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Synthesis and mechanism of formation of novel tricyclic nucleosides, 3-β-d-ribofuranosylpyrazolo[3,2-i purine derivatives, by a one-step reaction of 6-enaminopurine with hydrazine
Tetrahcdron Letter~, Vol.32, No.50, pp 7415-74!8, 1991 Printed in Great Britain
SYNTHESIS
AND MECHANISM
0040-4039/91 $3.00 + .00 Pergamon Press plc
OF FORMATION
OF NOVEL TRICYCLIC
3-~-D-RIBOFURANOSYLPYRAZOLO[3,2-!]PURINE ONE-STEP REACTION OF 6-ENAMINOPURINE
Norimitsu School
1-5-8,
DERIVATIVES, BY A WITH HYDRAZINE
Hamamichi I
of Pharmaceutical
Hatanodai
NUCLEOSIDES,
Sciences,
Shinagawa-ku,
Showa University,
Tokyo
142, Japan
Summary: Ethyl 3-~-D-ribofuranosylpyrazolo[3,2-!]purine-9-carboxylate (8) has been prepared from a fully protected 6-chloropurine derivative in four steps including a one-step reaction for the preparation of 3-~-D-ribofuranosyl[3,2-i]purine derivative 5 by 6-enaminopurine and hydrazine, and the mechanism of formation of 5 is discussed.
Polycyclic and pyrimidines binding pounds
nucleosides
with five- or six-membered
are an important
class
sites, 2 base-pair mismatches are known to exhibit
of compounds
a new kind of antitumor
In this paper the synthesis
and mechanism
derivatives,
from enamino-ester
by a one-step
Reaction
novel
and biological of novel
of formation tricyclic
reaction
of enzyme-
these comtricyclic
of 3-~-D-
nucleosides,
are described.
of 6-chloro-9-[2,3-O-isopropylidene-5-O-(2-tetrahydropyranyl)-
~-D-ribofuranosyl]purine DMF at room temperature
(1) 5 with ethyl gave 2 [solid;
cyanoacetate
IR (KBr):
(CO) cm-l; UV ~ max MeOH (g): 339 (34000), (Chart
activity
the synthesis
ribofuranosylpyrazolo[3,2-!]purine 3 and hydrazine
for the studies
of oligonucleotides. 3 Also,
activity.4 Much attention has been paid toward nucleosides.
rings fused to purines
I). Catalytic
hydrogenation
v/v) under medium pressure
3100
using sodium hydride (NH),
328 (sh, 29500)
2200 nm]
(CN),
in 85% yield
of 2 with 5% Pd-C in benzene-DMF
(I : i,
(4 atm) gave ethyl @-(aminomethylene)-9-[2,3-O-iso-
propylidene-5-(2-tetrahydropyranyl)-~-D-ribofuranosyl]purine-6-acetate [solid;
IR (KBr):
(11300), (KBr):
3400
263 (i1500),
2930,
28% yield.
(NH),
pyridine-ethanol
(~):
268 (6100),
nm]
UVNmax
1670 (CO) cm-l;
in 71% yield, MeOH
of 3 with hydrazine
(k):
UV X m a x MeOH
246 (7100),
sulfate
(~):
derivative 319 (sh,
ed with diazomethane
230 (19000),
66 [solid;
262 (8700) nm]
or hydrochloride
11900),
287 (15000)
FeCI 3 test:
341 (17800)
to give 7 [solid;
UV~max
7415
nm]
(3) (6):
236
together with 4 [solid;
(i : i, v/v) at 100°C for 3 h gave 5 [foam;
(CO) cm-l; U V x max MeOH with pyrazolone
3310 (NH),
320 (17000)
1735 (CO) cm-l;
Reaction
in
1655
nm]
in
(3 equiv.)
IR (KBr):
IR in
1700
in 86% yield along
green color;
UV ~ max MeOH
in 8% yield,
which was treat-
MeOH (~):
230 (sh, 7100),
300
7416
(17600),
310 (sh, 15700) nm]. Alternatively,
anol under reflux the products respectively.
