ORGANIC
LETTERS
2000
Vol. 2, No. 23
3683-3686
Total Synthesis of
(+)-7-Deoxypancratistatin from Furan
a
Jose´ Luis Acen˜a, Odo´n Arjona,* M Luisa Leo´n, and Joaqu´ın Plumet*
Departamento de Qu´ımica Orga´nica I, Facultad de Qu´ımica, UniVersidad
Complutense, 28040 Madrid, Spain
Received September 14, 2000
ABSTRACT
A new total synthesis of (+)-7-deoxypancratistatin 1 has been accomplished in 19 steps (8% overall yield) from two readly available compounds,
furan and trans-1,2-bis(phenylsulfonyl)ethylene.
The use of Amaryllidaceous plant extracts for medicinal
purposes dates back to at least the fourth century,1 and a
large number of alkaloids which possess a wide spectrum
of biological activities have been isolated from these species.
Among them, pancratistatin, narciclasine, lycoricidine, and
7-deoxypancratistatin constitute an emblematic group (Figure
1).2
In the case of 7-deoxypancratistatin 1,8 this compound has
been shown in in vitro antiviral assays to exhibit a better
therapeutic index than pancratistatin 2 due to decreased
toxicity.3f
To the best of our knowledge, six total syntheses of (+)-
7-deoxypancratistatin, 1, have been reported to the date.9 In
(2) For a review on the Amaryllidaceae alkaloids, see, for instance: (a)
Martin, S. F. In The Alkaloids; Brossi, A. R., Ed.; Academic Press: New
York, 1987; Vol. 30, pp 251-376. (b) Lewis, J. R. Nat. Prod. Rep. 1993,
10, 291. (c) Lewis, J. R. Nat. Prod. Rep. 1995, 12, 339. (d) Polt, R. L.
Amarillidaceae Alkaloids with Antitumor ActiVity. Organic Synthesis:
Theory and Application; Hudlicky, T., Ed.; JAI Press: Greenwich, CT, 1996;
Vol. 3, pp 109-148. (e) Lewis, J. R. Nat. Prod. Rep. 1996, 13, 171. (f)
Lewis, J. R. Nat. Prod. Rep. 1998, 15, 107. (g) Hoshino, O. In The
Amaryllidaceae Alkaloids . The Alkaloids, Vol. 51; Cordell, G. A., Ed.;
Academic: San Diego, CA, 1998. (h) Lewis, J. R. Nat. Prod. Rep. 1999,
16, 389.
(3) See, for instance, ref 2b and the following: (a) Cerotti, G. Nature
1967, 11, 595. (b) Jime´nez, A.; Santos, A.; Alonso, G.; Va´zquez, D Biochim.
Biophys. Acta 1976, 425, 342. (c) Pettit, G. R.; Gaddamidi, V.; Herald, D.
L.; Singh, S. B.; Cragg, G. M.; Satgawa, Y. J. Chem. Soc., Chem. Commun.
1984, 1693. (d) Pettit, G. R.; Gaddamidi, V.; Herald, D. L.; Singh, S. B.;
Cragg, G. M.; Schmidt, J. M.; Boettner, F.; Williams, M.; Satgawa, Y. J.
Nat. Prod. 1986, 49, 995. (e) Pettit, G. R.; Cragg, G. M.; Singh, S. B.;
Duke, J. A.; Doubek, D. L. J. Nat. Prod. 1990, 53, 176. (f) Gabrielsen, B.;
Monath, T. P.; Huggins, J. W.; Pettit, G. R.; Kirsi, J. J.; Schubert, E. M.;
Dare, J.; Ussery, M. A. J. Nat. Prod. 1992, 55, 1569.
(4) Ghosal, S.; Singh, S.; Kumar, Y.; Srivastava, R. S. Phytochemistry
1989, 28, 611.
(5) Ghosal, S.; Lochan, R.; Ashutosh, K. Y.; Srivastava, R. S. Phy-
tochemistry 1985, 24, 1825.
Figure 1.
The unique structural feature of these compounds with a
phenanthridone skeleton and four or six contiguous stereo-
genic centers in the C-ring together with their promising
biological activities (including antineoplasic,3 growth regula-
tory,4 mitogenic,5 and antimitotic6) have made them attractive
synthetic targets.7
(6) Evidente, A.; Arigoni, O.; Liso, R.; Calabrese, G.; Randazzo, G.
Phytochemistry 1986, 25, 2739.
(7) See refs 2b and 2f. See also: Rigby, J. H. Synlett 2000, 1. In
particular, see p 10.
(1) Hartwell, J. L. Lloydia 1967, 30, 379.
10.1021/ol000268v CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/14/2000