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13C-NMR spectrum and absolute stereochemistry of furoscalarol
oo4o-403g/78/o6o1-204o#o2.oo/o
Tetrahedron Letters Ho. 23, PP 2041 - 2044, 1978. Printed in Great Britain. @ Perganwn Press Ltd.
13
C-NMR
SPECTRUM
AND ABSOLUTE
STEREOCHEMISTRY
OF FUROSCALAROL+
G. Cimino Laboratorio Napoli,
14 1-B. de1 C.N.R.-Via
per la Chimica
Toiano,
2, 80072 Arco
Felice,
Italy and F. Cafieri,
Istituto
di Chimica
cannone,
16 - I - 80134,
L. De Napoli e Biologica
Organica
Napoli,
and E. Fattorusso dell'bniversita
di Napoli,
Italy.
(Received in UK 4 March 1978; aocepted for Publication 13 April
In 1972, an uncommon ted from the marine of a number synthesis
could
cyclization
sponge
furoscalaro14
compound
is closely
genetically
from being
We wish
assignments
previously5 Three cetyl
types
the 13C chemical the detection decoupled
similar
triterpene-type
recently
compounds,
bio-
a further
and could
.for scalarin,
Cz5
This
derive
bio-
the only
spectrum.
of the stereochemistry Table
I contains
(2), its deacetyl
of this compo-
13C-NMR
derivative
data and re-
(3) and those
for scalarin. spectra
proton
were
resonance
values,
of non protonated
spectra
in Porifera Their
from the sponge C. mollior.
to that proposed
the determination
for furoscalarol
shift
reported'.
isola-
of the ring D.
of its 13C-NMR
(2): -
More
(I), was
the presence
was
by a standard
to the scalarin-like
a cyclization the closure
Latter,
group3.
isolated
1978)
scalarin'
the same skeleton
(_?), has been
of 13C-NMR
derivative
scalaris.
having
from geranylfarnesol
related
determined
sesterterpene,
at the isopropylidene
now to report
und on the basis lative
Cacospongia
take place
initiated
terpene,
difference
tetracarbocyclic
of sesterterpenes
Via Mezzo-
noise
run for furoscalarol decoupled
off-resonance
carbon
sites,
spectra
(I) and for its dea-
for the determination
decoupled
spectra
and single-frequency
(sford) 7 for the differentiation
of carbon
+ This work has been carried out in the frame of the l'oceanografia e i Fondi Marini", C.N.R., Roma. 2041
for
off-resonance
species.
"Progetto
(nord)6
of
Further
Finalizzato
per
as-
2042
No.
1
2
R = -0Ac
2
R=-OH
23
sistance was obtained by comparison with published data for structurally related compounds, especially diterpenes* and scalarin-like sesterterpenes51g of known stereochemistry. The assignment
of the signals of the furan carbons was based on
published datalo. Comparison of the *C-NMR spectra of 2 and 211 with that of 1 allowed ready recognition of the signals corresponding to the carbon atoms of the rings A and B. Similarly, the four methyl groups on these two rings were identified. Assignments for C-23 and C-24 were tentative and were based on the fact that the chemical shift value of C-23 in 1 should be very similar to that assigned to C-23 of scalarin12. The signals corresponding to the functionalized C-12 and to the two adjacent carbons were readily recognized by comparison of 13C-NMR spectrum of -2 with that of its deacetyl derivative
(3). In the spectrum of 2 the signal due to C-12
showed an expected upfield shift13, while the signals due to C-II and C-13 shifted downfield as a consequence of deacetylation13. The two off-resonance doublets at 6 49.8 and 6 66.5 in the spectrum of 2 were ascribed to C-14 and C-16, respectively. This cherlical shift difference can be well explained on the basis that the hydroxysubstituted carbon atom (C-16) must be more deshielded. The resonance due to C-9 and C-14 were in agreement with the axial orientation of the acetoxy substituent at C-125'* and the quasi-equatorial orientation of the hydroxy substituent at C-165'8, both assigned on the basis of the 'H-NMR of 2 (CgDg; H12 at 6 5.40, W l/2 ~a. 6 Hz; H16 at 6 4.64, dd, J 9 and 5 Hz). The remaining two signals at 6 29.3 and 6 22.1 were ascribed to C-15 and C-25, respectively, on the basis of their multiplicity. The signal due to the C-25 angular methyl group, compared with that of scalarin(
No.
