Angewandte
Chemie
(1; [a]2D1 = + 50.08 (c = 0.21, EtOH)),[22] in 42% yield together
with 29 (4%), although an appreciable amount of uncon-
verted 28 (31%) was recovered. In this particular case,
Grubbsꢀ second-generation catalyst 31 turned out to be less
effective and gave 1 in less than 30% yield. The spectral data
of 1 thus obtained show good agreement with those repor-
ted[4b,c] for the natural specimen.
In addition, we investigated the ring-closing metathesis of
20, 22, 26, and 36 using catalysts 30 and 31 (Scheme 4). These
results revealed that the mode of metathesis largely depends
upon the structure of the substrate. Importantly, neither 32
nor 37 could be converted into 1 because of the extreme
instability arising from their tetrahydroindole structures
under basic conditions.
In conclusion, we have demosntrated the first total
synthesis of (+)-b-erythroidine, a non-aromatic Erythrina
alkaloid, in naturally occurring form by employing Lewis acid
promoted cyclization of the epoxy-trichloroacetimidate and
tandem ring-closing metathesis of the dienyne as key steps.
The present work opens a new avenue for the enantioselective
synthesis of Erythrina alkaloids.
Figure 1. Significant NOE observed in the NOESY NMR spectra of
aldol 23 and its C12 epimer.
troublesome because dehydration always took place predom-
inantly. Therefore, we next investigated the approach based
on an SmI2-mediated intramolecular Reformatsky reac-
tion.[21] In this case, acylation of 23 with bromoacetyl chloride
in the presence of pyridine took place successfully to give
bromoacetate 24 together with a small amount of the
corresponding dehydrated product, although 24 was chroma-
tographically unstable. Without purification, treatment of 24
with SmI2 in THF at room temperature led to cyclization to
give lactone 26 as a mixture of epimers (60:40). Treatment of
26 with thionyl chloride in pyridine caused dehydration to
give an inseparable mixture of a,b-unsaturated lactone 27 and
b,g-unsaturated lactone 28 (74:26). Gratifyingly, in this
particular case, saponification followed by acidification
allowed highly selective production of the b,g-lactone to
give a mixture of 27 and 28 in a ratio of 6:94. Finally,
treatment of this isomeric mixture with 0.1 equivalents of
Grubbsꢀ first-generation catalyst 30 in CH2Cl2 at room
temperature for 6.5 h cleanly furnished (+)-b-erythroidine
Received:January 18, 2006
Published online:March 21, 2006
Keywords: alkaloids · erythroidine · natural products ·
.
ring-closing metathesis · total synthesis
[1] For reviews, see:a) A. S. Chawla, V. K. Kapoor in Alkaloids:
Chemical and Biological Perspectives, Vol. 9 (Ed.:S. W. Pellet-
ier), Pergamon, Oxford, 1993, pp. 86 – 153; b) Y. Tsuda, T. Sano
in The Alkaloids, Vol. 48 (Ed.:G. A. Cordell), Academic Press,
New York, 1996, pp. 249 – 337.
[2] Members of the Erythrina family display curare-like and
hypnoptic activity as well as a variety of pharmacological effects,
such as sedative, hypotensive, neuromascular-blocking, and CNS
activity. See:A. Padwa, R. Henning, C. O. Kappe, T. S. Roger, J.
Org. Chem. 1998, 63, 1144 – 1155, and references therein.
[3] For recent reports on the construction of the erythrinane
skeleton, see:a) A. J. Blake, C. Gill, D. A. Greenhalgh, N. S.
Simpkins, F. Zhang, Synthesis 2005, 3287 – 3292; b) A. Padwa,
H. I. Lee, P. Rashatasakhon, M. Rose, J. Org. Chem. 2004, 69,
8209 – 8218; c) S. A. A. El Biary, H. Braun, L. F. Tietze, Angew.
Chem. 2004, 116, 5505 – 5507; Angew. Chem. Int. Ed. 2004, 43,
5391 – 5393; d) S. M. Allin, G. B. Streetley, M. Slater, S. L. James,
W. P. Martin, Tetrahedron Lett. 2004, 45, 5493 – 5496; e) Y. Yasui,
K. Suzuki, T. Matsumoto, Synlett 2004, 619 – 622; f) Y. Yasui, Y.
Koga, K. Suzuki, T. Matsumoto, Synlett 2004, 615 – 618; g) C.
Gill, D. A. Greenhalgh, N. S. Simpkins, Tetrahedron Lett. 2003,
44, 7803 – 7807; h) M. M. Abelman, J. F. Curtis, D. R. James,
Tetrahedron Lett. 2003, 44, 6527 – 6531; i) H. I. Lee, M. P.
Cassidy, P. Rashatasakhon, A. Padwa, Org. Lett. 2003, 5, 5067 –
5070; j) M. A. Guerrero, R. Cruz-Almanza, L. D. Miranda,
Tetrahedron 2003, 59, 4953 – 4958; k) H. Fukumoto, T. Esumi, J.
Ishihara, S. Hatakeyama, Tetrahedron Lett. 2003, 44, 8047 – 8049;
l) K. Shimizu, M. Takimoto, M. Mori, Org. Lett. 2003, 5, 2323 –
2325; m) S. Chikaoka, A. Toyao, M. Ogasawara, O. Tamura, H.
Ishibashi, J. Org. Chem. 2003, 68, 312 – 318; n) S. M. Allin, S. L.
James, M. R. J. Elsegood, W. P. Martin, J. Org. Chem. 2002, 67,
9464 – 9467; o) L. M. Miranda, S. Z. Zard, Org. Lett. 2002, 4,
1135 – 1138; p) T. Kawasaki, N. Onoda, H. Watanabe, T.
Kitahara, Tetrahedron lett. 2001, 42, 8003 – 8006; q) C. Jousse-
Scheme 4. Ring-closing metathesis of dienynes. The reactions were
carried out using Grubbs’ catalysts 30 or 31 (0.1 or 0.2 equiv) in
CH2Cl2 (0.05m).
Angew. Chem. Int. Ed. 2006, 45, 2731 –2734
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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