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Structure of the further norditerpenoids of Podocarpus macrophyllus. Inumakilactone a glucoside, a plant growth inhibitor and inumakilactone E
33,
TetrahedronLetter8No.
STRUCTURE
OF
THE
INUMAKILACTONE
3385
PP
FURTHER
-
1972.
GROWTH
Hayashi
and Hi&hi
of Chemistry,
Tokyo
Yuh Bristol
Research
(Received
in
Podocarpus are potent
compounds of this macrophyllus
D.
communication structures
(Ill)
verified
when
calcd.
490.184,
nagilactone only two
of plant
Don,
inumakilactone
together with
doublets
I with
Eritiill.
INUMAKILACTONE
E
Otsuka,
Tokyo
Ching IIK
Sendai,
South
Road,
determination
Taipei,
Taiwan
for publioation10 July 1972)
cells
A (la)
Japan
Hsl
(3,5,6).
E (7) and inumakilactone
lactones We have
A glucoside,
and nagilactones
of these
1685,
m.p. 1623 and
8400 and 3ZOO cm”];
of three
acetic
with
of I, C,oH&,
vmax (KBr),
(KBr),
hydroxyl
anhydride
no hydroxyl
A diacetate
(%)
University,
and bisnor-diterpenoid
inumakilactone
the structure
spectm
presence
in the signals
with
&eat
(l-S),
some of which
isolated
two
more new
from the stem of
C (&I)
Podocarpus
and F (8).
new compaunds to which
The
present
we assigned
respectively.
and U.V.
The
in
and mitosis
groups [vmox
(2a).
reoeived
of expansion type,
AND
University,
Chung
nor-
J)O nm (e 5608);
hydroxyl
June 1972;
in
Kakisawu’
Pan Chen and Hong-Yen
to produce
deals
i.r.
30
Tohoku
of Taiwan,
Printed
It8
is known
I and VII,
The (EtOH),
Jopen
species
inhibitors
Institute
INHIBITOR
Kyoiku
Sh8 of Chemistry,
Preen.
OF PODOCARPUS MKROPHYLLUS.
A PLANT
Teruo
Department
Per-
NORDITERPENOIDS
A GLUCOSIDE,
Department
33%
(IV) (I&r),
revealing
due to the side in the spectra
groups
The
chains:
of derivatives
1535 cni’],
very
similar
afforded
n.m.r.
their
a I-lactone spectml
signals III,
suggested
the triacetate
are displaced
3385
of
resemblance. of the
[vmax
properties
spectrum (TABLE)
structuml
fvbthyl of
show the presence
in the molecule,
and pyridine
group.
220-22S”,
isopropyl
of an a-pyrone (KBr),
1770 cn?]
II
and
to those of nagilactone
by the molecular
(II),
[hmax
GHS80T0,
is very
Significant group,
in the spectrum
formula
M’
similar
with
differences which of
A
always
was
490.191, that
of
are seen appear as
II by a three-proton
doublet
at 6 1. .2!i and a two-proton
CH2-OAc
is\ evident.
presence
of a hydroxyl
to inumakilactone
3450,
hydroxyl,
large
group at C,
A glucoside
3350,
f-lactone
1780,
1710
chromatogmphy)
n. m. r.
and the
obtained
analyses
was deduced
from
Thence
6 4.15. (A6
1.42
From these
in I.
(VII), and
also
C24H3,0, 1640 co?;
M’
736,
hydrochloride
the
ppm) of l-l,,
physical
presence
of the
group CH3-$H-
upon acetylation
evidences
from the
n. m.r.
A diacetate
in addition
to the signals
Xmax (EtOH),
the
indicates
structure
IX,
spectml major
VII
hydrolysis
C,BH2,0BCl,
has the
with
m.p.
was a glucoside
analysis.