Removal
with hydrazine
5 and 6 were obtained
of the protecting
groups
monohydrate
in 40% and 43% yields,
of 5 with trifluoroacetic
gave ethyl
3-~-D-ribofuranosylpyrazolo[3,2-!Jpurine-9-carboxylate
182-184°C;
fluorescence
kmax
emission:
233 nm; ~F=0"407 ] in 84%o yield. matic region appeared
at~ 8.57
tricyclic
ring appeared structure
that tricyclic derivative treatment
ring-opening
dec.;
upon ~Ikali
a pyrazolo
UV~max
MeOH
and hydrolysis
(~):
five-membered
the protecting
to give the amide fluorescence reaction
MeOH
groups
and 146.8
of 3 with hydrazine,
fluorescence
compound
the hydrszino
of 3 with dimethyl MS m/z:
532 (M+),
hydrazine
518 (M+),
(Scheme
derivative zine
it seems
6 is obtained
that first an addition
of
indicates
C-6 and N-I.
elimination
of
12, whose hydrazino
C-6 and N-I is cleaved
by cyclization
deriv-
The structure
spectroscopy. 13 This result
to 5 with elimination
which
the imidazole
to give the spiro intermediate
the linkage between which cyelizes
at 100°C
of 3 with methylhydra-
group of 3 takes place to give
at the C-6 carbon
I). Then,
Reaction
moiety of the purine ring is cleaved between
On the basis of these results
FABMS m/z:
for 2.5 h gave
in 80% yield,
262 (B + I)] was obtained.
by IH-NMR and 13C-NMR
acid
After brief
in ethanol
276 (B + i)]
to 5 by heating
zole derivative,
in ethanol.
gave
in 87%
that 12 is an intermediate
at 50°C for 20 h did not give 5, instead
to the enamine
of NMR to be
392 nm;
12 [solid;
of 12 in ethanol
zine 12 in ethanol
attacks
nm]
as follows.
was not converted
hydrazine
the
of 5 with ammonia
~ max emission:
This indicates
gave the adduct
MS m/z:
9
Also,
in 80% yield.
derivative
Heating
for both 5 and 6. Reaction
moiety
The
product
5 appears
287 (14800)
of 5 was elucidated
in 30% yield.
13 [solid;
in 58% yield.
Reaction
232 (21700),
236 nm; ~F=0.40J
5 in 53% yield and 6 in 25% yield.
that the pyrimidine
(C-8).
of which were removed using trifluoroacetic
of formation
14 was established
(s, IH,
to give 5, On the basis
ring,
nucleoside.
(~):
Ii [mp 206-208°C,
505 (MH+)] was isolated
ative 14 [solid;
and 9.57
ring I0 fused to
gave the ring-opened
orthoformate
tricyclic
k max excitation:
The mechanism
(C-9a)
293 (6900) nm]
of the pyrimidine
the amide i0 [foam; U V ~ m a x yield,
of pyrazole
treatment II and, as expected,
sodium hydroxide
ester 9 was cyclized with triethyl spectroscopy
137.4
by
of 8 in the aro-
confirmed by a chemical method. It is known such as N 6 -ethenoadenosine and pyrimido[2,l-i]purine
of 5 with aqueous
[mp 132-134°C
(DMSO-d6)
was further
compounds
undergo
(C-9),
acid
[mp
N max excitation:
8.71 (s, IH, H-2)
of 89, the carbons
at~ 103.6
(8)
of 5 and 8 were established
The IH~NMR signals (s, IH, H-5),
H-8) 8. In the 13C-NMR spectrum pyrimidine
384 nm; fluorescence
The structures
IH-NMR and 13C-NMR spectroscopy.
in eth-
[path a]
to give the pyra-
of ammonia.
Pyrazolone
of the ester group of 12 with hydra-
[path hi. In conclusion,
compound
containing
the present work demonstrates a pyrazolo
ester 3 and hydrazine
method as shown is useful nucleosides.
ring is obtained
salt by a one-step
that a new type of tricyclic in good yield from enamino-
cyclization.
for the preparation
Also,
the synthetic
of fused pyrazolo
derivatives
of
7417
Chart
I
H EtOOC~ .
FI1
H Me---~ COOEr
NHR2 N
!
N
!
