Isoltion and Structure of Rollinisation 2: A New Cell Growth Inhibitory Acetogenin from Rollinia mucosa

aeEPILU -A new cell growth inhibitory acetogenin, designated mlliniastatin 2. has k e n isolated fmm seeds of the South American Rollinia mucosa (Annonaccae) and its structure determined.A diasareomeric relationship for rolliniastatin 1. mlliniasratin 2, and asimicin was proposed.Thc Rollinia genus (Annonaceac) is composed of some 65 species occurring principally fmm Central America to Argentina.Thr few species so far examined (chemically) fmm each of the Annona; Asimina.Rollinia, and Uvnria genera have been found m contain members of a new class of biologically active bistcmhydmfurans.Ourcrysral structure determination of mlliniastatin 12 pmvided the fmt definitive srmctun in this new series.3-10By x-ray nystzllography, the relative stereochemistry of mlliniastatin 1 was established as 4s'.15s'.16S*, 19R*, 20R*, 23S*, 24P.and 36111.2Asimicin, recently isolated fmm Asimina friloba?apparently differs fmm mlliniasudn I in its configuration at one or more of the c h i d c e n w associated with the bis-terr.khydrofuransystem Funher detailed fractionation of a hcxanc extract of Roliinia mucosa seeds has led us to uncover companions of rolliniastatin 1, including asimicin and a new diasterenmer of mlliniastatin 1. named mlliniastatin 2.Isolation of rolliniastatin 2 was effected by consecutive applications of solvent partitioning, flash chmmatography on silica gel, high-speed countercurrent distribution WCCD)I' with a multilayer mil planet centrifuge,12 column chromatography (LiChrom Si60).and W y hplc (semiprepmtivf with Panisill0 silica gel followed by analytical with Partisil5 silica gel) with the solvent system hexane -ethyl ethermethanol.With a hplc flow rate of 1.5 d m i n , emergence times (mi@ wen: mlliniasutin 1. 6.17; asimicin.6.57; rolliniaslatin 2. 6.70.High resolution sp-sims analysis of mlliniastatin 2 pmvided molecular formula C37H,&7 (mlz 623.4885; calcd for C37H6607 + H, 623.4866).The uv. ir. and eims spectra of rolliniastatin 2 wen similar w those reported for rolliniastatin 1.2 asimicin,g and 14-hydroxy-25-desoxyrollinicin.9By thin-layer chmmamgraphic comparison in dichloromethanemethanol (19:1), mlliniastalin 2 was hardly distinguishable