Although
difference
is seen
of glucose
group,
gave
the
I wets assigned
5%-HCI,
the in the
suggesting
revealing
glucose
which
These
of V.
spectral the
on acetylation
254~255’,
(V) by the same reaction. VII
following
222 nm (c 9500),
groupings.
and on mild
that
(VI),
m. p. 296-200~
3,
Glactone
inumakilactoneA
(see TABLE) revealed
of inumakilactone (TABLE),
shift
and a, B-unsatumted 146:
compcund
up-field
at
E.
lnumakilactone v (KBr),
The
multiplet
ws
chemical
The location spectrum
of VIII
chemical
glucosidyl
shifts
at C,5.
the
properties: presence
pentaacetate
(identified identical
by paper with
evidences of the
of yS, The
similar Met6
large
RO I
R=H
III
R=H
V
R=H
II
R=Ac
IV
R=Ac
VI
R=Ac
VII
R=H
VIII
R=Ac
X=CI
X
X=Br
Xl
X=OH
residue to that and
H7
coupling
CH20R
IX
the
and &tailed
glucosidyl
is very
of
3381
No. 33
Comp. Solv.
Mel8 MeP ?6 (Me,,)
TABLE.
N.m.r.
II
IV
V
VII
CDC13
PY
PY
CDC13
Spectm of Pertinent
lnumakilactones and their Derivatives*’
VIII
IX
X
XI
CDC13
CDC13
Py
b
pr
VI
1.45
1.45
1.53
1.50
1.52
1.53
1.60
1.66
1.63
1.38
1.33
1.40
1.35
1.13
1.15
1.95
2.04
1.92
1.25d
1.2ld
1.56d
1.57d
1.4ld
1.33d
1.53d
1.57d
1.59d
(8.0)
(7.0) 1.24d
(6.5)
(6.0)
(6.3)
(6.0)
(6.0)
(6.0)
(6.5)
3.62d
3.62d
3.48*2
3. 46*2
4.95d
5.03d
(4.0)
(4.0)
(3.0)
(2.5)
(7.0) 5.05m
“1
“2
“3
“5 “6
“7
“11
5.10m
*3
*3
3.5ldd (4.0,6.0)
3.52dd (4.0,6.0)
3. 45*2
3.44*2
4.67dd (5.0,3.0)
4.75br
4. 65brf2
*3
*3
4.65d
4.65d
5.46m
5.45m
4. 31d
4.4Obr
4.4Obr
(6.0)
(6.0)
2.83d
(5.0)
1.87d
1.89d
2.13d
2.lOd
2.07d
2.73d
2.70d
(5.0)
(6.0)
(5.5)
(5.0)
(4.8)
(5.0)
(4.5)
(4.5)
(4.5)
5.05m
5.05dd (9.2,6.0)
5. 08*2
*4
4.86dd (4.8,l.J)
4.85dd (5.0,l.O)
5.33dd (4.5,l.S)
5.32dd (4.5,1.5)
5.3ldd (4.5,1.5)
6.25d (10.0)
6.35d
5.08*2
*4
3.99d
4,74d
5.15d
5.16d
(1.0)
(1.5)
(1.5)
5.90
5.83
(9.2)
“14 3.22m
“15
4. 65brf2
2.97sept
(1. J)
2. OOd
5.16d (1.5)
6.73
6.70
6.40
6.35
6.52
6.60
6.75
4.72d
4.52d (10.0)
4.78d
4.4Od
4.73d
4.73d
4.74d
(8.5)
(4.9)
(8.0)
(8.5)
(8.5)
(8.5)
4.13m
*3
4.06d,q (8.0,6.0)
4.35d,q (8.5,6.0)
4.4Obr
4.4Obr
(7.0)
4.974 q (4.9,6.3)
4.15m
“17 cH3co
*l
2.12 2.14
2.00 2.16 2. P
2.06 2. 12
2.00,2.02 2.03,2.10 2.15
Expressed in ppm from TM. Numbers without signal multiplicity Numbers in parentheses ¬e coupling constants.
*2 Chemical
shifts are approximate
because of
*3 Unassignable. *4 The signal overlaps with that of water.
overlapping.