R
R
R
3 R2=H NH2 13 R2 = N(Me)2
1 R I = CI
R 5 R 3 = COOEt 10 R3 = CONH2
4
12 R 2 ~
2 R~= CH(CN)COOEt
R=
R ~
O
H N--N ~/
O O
~
N
N-3~,.N L ;,-
X
OR5
EIOOC4~5' N R7
I
R HO
Scheme
R
OH
COOEt
8
FI 4 =
11
R4 = CONH 2
6
R5 = H
7
R5 = Me
9
R6 =
H2, R7= H
1 4 R 6 = =CH-NH 2, R 7= Me
I
_._.. EIOOC~~N
E.oo
HNH2 N ..~~,,'-~ N
NH2NH2 3
I
R
R
12 I [bl
- NH3
~
6
5
,
References and Notes i) Present address: Department of Chemistry,
University of Virginia, McCormick
Road, Charlottesville, VA 22903, U.S.A. 2) Thomas, R. W.; Leonard, N. J., Heterocvcles, references cited therein;
1976, 5, 839, and
Chladek, S.; Abraham,
E., Nucleic Acids
7418
Res., 1976, 3, lic Compounds, Koomen, Go J., 3) Lin, P. K. T.; Bischofberger,
1215; Kost, A. A.; Ivanov, M. V., Chemistry of Heterocyc1980, 16, 209, and references cited therein; Odijk, W. M.; Tetrahedron, 1985, 41, 1893. Brown, D. M., Nucl_____eicAcids Res., 1989, 17, 10373; N.; Matteucci, M. D., J. Am, Chem. Soc., 1989, iii,
3041. 4) Patil, V. D.; Wise, D. S.; Wetting, L. L.; Bloomer, L. C.; Townsend, L. B., J. Med. Chem., 1985, 28, 423. 5) The compound was prepared in good yield by reaction of 3,4-dihydrotetrahydropyran with 6-chloro-9-(2,3-O-isopropylidene-~-D-ribofuranosyl)purine (Huisgen, A.; Maguire, M. H., J. Am. Chem. So_~c., 1961, 83, 150.) in the presence of p-toluenesulfonic acid. 6) Katritzky, A. R.; Ostercamp, D. L.; Yousaf, T. I., Tetrahedron, 1987, 43, 517. 7) The quantum yield (~F) was obtained from that of standard quinine sulfate in 0.025 M phosphate buffer, 21°C. (Secrist III, J. A.; Barrio, J. R.; Leonard, N. J.; Weber, G., Biochemistry, 1972, Ii, 3499). 8) Sundberg, R. J.; Ellis, J. E., J. Heterocl,cl. Chem., 1982, 19, 573. 9) 13C-NMR (DMSO-d6) for the aglycon moiety of 8:~ 14.3 (Me), 59.7 (CH2) , 103.6 (2j = 9.1 Hz, C-9), 123.8 (3j = 12.8 Hz, C-gb), 137.4 (3j = 4.4 Hz, C-9a), 138.7 (Ij = 216.7 Hz, C-5), 139.6 (m, C-3a), 140.7 (Ij = 214.8 Hz, 37 = 4.4 Hz, C-2), 146.8 (ij = 89.8 Hz, C-8), 161.7 (3j = 4 Hz, CO). i0) Anderson, P. L.; Hasak, J, P.; Kshle, A. D,; Paolella, N. A.; Shspiro, M. J., ~. Heterocycl. Chem., 1981, 18, 1149. ii) Yip, K. F.; Tsou, K. C., J. Or S . Chem., 1975, 40, 1066; Furukawa, Y.; Miyashita, O.; Honjo, M., Chem. Pharm. Bull., 1974, 22, 2552; Huang, G. F.; Maeda, M.; Kawazoe, Y., Tetrahedro_nn, 1975, 31, 1367. 12) Hosmane, R. S.; Lim, B. B., Synthesis, 1988, 242, snd references cited therein. 13) IH-NMR (CD3COCD 3) for the aglycon moiety of !4:~ 1o19 (t, 3H, Me), 3.74 (s, 3H, NMe), 4.11 (q, 2H, CH2) , 6.10 (m, 2H, NH2), 7.47 (t, ~ = 8.6 Hz, IH, C=CH), 7,65, 7.68 (2s, IH, H-2), 7.79 (s, IH, H-8). The position of N-methyl group on the pyrazole was determined by NOE (8%) with the methine proton. 13C-NMR(CDC]3) of the aglycon part of 14:~ 14,5 (Me), 37.6 (N-Me), 59.8 (CH2), 112.8 (3j = 10.2 Hz, C-4), 113.0 (2j = 8.8 Hz, C-4 ), 131.3, 131.7 (3j = 209.8 Hz, 3.2 ? 3 Hz, C-2), 139 1 (C]5), 139.5 (C-3), 140.2, 140.8 (i~ = 189.3 Hz, C-5 ), 152.1, 152.2 (Ij = 174.6 Hz, N=C), 162.5 (CO).