23
2043
showed an expected downfield shift. In fact, in 1 the C-25 methyl group is shielded by its y-gauche interaction with the C-19 methyne group. On the basis of the above spectral data, in agreement with the previous findings for scalarin-like sesterterpenes"',
a --trans.-anti-trans configuration must be suggested for the A/B
and B/C ring junctions of 2. The remaining C/D trans fusion has been assigned considering that the chemical shifts of C-14 and C-II require guasi-axial orientations for H-14 and Me-25, respectively. All these data led us to assign the relative stereochemistry of furoscalarol. The Horeau method14 applied to 2 allowed to determine the chirality at C-16 as 5, and this determines the absolute stereochemistry of 2. TABLE ========z===I Carbon-13 chemical shifts+ for compounds Is, 2 and 2
3
2.
C-l
c-2 c-3 c-4 c-5 C-6 C-7 C-8 c-9 C-IO C-II c-12 c-13 c-14 c-15 C-16 c-17 C-18 c-19 c-20 c-21 c-22 C-23 C-24 C-25 CH&O CH,CO -
39.8 18.1 41.6 33.3 56.5 18.5 42.1 37.9 52.5 37.4 22.4 74.6 36.9 49.9 24.2 135.3 128.1 50.8 98.9 167.8 33.3 21.4 16.1 16.1 15.1 171.0 21.4
(a) (b)
(a) (b) (d)
(d)
(c) (c)
39.6 18.1 41.3 33.2 56.5 18.5 41.9 36.9 53.0 37.1 21.7 73.5 40.7 49.8 25.3 66.5 120.0 156.6 140.9 108.1 33.2 21.3 15.9 17.2 22.1 170.0 21.0
(a) (b)
(a) (b) (c) (c)
(d)
(d)
38.4 17.3 40.5 32.1 55.4 17.7 41.0 36.0 50.7 36.4 23.9 69.6 42.0 47.4 29.0 65.4 121.1 157.2 139.6 108.3 32.1 20.2 15.2 16.4 21.6 --_
(a) (b)
(a) (b) (c) (c)
+Solutions in CDCla for 1 and 2 and C5D5N for 1; 25.20 MHz; Varian XL-100 Fourier Transform spectrometer; chemical shifts in p.p.m. from internal Me,Si. (a-d) Assignments may be reversed. ACKNOWLEDGEMENT We are indebted to Dr. Y. Kashman for a preprint of its paper and to Mr. C. Di Pinto for 13C-Nbm spectra.
x)44
Bo. 23
REFERENCES AND NOTES 1.
E. Fattorusso, S. Magno, C. Santacroce and D. Sica, Tetrahedron 28, 5993 (1972).
2.
G. Cimino, S. De Stefano and L. Minale, Experientia 2,
846 (1974).
G. Cimino, S. De Stefano and L. Minale, Experientia 2,
934 (1973).
G. Cimino, P. De Luca, S.De Stefano and L.Minale, Tetrahedron 21, 271 (1975). R. Kazlaulkas I P.I.Murphy, R.J. Quinn and R.J.Wells, Tetrahedron Letters, 2631 (1976). F. Cafieri, L .De Napoli, E. Fattorusso, C. Santacroce and D. Sica, Tetrahedron Letters, 477 (1977). F. CaFiJri, L . Cz Napoli, E. Fattorusso and C. Santacroce, Experientia 33, 994 (1977). 3.
G. A. Cordell, Phytochemistry 13, 2343 (1974).
4.
F. Cafieri, L. De Napoli, E. Fattorusso, C. Santacroce and D. Sica, --Gazz. Chim.it 107, 71 (1977). . 5. b. Cimino, S. De Stefano, L. Finale and H. Trivellone, 2. --Chen. Sot. Perkin I, 1587 (1977 . 6.
J. Amer. Chem. Sot. 91, E. Wenkert A. 0. Clouse, D. W. Cochran and D. Doddrell, ---6879 (19691
7.
G. C. Levy anf G. L. Nelson, "Carbon-13 Nuclear Magnetic Resonance for Organic Chemists", Wiley - Interscience, New York, 1972.
a.
I. Wahlbery, S. Almqvist, T. Nishida and C. R. Enzell, -Acta Chem. Stand. g 2, 1047 (1975).
9.
Y. Kashman and A. Rudi, Tetrahedron 33, 2997 (1977).
‘I
10.
A. Kiewict, J. De Wit, W. D. Weringa, Org. Msg. Reson. 5, 461 (1974).
11.
It is to be noted that the 13C-NMR spectrum has been run in CgDgN, which causes an upfield shift of all sp3 carbon signals.
12.
Our assignments agree with those recently published by Kashman and Rudig for heteronemin, except for the chemical shifts of C-l (41.7 p.p.m.) and C-O or C-IO (39.9 p.p.m.). In our opinion, besides all arguments reported throughout the text, the close similarity of the CMR spectra for a series of several scalarin-like compounds5 supportes our assignments.
13.
H. J. Reich, M. Jautelat, M. I. Messe, F. J. Weigert and J. D. Roberts, 2. Amer. Chem. Sot. 91, 7495 (1969). -14. A. Horeau, Tetrahedron Letters,506 (1961); ibid.,965 (1962).