(d, t,m,
etc.)
are singlets.
h
3388
constant
(J=8,
at 4.64
anomeric
hydrogen.
a potent
inhibitor
Thus,
fact
only
original
mentioned
above
that
the
X and Xl, shift
by the
presence
magnitude
into
as well
of halogen
of J2,8 (=5
Hz)
H z ) reveals
H,
+dihydroxy
structure
cells
is only
as of Me28 atoms at Cl,
interpretable
n. m.r. with
the
the
axial
VII
nature
of the
was shown to be
(9). comparisons lN-H2S04
in these hence
at C2 and C8,
discloses
A 15$-glucoside.
on the
ring
when
data
can be reconciled
ring
A in a twisted
of its n.m.r. treatments,
compounds
H8 should
when
boat
be tmns
the
the As
(H2=8,
the the
HB=a).
conformation,
of an epoxide
compounds
conformation
Since
baat
opening
with
significantlyj
of H,.
A of a twisted a tmns
dato
respectively.
vary
the assignment
H2 and
by the
to be a (axial)-orientation
Thus the
considemtian.
le-halo-2a,
of H,,
of Vill
from V by HBr and
in V should be retained
of JT,2(=2.5-8
taken
of plant
was determined
prepared
chemical
reside
as inumakilactone
of IX
explicable
the
was concluded ond division
configurations
While
of glucose
expansion
derivatives
seen in TABLE,
VII
) of H,
of the
The structure corresponding
ppm in CDCIB
33
IX and
as shown
is
X have
in A (10).
References l
To whom all
1) a.
S. lt8,
(1968). 2) a.
Y.
M.
3) a.
Y.
lt8,
Hayashi, M.
6) M.N.
M.
8) Privote
Kodamo,
H.
Y.
Hayashi,
Horn,
J.M.
lmamum and 0.
Jetmhedron
S. Takahashi,
Shimado,
Letters,
Chemistry
1862
(1971).
M.
Suna~wa,
D.H.S.
Horn,
previously
Publication, communication
9) The biological activity Chemistry, C.S. I.R.O.
&
M. S. lt8,
Koreeda M.
and K.
2871
Letters,
(1968).
Comm.,
&hem.
Sasse, Agr.
Comm., Biol.
OS inumakilactone
D (S. It8 and M.
Kodama,
with
(5).
Dr.
Y.
Hoyashi,
Osaka
City
3
S. IM, 2951
M.
’
(lW9).
b. M. N.
253 (1972). Bmsil Cignc,
855 (1971).
Chem.,
1968)
from
b. Ibid.,
An. Acad. 433 (1972).
Nankodo,
ponalactone
2065 91 (1971).
170 (1970).
Experientia,
designated
is identical
Comm.,
849 (1972).
Chem.
c. @,
Nakanishi,
Kodama and J.M.
T&&gdrmqrq,
aem.
H. Ono and T. Sakan,
Sasse and D. Adamson,
Sasse, jb&,
Honda,
Honma and T. Takahashi,
H. Ona and T. Sakan,
K. Hirotsu and A.
D.H.S.
H.
L., K.S. Brown, Jr., T. Nishida, L. J. Durham and A.M. Duffield, M. Silva, M. Haeneisen and P. G. Sammes, Phvtochemistry, L
Galbmith,
TO) lnumakilactone the same part
be addressed.
T. Takahashi,
M.
H. Honma,
T. Sakan,
Kodamo,
7) The compound Special
Sunagawo,
D. H. S. Horn and J.M.
4) W.E.Siinchez s 77 (197). 5) S. lt8,
should
Sunagawa,
S. Takahashi,
Galbmith,
Galbmith,
M.
M.
Sunagawa,
Hayashi,
M. N.
correspondences
Kadamo,
b. 5.
Kodama, c.
the
in press.
Kagaku
no Ryoiki,
University.
test was carried out by courtesy of Dr. M. N. Galbraith ot the Division of Applied to whom wr sincere thanks are due. For method, see (b) and (6).
C (2) also undergoes the epoxide ring cleavage with acids. N.m.r. analysis mvealed structure A in the probcts. M. Sunagawa, M.Sc. Thesis, Tohoku University, 1968.