(Received in Japan 5 August 1991)
SYNTHESIS
AND MECHANISM
0040-4039/91 $3.00 + .00 Pergamon Press plc
OF FORMATION
OF NOVEL TRICYCLIC
3-~-D-RIBOFURANOSYLPYRAZOLO[3,2-!]PURINE ONE-STEP REACTION OF 6-ENAMINOPURINE
Norimitsu School
1-5-8,
DERIVATIVES, BY A WITH HYDRAZINE
Hamamichi I
of Pharmaceutical
Hatanodai
NUCLEOSIDES,
Sciences,
Shinagawa-ku,
Showa University,
Tokyo
142, Japan
Summary: Ethyl 3-~-D-ribofuranosylpyrazolo[3,2-!]purine-9-carboxylate (8) has been prepared from a fully protected 6-chloropurine derivative in four steps including a one-step reaction for the preparation of 3-~-D-ribofuranosyl[3,2-i]purine derivative 5 by 6-enaminopurine and hydrazine, and the mechanism of formation of 5 is discussed.
Polycyclic and pyrimidines binding pounds
nucleosides
with five- or six-membered
are an important
class
sites, 2 base-pair mismatches are known to exhibit
of compounds
a new kind of antitumor
In this paper the synthesis
and mechanism
derivatives,
from enamino-ester
by a one-step
Reaction
novel
and biological of novel
of formation tricyclic
reaction
of enzyme-
these comtricyclic
of 3-~-D-
nucleosides,
are described.
of 6-chloro-9-[2,3-O-isopropylidene-5-O-(2-tetrahydropyranyl)-
~-D-ribofuranosyl]purine DMF at room temperature
(1) 5 with ethyl gave 2 [solid;
cyanoacetate
IR (KBr):
(CO) cm-l; UV ~ max MeOH (g): 339 (34000), (Chart
activity
the synthesis
ribofuranosylpyrazolo[3,2-!]purine 3 and hydrazine
for the studies
of oligonucleotides. 3 Also,
activity.4 Much attention has been paid toward nucleosides.
rings fused to purines
I). Catalytic
hydrogenation
v/v) under medium pressure
3100
using sodium hydride (NH),
328 (sh, 29500)
2200 nm]
(CN),
in 85% yield
of 2 with 5% Pd-C in benzene-DMF
(I : i,
(4 atm) gave ethyl @-(aminomethylene)-9-[2,3-O-iso-
propylidene-5-(2-tetrahydropyranyl)-~-D-ribofuranosyl]purine-6-acetate [solid;
IR (KBr):
(11300), (KBr):
3400
263 (i1500),
2930,
28% yield.
(NH),
pyridine-ethanol
(~):
268 (6100),
nm]
UVNmax
1670 (CO) cm-l;
in 71% yield, MeOH
of 3 with hydrazine
(k):
UV X m a x MeOH
246 (7100),
sulfate
(~):
derivative 319 (sh,
ed with diazomethane
230 (19000),
66 [solid;
262 (8700) nm]
or hydrochloride
11900),
287 (15000)
FeCI 3 test:
341 (17800)
to give 7 [solid;
UV~max
7415
nm]
(3) (6):
236
together with 4 [solid;
(i : i, v/v) at 100°C for 3 h gave 5 [foam;
(CO) cm-l; U V x max MeOH with pyrazolone
3310 (NH),
320 (17000)
1735 (CO) cm-l;
Reaction
in
1655
nm]
in
(3 equiv.)
IR (KBr):
IR in
1700
in 86% yield along
green color;
UV ~ max MeOH
in 8% yield,
which was treat-
MeOH (~):
230 (sh, 7100),
300
7416
(17600),
310 (sh, 15700) nm]. Alternatively,
anol under reflux the products respectively.