Tetrahedron Letters Ho. 23, PP 2041 - 2044, 1978. Printed in Great Britain. @ Perganwn Press Ltd.
13
C-NMR
SPECTRUM
AND ABSOLUTE
STEREOCHEMISTRY
OF FUROSCALAROL+
G. Cimino Laboratorio Napoli,
14 1-B. de1 C.N.R.-Via
per la Chimica
Toiano,
2, 80072 Arco
Felice,
Italy and F. Cafieri,
Istituto
di Chimica
cannone,
16 - I - 80134,
L. De Napoli e Biologica
Organica
Napoli,
and E. Fattorusso dell'bniversita
di Napoli,
Italy.
(Received in UK 4 March 1978; aocepted for Publication 13 April
In 1972, an uncommon ted from the marine of a number synthesis
could
cyclization
sponge
furoscalaro14
compound
is closely
genetically
from being
We wish
assignments
previously5 Three cetyl
types
the 13C chemical the detection decoupled
similar
triterpene-type
recently
compounds,
bio-
a further
and could
.for scalarin,
Cz5
This
derive
bio-
the only
spectrum.
of the stereochemistry Table
I contains
(2), its deacetyl
of this compo-
13C-NMR
derivative
data and re-
(3) and those
for scalarin. spectra
proton
were
resonance
values,
of non protonated
spectra
in Porifera Their
from the sponge C. mollior.
to that proposed
the determination
for furoscalarol
shift
reported'.
isola-
of the ring D.
of its 13C-NMR
(2): -
More
(I), was
the presence
was
by a standard
to the scalarin-like
a cyclization the closure
Latter,
group3.
isolated
1978)
scalarin'
the same skeleton
(_?), has been
of 13C-NMR
derivative
scalaris.
having
from geranylfarnesol
related
determined
sesterterpene,
at the isopropylidene
now to report
und on the basis lative
Cacospongia
take place
initiated
terpene,
difference
tetracarbocyclic
of sesterterpenes
Via Mezzo-
noise
run for furoscalarol decoupled
off-resonance
carbon
sites,
spectra
(I) and for its dea-
for the determination
decoupled
spectra
and single-frequency
(sford) 7 for the differentiation
of carbon
+ This work has been carried out in the frame of the l'oceanografia e i Fondi Marini", C.N.R., Roma. 2041
for
off-resonance
species.
"Progetto
(nord)6
of
Further
Finalizzato
per
as-
2042
No.
1
2
R = -0Ac
2
R=-OH
23
sistance was obtained by comparison with published data for structurally related compounds, especially diterpenes* and scalarin-like sesterterpenes51g of known stereochemistry. The assignment
of the signals of the furan carbons was based on
published datalo. Comparison of the *C-NMR spectra of 2 and 211 with that of 1 allowed ready recognition of the signals corresponding to the carbon atoms of the rings A and B. Similarly, the four methyl groups on these two rings were identified. Assignments for C-23 and C-24 were tentative and were based on the fact that the chemical shift value of C-23 in 1 should be very similar to that assigned to C-23 of scalarin12. The signals corresponding to the functionalized C-12 and to the two adjacent carbons were readily recognized by comparison of 13C-NMR spectrum of -2 with that of its deacetyl derivative
(3). In the spectrum of 2 the signal due to C-12
showed an expected upfield shift13, while the signals due to C-II and C-13 shifted downfield as a consequence of deacetylation13. The two off-resonance doublets at 6 49.8 and 6 66.5 in the spectrum of 2 were ascribed to C-14 and C-16, respectively. This cherlical shift difference can be well explained on the basis that the hydroxysubstituted carbon atom (C-16) must be more deshielded. The resonance due to C-9 and C-14 were in agreement with the axial orientation of the acetoxy substituent at C-125'* and the quasi-equatorial orientation of the hydroxy substituent at C-165'8, both assigned on the basis of the 'H-NMR of 2 (CgDg; H12 at 6 5.40, W l/2 ~a. 6 Hz; H16 at 6 4.64, dd, J 9 and 5 Hz). The remaining two signals at 6 29.3 and 6 22.1 were ascribed to C-15 and C-25, respectively, on the basis of their multiplicity. The signal due to the C-25 angular methyl group, compared with that of scalarin(
No.
23
2043
showed an expected downfield shift. In fact, in 1 the C-25 methyl group is shielded by its y-gauche interaction with the C-19 methyne group. On the basis of the above spectral data, in agreement with the previous findings for scalarin-like sesterterpenes"',
a --trans.-anti-trans configuration must be suggested for the A/B
and B/C ring junctions of 2. The remaining C/D trans fusion has been assigned considering that the chemical shifts of C-14 and C-II require guasi-axial orientations for H-14 and Me-25, respectively. All these data led us to assign the relative stereochemistry of furoscalarol. The Horeau method14 applied to 2 allowed to determine the chirality at C-16 as 5, and this determines the absolute stereochemistry of 2. TABLE ========z===I Carbon-13 chemical shifts+ for compounds Is, 2 and 2
3
2.