TetrahedronLetter8No.
STRUCTURE
OF
THE
INUMAKILACTONE
3385
PP
FURTHER
-
1972.
GROWTH
Hayashi
and Hi&hi
of Chemistry,
Tokyo
Yuh Bristol
Research
(Received
in
Podocarpus are potent
compounds of this macrophyllus
D.
communication structures
(Ill)
verified
when
calcd.
490.184,
nagilactone only two
of plant
Don,
inumakilactone
together with
doublets
I with
Eritiill.
INUMAKILACTONE
E
Otsuka,
Tokyo
Ching IIK
Sendai,
South
Road,
determination
Taipei,
Taiwan
for publioation10 July 1972)
cells
A (la)
Japan
Hsl
(3,5,6).
E (7) and inumakilactone
lactones We have
A glucoside,
and nagilactones
of these
1685,
m.p. 1623 and
8400 and 3ZOO cm”];
of three
acetic
with
of I, C,oH&,
vmax (KBr),
(KBr),
hydroxyl
anhydride
no hydroxyl
A diacetate
(%)
University,
and bisnor-diterpenoid
inumakilactone
the structure
spectm
presence
in the signals
with
&eat
(l-S),
some of which
isolated
two
more new
from the stem of
C (&I)
Podocarpus
and F (8).
new compaunds to which
The
present
we assigned
respectively.
and U.V.
The
in
and mitosis
groups [vmox
(2a).
reoeived
of expansion type,
AND
University,
Chung
nor-
J)O nm (e 5608);
hydroxyl
June 1972;
in
Kakisawu’
Pan Chen and Hong-Yen
to produce
deals
i.r.
30
Tohoku
of Taiwan,
Printed
It8
is known
I and VII,
The (EtOH),
Jopen
species
inhibitors
Institute
INHIBITOR
Kyoiku
Sh8 of Chemistry,
Preen.
OF PODOCARPUS MKROPHYLLUS.
A PLANT
Teruo
Department
Per-
NORDITERPENOIDS
A GLUCOSIDE,
Department
33%
(IV) (I&r),
revealing
due to the side in the spectra
groups
The
chains:
of derivatives
1535 cni’],
very
similar
afforded
n.m.r.
their
a I-lactone spectml
signals III,
suggested
the triacetate
are displaced
3385
of
resemblance. of the
[vmax
properties
spectrum (TABLE)
structuml
fvbthyl of
show the presence
in the molecule,
and pyridine
group.
220-22S”,
isopropyl
of an a-pyrone (KBr),
1770 cn?]
II
and
to those of nagilactone
by the molecular
(II),
[hmax
GHS80T0,
is very
Significant group,
in the spectrum
formula
M’
similar
with
differences which of
A
always
was
490.191, that
of
are seen appear as
II by a three-proton
doublet
at 6 1. .2!i and a two-proton
CH2-OAc
is\ evident.
presence
of a hydroxyl
to inumakilactone
3450,
hydroxyl,
large
group at C,
A glucoside
3350,
f-lactone
1780,
1710
chromatogmphy)
n. m. r.
and the
obtained
analyses
was deduced
from
Thence
6 4.15. (A6
1.42
From these
in I.
(VII), and
also
C24H3,0, 1640 co?;
M’
736,
hydrochloride
the
ppm) of l-l,,
physical
presence
of the
group CH3-$H-
upon acetylation
evidences
from the
n. m.r.
A diacetate
in addition
to the signals
Xmax (EtOH),
the
indicates
structure
IX,
spectml major
VII
hydrolysis
C,BH2,0BCl,
has the
with
m.p.
was a glucoside
analysis.
