ORGANIC
LETTERS
2005
Vol. 7, No. 18
3853-3855
Stereospecific Synthesis of
)-1,2-Anhydro Methyl Rocaglate
(±
Philip Magnus* and Matthew A. H. Stent
Department of Chemistry and Biochemistry, UniVersity of Texas at Austin,
Austin, Texas 78712
Received June 13, 2005
ABSTRACT
The rocaglates and analogues thereof have recently become targets for synthesis because of their potent antitumor activity. One of the major
difficulties has been the control of stereochemistry of the adjacent Ph and An groups. In this letter we show that 14 is converted into 5 as
a single stereoisomer and subsequently transformed into 1,2-anhydro methyl rocaglate 20.
−
−
The genus Aglaia (Meliaceae) is a diverse species that occurs
in tropical rain forests (Indo-Malaysian) and produces 1H-
cyclopenta[b]benzofurans as exemplified by the structure of
methyl rocaglate 11a and rocaglamide 2,1b Scheme 1. The
activity comparable to that of taxol.3 The combination of
the unusual structures and significant biological properties
has generated interest in the synthesis of 2.4 The cis
stereochemical relationship between C-3 (-Ph) and C-3a
(2) Proksch, P.; Edrada, R.; Ebel, R.; Bohnenstengel, F. I.; Nugroho, B.
W. Curr. Org. Chem. 2001, 5, 923-938. Chaidir, J. H.; Bohnenstengel, F.
I.; Nugroho, B. W.; Schnieder, C.; Wray, V.; Witte. L.; Hung, P. D.; Keit,
L. C.; Proksch, P. J. Nat. Prod. 1999, 62, 1632-1635. Dumontet, V.;
Thoison, O.; Omobuwajo, O. R.; Martin, M.-T.; Perromat, G.; Chiaroni,
A.; Riche, C.; Pa¨ıs, M.; Se´venet, T.; Hadi, A. H. A. Tetrahedron 1996, 52,
6931-6942. Ishibashi, F.; Satasook, C.; Isman, M. B.; Towers, G. H. N.
Phytochemistry 1993, 32, 307-310. Nugroho, B. W.; Edrada, R. A.;
Gu¨ssregen, B.; Wray, V.; Witte. L.; Proksch, P. Phytochemistry 1997, 44,
1455-1461. Chaidir, J. H.; Nugroho, B. W.; Bohnenstengel, F. I.; Wray,
V.; Witte. L.; Hung, P. D.; Keit, L. C.; Sumaryono, W.; Proksch, P.; Proksch,
P. Phytochemistry 1999, 52, 837-842.
Scheme 1
(3) Hwang, B. Y.; Su, B.-N.; Chai, H.; Mi, Q.; Kardono, L. B. S.;
Afriastini, J. J.; Riswan, S.; Santarsiero, B. D.; Mesecar, A. D.; Wild, N.
R.; Fairchild, C. R.; Vite, G. D.; Rose, W. C.; Farnsworth, N. R.; Cordell,
G. A.; Pezzuto, J. M.; Swanson, S. M.; Kingshorn, A. D. J. Org. Chem.
2004, 69, 3350-3358. Correction-J. Org. Chem. 2004, 69, 6156. The correct
taxonomic identity of the plant studied is Aglaia foVeolata Pannell, not
Aglaia silVestris (M. Roemer) Merrill.
(4) (a) Trost, B. M.; Greenspan, P. D.; Yang, B. V.; Saulnier, M. G. J.
Am. Chem. Soc. 1990, 112, 9022-9024. (b) Davey, A. E.; Schaeffer, M.
J.; Taylor, R. J. K. J. Chem. Soc., Perkin Trans. 1 1992, 2657-2666. (c)
Dobler, M. R.; Bruce, I.; Cederbaum, F.; Cooke, N. G.; Diorazio, L. J.;
Hall, R. G.; Irving, E. Tetrahedron Lett. 2001, 42, 8281-8284. (d) Feldman,
K. S.; Burns, C. J. J. Org. Chem. 1991, 56, 4601-4602. (e) Kraus, G. A.;
Sy, J. O. J. Org. Chem. 1989, 54, 77-83. (f) Gerard, B.; Jones, G., II;
Porco, J. A., Jr. J. Am. Chem. Soc. 2004, 126, 13620-13621. (g) Hailes,
H. C.; Raphael, R. A.; Staunton, J. Tetrahedron Lett. 1993, 34, 5313-
5316. (h) Thede, K.; Diedrichs, N.; Ragot, J. P. Org. Lett. 2004, 6, 4595-
4597. Diedrichs, N.; Ragot, J. P.; Thede, K. Eur. J. Org. Chem. 2005, 1731-
1735.
rocaglates have insecticidal activity (comparable to aza-
dirachtin),2 but more importantly, they are very potent
cytotoxic compounds when evaluated against human cell
lines. More recently, the rocaglate derivatives silvestrol 2
and episilvestrol 3 have been isolated from the fruits and
twigs of Aglaia foVeolata (Pannell) and have cytotoxic
(1) (a) Cui, B.; Chai, H.; Santisuk, T.; Reutrakul, V.; Farnsworth, N. R.;
Cordell, G. A.; Pezzuto, J. M.; Kingshorn, A. D. Tetrahedron 1997, 53,
17625-17632. (b) King, M. L.; Chiang, C.-C.; Ling, H.-C.; Fujita, E.;
Ochiai, M.; McPhail, A. T. J. Chem. Soc., Chem Commun. 1982, 1150-
1151.
10.1021/ol0513793 CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/12/2005