LETTER
Stereoselective Total Synthesis of Sporostatin
791
OMe
OMe
HOOC
O
b
c
a
HO
MeO
O
MeO
O
O
6
7
8
O
9
OH
O
OMe
O
e
d
HO
O
N
MeO
O
O
O
10
1
N
OMe
Cl
Ru
O
O
Cl
COOH
12
MeO
OH
HG
11
Scheme 2 Reagents and conditions: (a) CH2=CHMgBr, CuBr, THF, –78 °C to –40 °C, 6 h, 80%; (b) 11, DCC, DMAP, CH2Cl2, 3 h, r.t., 97%;
(c) 12, HG (5 mol%), CH2Cl2, 25 °C, 82%; (d) TFA, TFAA, reflux, 41%; (e) AlI3, Bu4N+I–, benzene, r.t., 95%.
trifluoroacetic anhydride at 60 °C for 30 minutes.3,8,9
(3) (a) Bringmann, G.; Lang, G.; Michel, M.; Heubes, M.
Tetrahedron Lett. 2004, 45, 2829. (b) Yoshino, T.; Ng, F.;
Deprotection of the methoxy groups of 10 using freshly
Danishefsky, S. J. J. Am. Chem. Soc. 2006, 128, 14185.
2,10
prepared AlI3 furnished the target molecule 1 in 94%
(c) Liang, Q.; Zhang, J.; Quan, W.; Sun, Y.; She, X.; Pan, X.
yield whose melting point and spectroscopic data were
J. Org. Chem. 2007, 72, 2694.
identical with the natural product.1b The specific rotation
(4) Bonini, C.; Chiummiento, L.; Lopardo, M. T.; Pullex, M.;
of synthetic sporostatin (1) is –18.8, which is exactly the
same value to that reported by Yaginuma et al.1b thereby
confirming the stereogenic center at C11 carbon as S.11
Colobert, F.; Solladie, G. Tetrahedron Lett. 2003, 44, 2695.
(5) Furrow, M. E.; Schaus, S. E.; Jacobsen, E. N. J. Org. Chem.
1998, 68, 6776.
(6) Kumar, P.; Gupta, P.; Naidu, V. Chem. Eur. J. 2006, 12,
In summary, we have described a simple and concise total
synthesis of sporostatin employing very simple and easily
accessible reactions such as Cu(I)-mediated ring opening
of chiral epoxide with vinyl magnesium bromide, esterifi-
cation, cross-metathesis reaction, and intramolecular
Friedel–Crafts reaction as key steps. The stereochemistry
at C11 in sporostatin (1) was determined as S.
1397.
(7) (a) BouzBouz, S.; Cossy, J. Tetrahedron Lett. 2006, 47,
901. (b) Garber, S.; Kingsbury, J. S.; Gray, B. L.; Hoveyda,
A. H. J. Am. Chem. Soc. 2002, 122, 8168. (c) Gessler, S.;
Randl, S.; Blechert, S. Tetrahedron Lett. 2004, 41, 9973.
(d) Wakematsu, H.; Blechert, S. Angew. Chem. Int. Ed.
2002, 41, 2403. (e) Kitamura, T.; Sato, Y.; Mori, M.
Tetrahedron 2004, 60, 9649. (f) Cossy, J.; Bargiggia, F.;
BouzBouz, S. Org. Lett. 2003, 459. (g) Kingsbury, J. S.;
Harrity, J. P. A.; Bonitatebus, P. J. Jr.; Hoveyda, A. H. J. Am.
Chem. Soc. 1999, 121, 791. (h) Hoffmann, T. J.; Rigby, J.
H.; Arseniyadis, S.; Cossy, J. J. Org. Chem. 2008, 73, 2400.
(8) Bracher, F.; Schulte, B. Liebigs Ann./Recl. 1997, 1979.
(9) (a) Kreipl, P. T.; Reid, C.; Steglich, W. Org. Lett. 2002, 4,
3287. (b) Konwar, D.; Boruah, R. C.; Sandhu, J. S.
Tetrahedron Lett. 1990, 31, 1063.
Acknowledgment
N.T. and K.U.G. thank CSIR, New Delhi for the award of fel-
lowships.
References and Notes
(10) (a) Reddy, M. V. R.; Yucel, A. J.; Ramachandran, P. V.
J. Org. Chem. 2001, 66, 2512. (b) Kumar, P.; Gupta, P.;
Naidu, S. V. Chem. Eur. J. 2006, 12, 1397. (c) Yadav, J. S.;
Niranjan Kumar, N.; Reddy, M. S.; Prasad, A. R.
Tetrahedron 2007, 12, 2689.
(1) (a) Murakami, Y.; Ishii, A.; Mizuno, S.; Yaginuma, S.;
Uehera, Y. Anticancer Res. 1999, 19, 4145. (b) Kinoshita,
K.; Sasaki, T.; Awata, M.; Takada, M.; Yaginuma, S.
J. Antibiot. 1997, 50, 961.
(2) (a) Edarada, R. A.; Heubes, M.; Brauers, G.; Wary, V.; Berg,
A.; Grafe, G.; Proksch, P. J. Nat. Prod. 2002, 65, 1598.
(b) Musgrave, O. C. J. Chem. Soc. 1956, 4301. (c) Lai, S.;
Shozuri, Y.; Yamamura, S.; Kawai, K.; Terada, Y.;
Furukuwa, H. Tetrahedron Lett. 1989, 30, 2241.
(d) Robeson, D. J.; Strobel, G. A.; Strange, R. N. J. Nat.
Prod. 1985, 48, 139. (e) Ghisalberti, E. L.; Rowland, C. Y.
J. Nat. Prod. 1993, 56, 2175.
(11) (S)-1,3-Dihydroxy-8-methyl-8,9-dihydro-5H-7-oxa-
benzocyclodecene-6,12-dione (Sporostatin, 1)
Iodine (0.52 g, 2.06 mmol) was added to a mixture of
aluminum (0.074 g, 2.76 mmol) in dry benzene. The mixture
was refluxed for 1 h, cooled to r.t., and then n-Bu4N+I–
(0.0032 g, 0.0089 mmol) and compound 10 (0.020 g, 0.688
mmol) in dry benzene (8 mL) were added. The mixture was
stirred for 45 min at 10 °C and quenched with H2O. After
acidification with 2 M HCl, the mixture was extracted with
Synlett 2009, No. 5, 790–792 © Thieme Stuttgart · New York