Although
difference
is seen
of glucose
group,
gave
the
I wets assigned
5%-HCI,
the in the
suggesting
revealing
glucose
which
These
of V.
spectral the
on acetylation
254~255’,
(V) by the same reaction. VII
following
222 nm (c 9500),
groupings.
and on mild
that
(VI),
m. p. 296-200~
3,
Glactone
inumakilactoneA
(see TABLE) revealed
of inumakilactone (TABLE),
shift
and a, B-unsatumted 146:
compcund
up-field
at
E.
lnumakilactone v (KBr),
The
multiplet
ws
chemical
The location spectrum
of VIII
chemical
glucosidyl
shifts
at C,5.
the
properties: presence
pentaacetate
(identified identical
by paper with
evidences of the
of yS, The
similar Met6
large
RO I
R=H
III
R=H
V
R=H
II
R=Ac
IV
R=Ac
VI
R=Ac
VII
R=H
VIII
R=Ac
X=CI
X
X=Br
Xl
X=OH
residue to that and
H7
coupling
CH20R
IX
the
and &tailed
glucosidyl
is very
of
3381
No. 33
Comp. Solv.
Mel8 MeP ?6 (Me,,)
TABLE.
N.m.r.
II
IV
V
VII
CDC13
PY
PY
CDC13
Spectm of Pertinent
lnumakilactones and their Derivatives*’
VIII
IX
X
XI
CDC13
CDC13
Py
b
pr
VI
1.45
1.45
1.53
1.50
1.52
1.53
1.60
1.66
1.63
1.38
1.33
1.40
1.35
1.13
1.15
1.95
2.04
1.92
1.25d
1.2ld
1.56d
1.57d
1.4ld
1.33d
1.53d
1.57d
1.59d
(8.0)
(7.0) 1.24d
(6.5)
(6.0)
(6.3)
(6.0)
(6.0)
(6.0)
(6.5)
3.62d
3.62d
3.48*2
3. 46*2
4.95d
5.03d
(4.0)
(4.0)
(3.0)
(2.5)
(7.0) 5.05m
“1
“2
“3
“5 “6
“7
“11
5.10m
*3
*3
3.5ldd (4.0,6.0)
3.52dd (4.0,6.0)
3. 45*2
3.44*2
4.67dd (5.0,3.0)
4.75br
4. 65brf2
*3
*3
4.65d
4.65d
5.46m
5.45m
4. 31d
4.4Obr
4.4Obr
(6.0)
(6.0)
2.83d
(5.0)
1.87d
1.89d
2.13d
2.lOd
2.07d
2.73d
2.70d
(5.0)
(6.0)
(5.5)
(5.0)
(4.8)
(5.0)
(4.5)
(4.5)
(4.5)
5.05m
5.05dd (9.2,6.0)
5. 08*2
*4
4.86dd (4.8,l.J)
4.85dd (5.0,l.O)
5.33dd (4.5,l.S)
5.32dd (4.5,1.5)
5.3ldd (4.5,1.5)
6.25d (10.0)
6.35d
5.08*2
*4
3.99d
4,74d
5.15d
5.16d
(1.0)
(1.5)
(1.5)
5.90
5.83
(9.2)
“14 3.22m
“15
4. 65brf2
2.97sept
(1. J)
2. OOd
5.16d (1.5)
6.73
6.70
6.40
6.35
6.52
6.60
6.75
4.72d
4.52d (10.0)
4.78d
4.4Od
4.73d
4.73d
4.74d
(8.5)
(4.9)
(8.0)
(8.5)
(8.5)
(8.5)
4.13m
*3
4.06d,q (8.0,6.0)
4.35d,q (8.5,6.0)
4.4Obr
4.4Obr
(7.0)
4.974 q (4.9,6.3)
4.15m
“17 cH3co
*l
2.12 2.14
2.00 2.16 2. P
2.06 2. 12
2.00,2.02 2.03,2.10 2.15
Expressed in ppm from TM. Numbers without signal multiplicity Numbers in parentheses ¬e coupling constants.
*2 Chemical
shifts are approximate
because of
*3 Unassignable. *4 The signal overlaps with that of water.
overlapping.
