Absolute Stereochemistries of Sylvaticin and 12,15-cis-Sylvaticin, Bioactive C-20,23-cis Non-adjacent Bistetrahydrofuran Annonaceous Acetogenins, from Rollinia mucosa

Abstract

A new acetogenin, 12, 15-cis-sylvaticin (2), and its stereoisomer, sylvaticin (I), a known acetogenin whose stereochemical structure has remained unsolved until now, were isolated, using activity-directed fractionation, from the leaf extracts of Rollinia mucosa (Jacq.)Baill.(Annonaceae). 1 is cis at C-20, 23 and trans at '2-12, 15; 2 is cis at C-20, 23 and at C-12, 15.A key step in solving their absolute stereochemistries was the determination of the relative configurations (cis or trans) of their 1, 4-diols; this was achieved by a new procedure using the pattern recognition of the NOSEY spectra of their 1, 4-diol formaldehyde acetal derivatives ( l b and 2b).Both 1 and 2 showed potent and selective cytotoxicities, against the A-549 lung cancer and the PACA-2 pancreatic cancer, in a panel of six human solid tumor cell lines.Annonaceous acetogenins have attracted considerable attention as a rapidly growing class of new compounds; these natural polyketides, among other significant bioactivities, have excellent potential as new antitumor agents.'Structurally, most of the acetogenins found to date may be classified into three major groups, i.e., the mono-tetrahydrofuran (THF), adjacent his-THF, and nonadjacent bis-THF subclasses.The last is also the most recent subclass and, so far, has about 20 members; some of them, e.g., bullatalicin, show promising in vivo antitumor efficacy although their potencies are less than those of the adjacent his-THF compounds.2The work described in th~s paper reports, for the first time, two rare compounds (1 and 2) in this subclass which have been confirmed to possess acis-THFring at their respective C-20, 23 positions.Sylvaticin (1) and 12, 15-cis-sylvaticin (2), along with two known acetogenins, bullatalicin3 and muricatetrocin B,4 were isolated, using fractionation directed by brine shrimp lethality tests (BST), from the leaf extracts of Rollinia mucosa (Jacq.)Baill., a tropical fruit tree