ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Total Synthesis of (()-Sorocenol B
Employing Nanoparticle Catalysis
Huan Cong and John A. Porco Jr.*
Department of Chemistry, Center for Chemical Methodology and Library Development
(CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, Massachusetts
02215, United States
Received March 28, 2012
ABSTRACT
The total synthesis of (()-sorocenol B has been accomplished featuring key steps including silver nanoparticle (AgNP)-catalyzed DielsꢀAlder
cycloaddition and late-stage Pd(II)-catalyzed oxidative cyclization. The synthetic natural product exhibited low micromolar cytotoxic activity
against a number of human cancer cell lines.
Nanoparticlecatalysishasemergedasa rapidlygrowing,
multidisciplinary research area leading to increasing appli-
cations in organic synthesis.1 The development of nano-
particle-mediated methodologies to access complex mole-
cules, especially natural products, is particularly attractive
but has been achieved with limited success thus far.2
Herein, we report the first synthesis of the natural product
sorocenol B in racemic form employing silver nanopar-
ticle (AgNP)-catalyzed DielsꢀAlder cycloadditions of
20-hydroxychalcones.3
Sorocenol B (1) was isolated from the root bark of
Sorocea bonplandii with an overall yield of 3 mg per
kilogram of dried bark.4 Due to the sparse distribution
of its natural plant source, there has been no further report
on this natural product since its first isolation in 1995.5
Structurally, compound 1 is characterized by an intriguing
bicyclo[3.3.1] core which is postulated to be biosynthetically
derived from oxidative cyclization of 20-hydroxychalcone-
derived DielsꢀAlder cycloadduct 2 (Scheme 1).4 Natural
products containing similar bicyclic core structures include
mulberrofuran I (3),6 australisin B (4),7 and mongolicin C
(5)8 which are structurally related to chalcomoracin (6)9
and mulberrofuran C (7),10 respectively.
In our retrosynthetic analysis (Scheme 2), (()-1 may be
derived from MOM acetal precursor 8 which may be
prepared through biomimetic, late-stage oxidative cycliza-
tion of cycloadducts 9 and/or 10. We envisioned that the
synthesis of 9/10 could be achieved employing AgNP-
catalyzed DielsꢀAlder cycloaddition3 between 20-hydro-
xychalcone 11 and diene 12 which should be derived from
commercially available chromene 13 and resorcinol 14,
respectively.
The synthesis of the acetylated chalcone 11 commenced
with ClaisenꢀSchmidt condensation between chromene
(1) (a) Nanoparticles and Catalysis; Astruc, D., Ed.; Wiley-VCH:
Weinheim, Germany, 2007. (b) Myers, V. S.; Weir, M. G.; Carino, E. V.;
Yancey, D. F.; Pande, S.; Crooks, R. M. Chem. Sci. 2011, 2, 1632. (c) Patil,
N. T. ChemCatChem 2011, 3, 1121.
(6) Hano, Y.; Fukai, T.; Nomura, T.; Uzawa, J.; Fukushima, K.
Chem. Pharm. Bull. 1984, 32, 1260.
(7) Zhang, Q. J.; Tang, Y. B.; Chen, R. Y.; Yu, D. Q. Chem.
Biodiversity 2007, 4, 1533.
(2) Cong, H.; Porco, J. A. ACS Catal. 2012, 2, 65.
(8) Kang, J.; Chen, R. Y.; Yu, D. Q. Planta Med. 2006, 72, 52.
(9) Takasugi, M.; Nagao, S.; Masamune, T.; Shirata, A.; Takahashi,
K. Chem. Lett. 1980, 9, 1573.
(10) (a) Hano, Y.; Suzuki, S.; Nomura, T.; Iitaka, Y. Heterocycles
1988, 27, 2315. For synthetic studies, see: (b) Gunawan, C.; Rizzacasa,
M. A. Org. Lett. 2010, 12, 1388. (c) Boonsri, S.; Gunawan, C.; Krenske,
E. H.; Rizzacasa, M. A. Org. Biomol. Chem. 2012DOI: 10.1039/
c2ob25115a.
(3) (a) Cong, H.; Becker, C. F.; Elliott, S. J.; Grinstaff, M. W.; Porco,
J. A. J. Am. Chem. Soc. 2010, 132, 7514. (b) For a recent application of
the AgNP catalyst to natural product synthesis, see: Chee, C. F.; Lee,
Y. K.; Buckle, M. J. C.; Rahman, N. A. Tetrahedron Lett. 2011, 52, 1797.
(4) Hano, Y.; Yamanaka, J.; Nomura, T.; Momose, Y. Heterocycles
1995, 41, 1035.
(5) Based on a Scifinder search as of March 26, 2012.
r
10.1021/ol300800r
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