, J = 6.2Hz)
1.12
(3H, s)
0.74
(3H, s)
1.48
(3H, s)
1.46
(3H, s)
2.54
(lH,
d, J = 4.4Hz)
3.06
(lH,
br.s)
3.37
(lH,
dd, J = 8.0,
3.40
(IH,
d, J = 12Hz)
3.65
(lH,
d, J = 12Hz)
5.OHz)
3.42
(2H, s)
3.78
(2H, br.s)
4.22
(lH,
4.18
(lH,
m)
m)
* In CDC13.
From a comparison at the carbon addition,
of the NMRspectra
atom bearing
the proton
(I)
was confirmed
with
the corresponding
heated
in AcOH at 110’
condition
3
for
enough to cleave
(VI)
y,,(Nujol)
4.5hr, a ketal
the
is is
at $3.37
conformation.
chemical
was reduced
hydroxy-compound
217O; C32H5104N (m/e 513(M+));
groups
to the NMRsignal the most stable
(V)
I and IV, it
and hydroxyl
by the following
N-Acetylsecodaphniphylline give
methyl
corresponding
shown in the structure thus obtained
both
between
with
in VI.
different is
the stereochemistry In
to each other.
in an&configuration,
Finally,
as
the structure
NaBH4 in THF (room temp.,
3480 and 1640cm-l;
ring
that
(I)
evidences.
as a main product
compound (VI)
clear
(in
This fact
72% yield),
~(CDCl,)
was recovered
overnight)
4.06(1H,
in spite
may be attributable
m.p. m).
to
216When
of a vigourous to an un-
lio.
3675
42
(I)
R = H
(III)
R = AC
CH20H
(IV)
(VI) R = H
(VI :) R = MS favourable
configuration
with mesyl
chloride-pyridine
mesylate
(VII),
3.10(3H,
s)
above
(llO’,
(Ill),
*a
of the newly formed hydroxyl. (room temp.,
2.5hr)
m/e 495(M+- MeS03H); y,,
and 5.47(18, 4.5hr)
m).
When treated
,6 the mesylate
plausible
(film)
intermediate
(VII)
group.
to give 1640,
Thus, VI was further
a viscous
1360br.
oil
of
the corresponding
and 1335sh.cm -l;
with AcOH under the same condition was converted
(VIII),
into
in 28% yield
treated
s(coc1,) as described
N-acetyldaphniteijsmanine
acetate
(TLC, IR, NMRand mass spectra).
(VII)
-
(III)
. (VIII) R = H or AC; X: Amine moiety.
From a biogenetic of
triterpenoids
point as well
of view,
the present
as of triterpene
studies
alkaloids
showed a novel
(see
The Scheme)‘.
example
in the field
3676
The Scheme.
Biogenesis
of the non-nitrogen
containing
moiety
of the alkaloids.
or HO
SQUALENE
HO
/ ‘\ I DAPHMACRINE7
CH20H
J
CH20H 1
IH20H SECODAPHNIPHYLLINE R
The authors measurements
: Amine moiety or polyene.
DAPHNITEIJSMANINE
wish to thank Drs. M. Kurono and M. Toda (One Pharmaceutical of
the high resolution
Co. Ltd.)
for
mass spectra.
REFERENCESAND FOOTNOTES Letters 1. K.T. Suzuki, S. Okuda, H. Niwa, M. Toda, Y. Hirata and S. Yamamura, Tetrahedron 799 (1973). 2. S. Yamamura and Y. Hirata, Tetrahedron Letters in press (1974). 3. M. Toda, Y. Hirata and S. Yamamura, Tetrahedron 8, 1477 (1972). 4. Two signals at 83.53 and 4.36 can be assigned to two protons attached to the carbon atoms bearing the N-AC group, as found in the case of N-acetylsecodaphniphylline (V). 5. The ketal acid, an oxidation product of daphniphylline, was treated with excess diazomethane in Et20 , and then reduced with LiAlH4 in THF to give IV (H. Irikawa, N. Sakabe, S. Yamamura and Y. Hirata, Tetrahedron 24, 5691 (1968). 6. An olefin [C32H4903N; m/e 495(hi*); Hnax(Nujol) 1645cm -1; g(CDC13) 5.42-5.96(2H, complex)] has been also obtained in 27% yield. Chem. Commun. 600 (1968). 7. T. Nakano, Y. Saeki, C.S. Gibbons and J. Trotter,