ORGANIC
LETTERS
2007
Vol. 9, No. 25
5219-5222
Amaranzole A, a New N-Imidazolyl
Steroid from Phorbas amaranthus
Brandon I. Morinaka,§ Makoto N. Masuno,† Joseph R. Pawlik,‡ and
Tadeusz F. Molinski*,§
Department of Chemistry and Biochemistry and SSPPS, UniVersity of California,
San Diego, 9500 Gilman DriVe, La Jolla, California 92093, UniVersity of California,
DaVis, 1 Shields AVenue, DaVis, California 95616, and Department of Biology and
Marine Biology, Center for Marine Science, UniVersity of North Carolina Wilmington,
5600 MarVin K. Moss Lane, Wilmington, North Carolina 28403-3297
Received September 24, 2007
ABSTRACT
An unprecedented 24-N-imidazolyl steroidal alkaloid, amaranzole A, was isolated from a tropical sponge, Phorbas amaranthus. The structure
was solved by interpretation of MS, NMR, including a novel exciton-coupled CD spectrum due to an allyl imidazole, and comparison with
model compounds.
Numerous steroidal alkaloids have been isolated from plants
(e.g., solanum alkaloids)1 and amphibians (e.g., batrachotox-
ins, BTX, in Phyllobates and Dendrobates).2 In contrast,
marine-derived steroidal alkaloids are fewer in number. The
only examples are the plakinamines (dihydropyrroles from
the sponge species Plakina3a and Corticium spp.),3 cortistatins
A-D (isoquinolines from C. simplex),4 cephalostatins (from
the marine worm Cephalodiscus gilchristi),5 and related
compounds ritterazines (pseudo-dimeric pyridazines from the
tunicate Riterella tokioka).6
In our studies of antifeedant compounds from extracts
of the chemically defended Phorbas amaranthus (Order
Poecilosclerida, Class Demospongia),7 we previously re-
ported the ring-A contracted steroids, phorbasterones,8 from
nonpolar fractions of the sponge extract. Further investiga-
tions of a highly polar antifeedant fraction of P. amaranthus
extracts uncovered an unprecedented steroidal alkaloid,
amaranzole A (1). Amaranzole A is a new chemotype, a
steroid bearing a C24-N-imidazolyl group that appears to
§ University of California, San Diego.
† University of California, Davis. Present address: Westmont College,
Santa Barbara, CA 93108.
‡ University of North Carolina Wilmington.
(1) Atta-Ur-Rahman; Choudhary, M. I. In The Alkaloids: Chemistry and
Biology; Cordell, G. A., Ed.; Academic Press: San Diego, CA, 1998; Vol.
50, p 61.
(2) (a) Daly, J. W.; Myers, C. W.; Warnick, J. E.; Albuquerque, E. X.
Science 1980, 208, 1383-1385. (b) BTX and homobatrachotoxin were also
found in the feathers of passerine birds of the New Guinea highlands, e.g.,
Ifrita kowaldi: Dumbacher, J. P.; Spande, T. F.; Daly, J. W. Proc. Natl.
Acad. Sci. U.S.A. 2000, 97, 12970-12975.
(3) (a) Rosser, R. M.; Faulkner, D. J. J. Org. Chem. 1984, 49, 5157-
5160. (b) Ridley, C. P.; Faulkner, D. J. J. Nat. Prod. 2003, 66, 1536-
1539. (c) Zampella, A.; D’Orsi, R.; Sepe, V.; De Marino, S.; Borbone, N.;
Valentin, A.; Debitus, C.; Zollo, F.; D’Auria, M. V. Eur. J. Org. Chem.
2005, 20, 4359-4363 and references cited therein.
(4) Aoki, S.; Watanabe, Y.; Sanagawa, M.; Setiawan, A.; Kotoku, N.;
Kobayashi, M. J. Am. Chem. Soc. 2006, 128, 3148-3149.
(5) (a) Pettit, G. R.; Inoue, M.; Kamano, Y.; Dufresne, C.; Christie, N.;
Niven, M. L.; Herald, D. L. J. Chem. Soc., Chem. Commun. 1988, 13, 865-
867. (b) Pettit, G. R.; Kamano, Y.; Dufresne, C.; Inoue, M.; Christie, N.;
Schmidt, J. M.; Doubek, D. L. Can. J. Chem. 1989, 67, 1509-1513. (c)
Pettit, G. R.; Ichihara, Y.; Xu, J.; Boyd, M. R.; Williams, M. D. Bioorg.
Med. Chem. 1994, 4, 1507-1512 and references cited therein.
(6) (a) Fukuzawa, S.; Matsunaga, S.; Fusetani, N. J. Org. Chem. 1994,
59, 6164-6166. (b) Fukuzawa, S.; Matsunaga, S.; Fusetani, N. J. Org.
Chem. 1995, 60, 608-614. (c) Fukuzawa, S.; Matsunaga, S.; Fusetani, N.
Tetrahedron 1995, 51, 6707-6716.
(7) (a) Pawlik, J. R.; Chanas, B.; Toonen, R. J.; Fenical, W. Mar. Ecol.
Prog. Ser. 1995, 127, 183-194. (b) Hong, T. W. MS Thesis, University of
Calfornia, Davis, 1997.
(8) Masuno, M. N.; Pawlik, J. R.; Molinski, T. F. J. Nat. Prod. 2004,
67, 731-733.
10.1021/ol702325e CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/09/2007