C-l
c-2 c-3 c-4 c-5 C-6 C-7 C-8 c-9 C-IO C-II c-12 c-13 c-14 c-15 C-16 c-17 C-18 c-19 c-20 c-21 c-22 C-23 C-24 C-25 CH&O CH,CO -
39.8 18.1 41.6 33.3 56.5 18.5 42.1 37.9 52.5 37.4 22.4 74.6 36.9 49.9 24.2 135.3 128.1 50.8 98.9 167.8 33.3 21.4 16.1 16.1 15.1 171.0 21.4
(a) (b)
(a) (b) (d)
(d)
(c) (c)
39.6 18.1 41.3 33.2 56.5 18.5 41.9 36.9 53.0 37.1 21.7 73.5 40.7 49.8 25.3 66.5 120.0 156.6 140.9 108.1 33.2 21.3 15.9 17.2 22.1 170.0 21.0
(a) (b)
(a) (b) (c) (c)
(d)
(d)
38.4 17.3 40.5 32.1 55.4 17.7 41.0 36.0 50.7 36.4 23.9 69.6 42.0 47.4 29.0 65.4 121.1 157.2 139.6 108.3 32.1 20.2 15.2 16.4 21.6 --_
(a) (b)
(a) (b) (c) (c)
+Solutions in CDCla for 1 and 2 and C5D5N for 1; 25.20 MHz; Varian XL-100 Fourier Transform spectrometer; chemical shifts in p.p.m. from internal Me,Si. (a-d) Assignments may be reversed. ACKNOWLEDGEMENT We are indebted to Dr. Y. Kashman for a preprint of its paper and to Mr. C. Di Pinto for 13C-Nbm spectra.
x)44
Bo. 23
REFERENCES AND NOTES 1.
E. Fattorusso, S. Magno, C. Santacroce and D. Sica, Tetrahedron 28, 5993 (1972).
2.
G. Cimino, S. De Stefano and L. Minale, Experientia 2,
846 (1974).
G. Cimino, S. De Stefano and L. Minale, Experientia 2,
934 (1973).
G. Cimino, P. De Luca, S.De Stefano and L.Minale, Tetrahedron 21, 271 (1975). R. Kazlaulkas I P.I.Murphy, R.J. Quinn and R.J.Wells, Tetrahedron Letters, 2631 (1976). F. Cafieri, L .De Napoli, E. Fattorusso, C. Santacroce and D. Sica, Tetrahedron Letters, 477 (1977). F. CaFiJri, L . Cz Napoli, E. Fattorusso and C. Santacroce, Experientia 33, 994 (1977). 3.
G. A. Cordell, Phytochemistry 13, 2343 (1974).
4.
F. Cafieri, L. De Napoli, E. Fattorusso, C. Santacroce and D. Sica, --Gazz. Chim.it 107, 71 (1977). . 5. b. Cimino, S. De Stefano, L. Finale and H. Trivellone, 2. --Chen. Sot. Perkin I, 1587 (1977 . 6.
J. Amer. Chem. Sot. 91, E. Wenkert A. 0. Clouse, D. W. Cochran and D. Doddrell, ---6879 (19691
7.
G. C. Levy anf G. L. Nelson, "Carbon-13 Nuclear Magnetic Resonance for Organic Chemists", Wiley - Interscience, New York, 1972.
a.
I. Wahlbery, S. Almqvist, T. Nishida and C. R. Enzell, -Acta Chem. Stand. g 2, 1047 (1975).
9.
Y. Kashman and A. Rudi, Tetrahedron 33, 2997 (1977).
‘I
10.
A. Kiewict, J. De Wit, W. D. Weringa, Org. Msg. Reson. 5, 461 (1974).
11.
It is to be noted that the 13C-NMR spectrum has been run in CgDgN, which causes an upfield shift of all sp3 carbon signals.
12.
Our assignments agree with those recently published by Kashman and Rudig for heteronemin, except for the chemical shifts of C-l (41.7 p.p.m.) and C-O or C-IO (39.9 p.p.m.). In our opinion, besides all arguments reported throughout the text, the close similarity of the CMR spectra for a series of several scalarin-like compounds5 supportes our assignments.
13.
H. J. Reich, M. Jautelat, M. I. Messe, F. J. Weigert and J. D. Roberts, 2. Amer. Chem. Sot. 91, 7495 (1969). -14. A. Horeau, Tetrahedron Letters,506 (1961); ibid.,965 (1962).