1
250
K. Kumar Rana et al.
LETTER
trans. This can be rationalised from our earlier results6 References and Notes
and by invoking well-known conformational effects in the
(
1) (a)‘Chemistry of Lignans’, ed. C.B.S. Rao, Andhra University
Press 1978. (b) Whiting, D.A. Nat. Prod. Rep. 1985, 191;
1987, 499; 1990, 349. (c) Ward, R.S. Nat. Prod. Rep. 1993,
10, 1; 1995, 12, 183; 1997, 14, 43.
8
intermediates although the NOE experiment (no en-
hancement) on C -H and C -H remained inconclusive.
2
3
1
The ratio of the two isomers was determined from the H
NMR spectrum of the crude cyclised product. The C-2
benzylic proton appeared as doublet at 4.79 (J = 6.4 Hz)
for the major isomer and at 4.58 (J = 8.0 Hz) for the mi-
nor isomer in the crude product from 3a and doublet at
(2) Gottlieb, O.R. in ‘New Natural Products and Plant Drugs
with Pharmacological, Biological or therapeutical Activity’,
Springer-Verlag, Berlin-Heidelberg 1987, pp. 227-248.
(
3) (a) Lin-Zen, Z.; Seligmann, O.; Lotter, H.; Wagner, H.
Phytochemistry 1983, 22, 265. (b) Vidigal, M.C.S.;
Cavalheiro, A.J.; Kato, M.J.; Yoshida, M. Phytochemistry
4
.79 (J = 6.5 Hz) for the major isomer and at 4.60
(
J = 7.9 Hz) for the minor isomer in the crude product
1995, 40, 1259.
from 3b. The major isomers 4a and 4b were separated by
(4) (a) Stevens, D.R.; Whiting, D.A. J. Chem. Soc., Perkin Trans.
1 1990, 425; 1992, 633. (b) Mitra, J.; Mitra, A.K.. J. Chem.
Soc., Perkin Trans. 1 1992, 1285.
preparative TLC (20% ethyl acetate in petroleum ether) in
9
6
4% and 63% yields respectively. The spectral data of
(
5) RajanBabu, T.V.; Nugent, W.A. J. Am. Chem. Soc. 1994, 116,
86.
6) (a) Adhikari, S.; Roy, S. Tetrahedron Lett. 1992, 33, 6025.
the major isomer 4a was identical with those of
9
3
a,8
9
dihydrosesamin and the spectra data of 4b was identi-
(
3
b
cal with those of acuminatin methyl ether. The observed
stereochemistries of the major products were further sup-
ported by performing the NOESY experiment on 4a in
(
(
b) Roy, S.C.; Adhikari, S.; Tetrahedron 1993, 49, 8415.
c) Maiti, G.; Adhikari, S.; Roy, S.C. Tetrahedron Lett. 1994,
35, 3985. (d) Maiti, G.; Adhikari, S.; Roy, S.C. J. Chem. Soc.
Perkin Trans. 1 1995, 927. (e) Mandal, P.K.; Maiti, G.; Roy,
S.C. J. Org. Chem. 1998, 63, 2829.
CDCl . Since neither the minor isomer nor a derivative
3
formed by reaction of its hydroxy group could be separat-
ed chromatographically in pure form, its stereochemistry
remains uncertain. To our knowledge, this is the first re-
port of the synthesis of acuminatin methyl ether (4b). The
stereochemistry of the major product was finally con-
firmed by synthesising the bicyclic compound 5b from
(7) All new isolated compounds exhibited satisfactory analytical
and spectral data.
(
8) (a) Beckwith, A.L.J.; Easton, C.J.; Lawrence, T.; Serelis, A.K.
Aust. J. Chem. 1983, 36, 545. (b) Rajanbabu, T.V. Acc. Chem.
Res. 1991, 24, 139.