Removal
with hydrazine
5 and 6 were obtained
of the protecting
groups
monohydrate
in 40% and 43% yields,
of 5 with trifluoroacetic
gave ethyl
3-~-D-ribofuranosylpyrazolo[3,2-!Jpurine-9-carboxylate
182-184°C;
fluorescence
kmax
emission:
233 nm; ~F=0"407 ] in 84%o yield. matic region appeared
at~ 8.57
tricyclic
ring appeared structure
that tricyclic derivative treatment
ring-opening
dec.;
upon ~Ikali
a pyrazolo
UV~max
MeOH
and hydrolysis
(~):
five-membered
the protecting
to give the amide fluorescence reaction
MeOH
groups
and 146.8
of 3 with hydrazine,
fluorescence
compound
the hydrszino
of 3 with dimethyl MS m/z:
532 (M+),
hydrazine
518 (M+),
(Scheme
derivative zine
it seems
6 is obtained
that first an addition
of
indicates
C-6 and N-I.
elimination
of
12, whose hydrazino
C-6 and N-I is cleaved
by cyclization
deriv-
The structure
spectroscopy. 13 This result
to 5 with elimination
which
the imidazole
to give the spiro intermediate
the linkage between which cyelizes
at 100°C
of 3 with methylhydra-
group of 3 takes place to give
at the C-6 carbon
I). Then,
Reaction
moiety of the purine ring is cleaved between
On the basis of these results
FABMS m/z:
for 2.5 h gave
in 80% yield,
262 (B + I)] was obtained.
by IH-NMR and 13C-NMR
acid
After brief
in ethanol
276 (B + i)]
to 5 by heating
zole derivative,
in ethanol.
gave
in 87%
that 12 is an intermediate
at 50°C for 20 h did not give 5, instead
to the enamine
of NMR to be
392 nm;
12 [solid;
of 12 in ethanol
zine 12 in ethanol
attacks
nm]
as follows.
was not converted
hydrazine
the
of 5 with ammonia
~ max emission:
This indicates
gave the adduct
MS m/z:
9
Also,
in 80% yield.
derivative
Heating
for both 5 and 6. Reaction
moiety
The
product
5 appears
287 (14800)
of 5 was elucidated
in 30% yield.
13 [solid;
in 58% yield.
Reaction
232 (21700),
236 nm; ~F=0.40J
5 in 53% yield and 6 in 25% yield.
that the pyrimidine
(C-8).
of which were removed using trifluoroacetic
of formation
14 was established
(s, IH,
to give 5, On the basis
ring,
nucleoside.
(~):
Ii [mp 206-208°C,
505 (MH+)] was isolated
ative 14 [solid;
and 9.57
ring I0 fused to
gave the ring-opened
orthoformate
tricyclic
k max excitation:
The mechanism
(C-9a)
293 (6900) nm]
of the pyrimidine
the amide i0 [foam; U V ~ m a x yield,
of pyrazole
treatment II and, as expected,
sodium hydroxide
ester 9 was cyclized with triethyl spectroscopy
137.4
by
of 8 in the aro-
confirmed by a chemical method. It is known such as N 6 -ethenoadenosine and pyrimido[2,l-i]purine
of 5 with aqueous
[mp 132-134°C
(DMSO-d6)
was further
compounds
undergo
(C-9),
acid
[mp
N max excitation:
8.71 (s, IH, H-2)
of 89, the carbons
at~ 103.6
(8)
of 5 and 8 were established
The IH~NMR signals (s, IH, H-5),
H-8) 8. In the 13C-NMR spectrum pyrimidine
384 nm; fluorescence
The structures
IH-NMR and 13C-NMR spectroscopy.
in eth-
[path a]
to give the pyra-
of ammonia.
Pyrazolone
of the ester group of 12 with hydra-
[path hi. In conclusion,
compound
containing
the present work demonstrates a pyrazolo
ester 3 and hydrazine
method as shown is useful nucleosides.
ring is obtained
salt by a one-step
that a new type of tricyclic in good yield from enamino-
cyclization.
for the preparation
Also,
the synthetic
of fused pyrazolo
derivatives
of
7417
Chart
I
H EtOOC~ .
FI1
H Me---~ COOEr
NHR2 N
!
N
!
