4232
M. Nishizawa et al. / Tetrahedron Letters 48 (2007) 4229–4233
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OH
N
COOMe
N
2123–2126.
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COONa
N
OH
OH
COOMe
COOMe
COONa
COONa
O
O
H
H
H
H
32
33
34
Scheme 4.
Table 1. Morphogenesis-inducing activity against M. oxyspermum
after 7 days cultivation
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Compound
MEC (fmol/mL)a
Natural Thallusin (3)
Synthetic ( )-Thallusin (23)
Natural product derivative 32
Natural product derivative 33
31
3.8
7.6
3900
15,600
1630
Inactive
34
a MEC was measured as the mean of the three independent tests.
shown in Table 1, natural thallusin (3) showed activity
even at 3.8 fmol/mL,1 and synthetic ( )-thallusin also
showed comparable activity (at 7.6 fmol/mL). Interest-
ingly, thallusin analog ( )-31 showed substantial activ-
ity (at 1630 fmol/mL) that was more potent than that
of trimethyl ester 32 or the reduction product 33. Model
compound 34 did not show any morphogenesis-inducing
activity or growth inhibitory activity. These results sug-
gest that the free carboxylic residues and picolinic acid
moiety are indispensable for morphogenesis-inducing
activity and that the diterpene skeleton also plays an
important role.
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15208.
Thus, we completed the total synthesis of ( )-thallusin
based on the Hg(OTf)2–TMU complex induced biomi-
metic olefin cyclization and Suzuki coupling with pyr-
idylboronic acid derivative as the key steps, and we
developed a novel Hg(OTf)2-catalyzed olefin isomeriza-
tion leading to thermodynamically more stable isomer
by using in toluene.
Acknowledgment
10. Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33,
6299–6302.
This study was financially supported by a Grant-in-Aid
from the Ministry of Education, Culture, Sports, Sci-
ence, and Technology of the Japanese Government.
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Supplementary data
Supplementary data associated with this article can be
15. Crystal data for 27: A single crystal of 27 was obtained by
the recrystallization from hexane/dichloromethane. The
crystal was a colorless cube (dimensions 0.20 · 0.20 ·
0.20 mm) and was stable at room temperature. Measure-
ments were performed with a Mac Science (Bruker
Nonius) dip image plate diffractometer using graphite-
References and notes
˚
monochromated Mo Ka radiation (l = 0.71073 A). Cell
˚
parameters were as follows: a = 6.5980 (3) A, b = 23.6990
1. Matsuo, Y.; Imagawa, H.; Nishizawa, M.; Shizuri, Y.
˚
˚
(12) A, c = 13.8790 (8) A, b = 92.133 (2)ꢁ, V = 2168.7
Science 2005, 307, 1598.