THE ABSOLUTE-CONFIGURATION OF TRILOBACIN AND TRILOBIN, A NOVEL HIGHLYPOTENT ACETOGENIN FROM THE STEM BARK OF ASIMINA-TRILOBA (ANNONACEAE)

Trilobacin (1) is the only previously reported Annonaceous acetogenin with the erythro relative configuration between the adjacent bis-tetra hydrofuran (THF) rings. The relative configuration in the adjacent bis -THF moiety of 1 was corrected to threo/trans/erythro/cis/threo from C -15 to C-24, and the absolute configuration was determined as 4R, 15R, 16R, 19R, 20S, 23R, 24R and 36S by advanced Mosher ester methodology and the COSY and NOESY spectral analyses of its 4,24-diacetate (1a). F urther investigation of the EtOH extract of the stem bark of the paw p aw tree, Asimina triloba, monitoring for bioactivity by brine shrimp l ethality, led to a novel acetogenin, trilobin (2). Spectral and chemic al methods identified 2 as a 4-deoxy-10-hydroxy isomer of 1. The absol ute configuration of 2 was determined as 10R, 15R, 16R, 19R, 20S, 23R, 24R, and 36S by analyses of its Mosher ester derivatives. 2 was selec tively cytotoxic among three human solid tumor cell lines with over a billion times the potency of adriamycin.