R
R
R
3 R2=H NH2 13 R2 = N(Me)2
1 R I = CI
R 5 R 3 = COOEt 10 R3 = CONH2
4
12 R 2 ~
2 R~= CH(CN)COOEt
R=
R ~
O
H N--N ~/
O O
~
N
N-3~,.N L ;,-
X
OR5
EIOOC4~5' N R7
I
R HO
Scheme
R
OH
COOEt
8
FI 4 =
11
R4 = CONH 2
6
R5 = H
7
R5 = Me
9
R6 =
H2, R7= H
1 4 R 6 = =CH-NH 2, R 7= Me
I
_._.. EIOOC~~N
E.oo
HNH2 N ..~~,,'-~ N
NH2NH2 3
I
R
R
12 I [bl
- NH3
~
6
5
,
References and Notes i) Present address: Department of Chemistry,
University of Virginia, McCormick
Road, Charlottesville, VA 22903, U.S.A. 2) Thomas, R. W.; Leonard, N. J., Heterocvcles, references cited therein;
1976, 5, 839, and
Chladek, S.; Abraham,
E., Nucleic Acids
7418
Res., 1976, 3, lic Compounds, Koomen, Go J., 3) Lin, P. K. T.; Bischofberger,
1215; Kost, A. A.; Ivanov, M. V., Chemistry of Heterocyc1980, 16, 209, and references cited therein; Odijk, W. M.; Tetrahedron, 1985, 41, 1893. Brown, D. M., Nucl_____eicAcids Res., 1989, 17, 10373; N.; Matteucci, M. D., J. Am, Chem. Soc., 1989, iii,
3041. 4) Patil, V. D.; Wise, D. S.; Wetting, L. L.; Bloomer, L. C.; Townsend, L. B., J. Med. Chem., 1985, 28, 423. 5) The compound was prepared in good yield by reaction of 3,4-dihydrotetrahydropyran with 6-chloro-9-(2,3-O-isopropylidene-~-D-ribofuranosyl)purine (Huisgen, A.; Maguire, M. H., J. Am. Chem. So_~c., 1961, 83, 150.) in the presence of p-toluenesulfonic acid. 6) Katritzky, A. R.; Ostercamp, D. L.; Yousaf, T. I., Tetrahedron, 1987, 43, 517. 7) The quantum yield (~F) was obtained from that of standard quinine sulfate in 0.025 M phosphate buffer, 21°C. (Secrist III, J. A.; Barrio, J. R.; Leonard, N. J.; Weber, G., Biochemistry, 1972, Ii, 3499). 8) Sundberg, R. J.; Ellis, J. E., J. Heterocl,cl. Chem., 1982, 19, 573. 9) 13C-NMR (DMSO-d6) for the aglycon moiety of 8:~ 14.3 (Me), 59.7 (CH2) , 103.6 (2j = 9.1 Hz, C-9), 123.8 (3j = 12.8 Hz, C-gb), 137.4 (3j = 4.4 Hz, C-9a), 138.7 (Ij = 216.7 Hz, C-5), 139.6 (m, C-3a), 140.7 (Ij = 214.8 Hz, 37 = 4.4 Hz, C-2), 146.8 (ij = 89.8 Hz, C-8), 161.7 (3j = 4 Hz, CO). i0) Anderson, P. L.; Hasak, J, P.; Kshle, A. D,; Paolella, N. A.; Shspiro, M. J., ~. Heterocycl. Chem., 1981, 18, 1149. ii) Yip, K. F.; Tsou, K. C., J. Or S . Chem., 1975, 40, 1066; Furukawa, Y.; Miyashita, O.; Honjo, M., Chem. Pharm. Bull., 1974, 22, 2552; Huang, G. F.; Maeda, M.; Kawazoe, Y., Tetrahedro_nn, 1975, 31, 1367. 12) Hosmane, R. S.; Lim, B. B., Synthesis, 1988, 242, snd references cited therein. 13) IH-NMR (CD3COCD 3) for the aglycon moiety of !4:~ 1o19 (t, 3H, Me), 3.74 (s, 3H, NMe), 4.11 (q, 2H, CH2) , 6.10 (m, 2H, NH2), 7.47 (t, ~ = 8.6 Hz, IH, C=CH), 7,65, 7.68 (2s, IH, H-2), 7.79 (s, IH, H-8). The position of N-methyl group on the pyrazole was determined by NOE (8%) with the methine proton. 13C-NMR(CDC]3) of the aglycon part of 14:~ 14,5 (Me), 37.6 (N-Me), 59.8 (CH2), 112.8 (3j = 10.2 Hz, C-4), 113.0 (2j = 8.8 Hz, C-4 ), 131.3, 131.7 (3j = 209.8 Hz, 3.2 ? 3 Hz, C-2), 139 1 (C]5), 139.5 (C-3), 140.2, 140.8 (i~ = 189.3 Hz, C-5 ), 152.1, 152.2 (Ij = 174.6 Hz, N=C), 162.5 (CO).
(Received in Japan 5 August 1991)