(9) Spectral data of 4a: H NMR (300 MHz) 1.61 (br s, OH),
1
2
.32-2.37 (m, 1H, C -H), 2.53 (dd, J = 13.2 and 10.3 Hz, 1H,
3
b. Thus, when 3b was treated with Cp TiCl in THF fol-
3
2
/
C -H), 2.63-2.76 (m, 1H, C -H), 2.87 (dd, J = 13.2 and 5.1
Hz, 1H, C -H), 3.69-3.78 (m, 2H, C -H), 3.89 (dd, J = 10.6
lowed by addition of iodine, a major compound 5b along
with a trace of another compound were furnished. The
major compound 5b was separated by preparative TLC in
4
4
/
/
4
3
and 6.9 Hz, 1H, C -H), 4.04 (dd, J = 8.4 and 6.4 Hz, 1H, C -
5
5
H), 4.79 (d, J = 6.4 Hz, 1H, C -H), 5.93 (s, 2H, OCH O), 5.94
2
2
1
0
8
8% yield and its spectral data were identical with a nat-
13
(
s, 2H, OCH O), 6.62-6.83 (m, 6H, Ar-H); C NMR (75
2
1
1
ural compound, kobusin, which is also named as methyl
MHz) 33.3, 42.3, 52.6, 60.9, 72.9, 82.9, 100.8, 100.9, 106.3,
1
2
13
piperitol or spinescin.
108.1, 108.3, 108.9, 119.0, 121.4, 134.2, 137.1, 145.9, 146.9,
1
1
47.8, 147.8. Spectral data of 4b: H NMR (300 MHz) 1.56
In conclusion, we have successfully achieved short and
stereoselective total synthesis of furano lignans contain-
ing both similar or different aromatic substituents, dihy-
drosesamin and acuminatin methyl ether in good overall
yield by radical cyclisation of epoxides using a transition-
metal radical source.
(
1
br s, OH), 2.33-2.42 (m, 1H, C -H), 2.56 (dd, J = 13.2 and
3
/
0.6 Hz, 1H, C -H), 2.68-2.78 (m, 1H, C -H), 2.92 (dd,
4
4
/
/
J = 13.2 and 5.0 Hz, 1H, C -H), 3.72-3.95 (m, 3H, 2C -H and
4
3
C -H), 3.86 (s, 3H, OCH ), 3.87 (s, 3H, OCH ), 4.05 (dd,
5
3
3
J = 8.5 and 6.5 Hz, 1H, C -H), 4.79 (d, J = 6.5 Hz, 1H, C -H),
5
2
1
3
5
.94 (s, 2H, OCH O), 6.68-6.88 (m, 6H, ArH); C NMR (75
2
MHz) 33.1, 42.3, 52.7, 55.9, 60.9, 72.9, 82.8, 100.9, 106.3,
108.0, 111.3, 111.9, 119.1, 120.4, 132.9, 137.0, 146.9, 147.5,
1
47.8, 149.0.
Acknowledgement
1
(
10) Spectral data of 5b: H NMR (300 MHz) 3.05-3.11 (m, 2H,
We gratefully acknowledge the financial support from Department
of Science and Technology, New Delhi. C.G. thanks CSIR, New
Delhi for the award of a Junior Research Fellowship.
C -H and C -H), 3.87-3.89 (m, 2H, C -H and C -H), 3.87 (s,
1
5
4
8
3H, OCH ), 3.89 (s, 3H, OCH ), 4.21-4.27 (m, 2H, C -H and
3
3
4
C -H), 4.73 (d, J = 3.7 Hz, 1H, benzylic proton), 4.74 (d,
8
J = 4.0 Hz, 1H, benzylic proton), 5.94 (s, 2H, OCH O), 6.76-
2
1
3
6
5
1
.90 (m, 6H, ArH); C NMR (75 MHz) 54.5, 54.7, 56.3,
6.4, 72.1, 72.2, 86.1, 86.2, 101.4, 106.9, 108.5, 109.7, 111.6,
18.6, 119.7, 134.0, 135.5, 147.5, 148.3, 149.1, 149.6.
(11) Iida, T.; Nakano, M.; Ito, K. Phytochemistry 1982, 21, 673.
(12) Pelter, A.; Ward, R.S. Tetrahedron 1976, 32, 2783.
(13) Brieskorn, C.H.; Huber, H. Tetrahedron Lett. 1976, 2221.
Article Identifier:
437-2096,E;2001,0,08,1249,1250,ftx,en;D09901ST.pdf
1
Synlett 2001, No. 8, 1249–1250 ISSN 0936-5214 © Thieme Stuttgart · New York