(d, t,m,
etc.)
are singlets.
h
3388
constant
(J=8,
at 4.64
anomeric
hydrogen.
a potent
inhibitor
Thus,
fact
only
original
mentioned
above
that
the
X and Xl, shift
by the
presence
magnitude
into
as well
of halogen
of J2,8 (=5
Hz)
H z ) reveals
H,
+dihydroxy
structure
cells
is only
as of Me28 atoms at Cl,
interpretable
n. m.r. with
the
the
axial
VII
nature
of the
was shown to be
(9). comparisons lN-H2S04
in these hence
at C2 and C8,
discloses
A 15$-glucoside.
on the
ring
when
data
can be reconciled
ring
A in a twisted
of its n.m.r. treatments,
compounds
H8 should
when
boat
be tmns
the
the As
(H2=8,
the the
HB=a).
conformation,
of an epoxide
compounds
conformation
Since
baat
opening
with
significantlyj
of H,.
A of a twisted a tmns
dato
respectively.
vary
the assignment
H2 and
by the
to be a (axial)-orientation
Thus the
considemtian.
le-halo-2a,
of H,,
of Vill
from V by HBr and
in V should be retained
of JT,2(=2.5-8
taken
of plant
was determined
prepared
chemical
reside
as inumakilactone
of IX
explicable
the
was concluded ond division
configurations
While
of glucose
expansion
derivatives
seen in TABLE,
VII
) of H,
of the
The structure corresponding
ppm in CDCIB
33
IX and
as shown
is
X have
in A (10).
References l
To whom all
1) a.
S. lt8,
(1968). 2) a.
Y.
M.
3) a.
Y.
lt8,
Hayashi, M.
6) M.N.
M.
8) Privote
Kodamo,
H.
Y.
Hayashi,
Horn,
J.M.
lmamum and 0.
Jetmhedron
S. Takahashi,
Shimado,
Letters,
Chemistry
1862
(1971).
M.
Suna~wa,
D.H.S.
Horn,
previously
Publication, communication
9) The biological activity Chemistry, C.S. I.R.O.
&
M. S. lt8,
Koreeda M.
and K.
2871
Letters,
(1968).
Comm.,
&hem.
Sasse, Agr.
Comm., Biol.
OS inumakilactone
D (S. It8 and M.
Kodama,
with
(5).
Dr.
Y.
Hoyashi,
Osaka
City
3
S. IM, 2951
M.
’
(lW9).
b. M. N.
253 (1972). Bmsil Cignc,
855 (1971).
Chem.,
1968)
from
b. Ibid.,
An. Acad. 433 (1972).
Nankodo,
ponalactone
2065 91 (1971).
170 (1970).
Experientia,
designated
is identical
Comm.,
849 (1972).
Chem.
c. @,
Nakanishi,
Kodama and J.M.
T&&gdrmqrq,
aem.
H. Ono and T. Sakan,
Sasse and D. Adamson,
Sasse, jb&,
Honda,
Honma and T. Takahashi,
H. Ona and T. Sakan,
K. Hirotsu and A.
D.H.S.
H.
L., K.S. Brown, Jr., T. Nishida, L. J. Durham and A.M. Duffield, M. Silva, M. Haeneisen and P. G. Sammes, Phvtochemistry, L
Galbmith,
TO) lnumakilactone the same part
be addressed.
T. Takahashi,
M.
H. Honma,
T. Sakan,
Kodamo,
7) The compound Special
Sunagawo,
D. H. S. Horn and J.M.
4) W.E.Siinchez s 77 (197). 5) S. lt8,
should
Sunagawa,
S. Takahashi,
Galbmith,
Galbmith,
M.
M.
Sunagawa,
Hayashi,
M. N.
correspondences
Kadamo,
b. 5.
Kodama, c.
the
in press.
Kagaku
no Ryoiki,
University.
test was carried out by courtesy of Dr. M. N. Galbraith ot the Division of Applied to whom wr sincere thanks are due. For method, see (b) and (6).
C (2) also undergoes the epoxide ring cleavage with acids. N.m.r. analysis mvealed structure A in the probcts. M. Sunagawa, M.Sc. Thesis, Tohoku University, 1968.