Submitted to: Tetrahedron Asymmetry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/28/2002
Publication Date: 2/5/2003
Citation: KATO, A., ASANO, N., IKEDA, K., MOLYNEUX, R.J., WATSON, A.A., NASH, R.J., KANO, E., ADACHI, I., FLEET, G.W., DENMARK, S.E. AUSTRALINE AND RELATED ALKALOIDS: EASY STRUCTURAL CONFIRMATION AND BIOLOGICAL ACTIVITIES. TETRAHEDRON ASYMMETRY. v. 14. p. 325-331. 2003. Interpretive Summary: Eight compounds have been isolated from a plant in the pea family. The chemical structures of these compounds are very similar, differing only in their spatial, three-dimensional arrangements. However, the compounds differ in their biological activities. There has been controversy over the exact structure of some of these compounds. This manuscript describes an easy method for distinguishing between them. This will be useful in relating chemical structure to specific biological activity, in particular the way in which sugars are used in cases where genetic defects exist.
Technical Abstract: The first polyhydrroxylated pyrrolizidine alkaloid with a hydroxymethyl group at C-3 was isolated from pods of Alexa leiopetala (leguminosae) and designated alexine (1). The Australian legume Castanospermum australe is also known to produce the same structural type of pyrrolizidines. There are reports of the isolation of australine (7a-epialexine) (2)., 1-epi-australine (3), 3-epi-australine (4), and 7 epi-australine (5)from this plant to date. Their unambiguous syntheses established that the natural product reported as 5 is 2 and the published NMR data for 2 are those of 3. These confusions prompted us to unambiguously confirm the structures and biological activities of australine isomers and related alkaloids. A careful search for polyhydroxylated pyrrolizidines in seeds of C. australe led to the discovery of three new alkaloids, 2,3-diepi-australine (6), 2,3,7-triepi-australine (7), and the 2-0-B-D-glucopyranoside (8) of 3. In this paper, we report the 13C NMR full assignment of alkaloids 1-8 and the glycosidase inhibitory activities of alkaloids 2-8 together with the highly oxygenated pyrrolizidine, casuarine (9), and its 6-0-a-D-glucopyranoside (10).