The Annonaceous acetogenins, that are endemic to certain plants of the Annonaceae, are of much interest especially due to their unique structural features and their significant cytotoxic, antitumor, pesticidal, antiinfective and antifeedant activities. More than 200 compounds belonging to this family have been isolated to date, and most of them posses one or more tetrahydrofuran rings, together with a terminal α, β-unsaturated γ-lactone unit on a C-35 or C-37 long carbon chain. In addition to this major group of acetogenins, there are several congeners bearing an epoxide group in place of the tetrahydrofuran ring. Herein, we report total synthesis of three mono-tetrahydrofranyl acetogenins and two epoxide containing acetogenins. A synthetic study on a nonadjacent bis-tetrahydrofuran acetogenin, 4-deoxygigantecin is now underway. 1. Synthesis of solamin (2) and reticulatacin (3) A total synthesis of the natural products, solamin (2) and reticulatacin (3) is described. The monotetrahydrofuran moiety 9 of 1 and 2 was constructed by a fifteen-step reaction sequence, starting from lauryl bromide (4) and 2-propyn-1-ol (5). A palladium-catalyzed cross coupling reaction of 9 and γ-lactone 10 or 11, and subsequent three-step sequence led to 2 and 3, respectively. 2. Synthesis of (10R)- and (10S)-corossoline (12) A convergent stereoselective total synthesis of (10R)- and (10S)-corossoline (12) has been performed via a multi-step process. Comparison of the mp, [α]D, IR, and NMR data of both synthetic materials with those reported for natural corossoline did not allow for the strict determination of the configuration at the C-10 hydroxy group of 12. However, a slight chemical shift difference at the C-10 methine proton was observed in the ^1H-NMR spectra of the corresponding tris(S)-MTPA esters of synthetic (10R)- and (10S)-12, indicating that if the tris(S)-MTPA ester of natural one is available, the stereochemistry at the C-10 hydroxyl group of corossoline will be established. 3. Synthetic studies on 4-deoxygigantecin (22) Synthetic studies on 4-deoxygigantecin (22) is described. The bistetrahydrofuran moiety 27 of 22 was constructed by an eleven-step reaction sequence, starting from 23 and 24. A palladium-catalyzed cross coupling reaction of 27 and γ-lactone 28 afforded 29. Studies directing toward a total synthesis of 22 is now underway. 4. Synthetic studies on epoxyacetogenins. (i) Synthesis of (20R, 21S, 37S)- and (20S, 21R, 37S)-epoxyrollin A (30) A synthesis of two possible diastereoisomers (20R, 21S, 37S)- and (20S, 21R, 37S)-30 corresponding to the epoxy lactone that has been proposed for epoxyrollin A, a stuructural representive of biosynthetic precursors of tetrahydrofuran annonaceous acetogenins, is described. The ^<13>C-NMR and tandem mass spectral data of the synthetic samples were not in accordance with those recorded for natural epoxyrollin A. Consequently, the structure of epoxyrollin A needs to be revised. (ii) Synthesis of (15S, 16R, 19S, 20R, 36S)-diepomuricanin (31) An eleven-step reaction sequence starting from enantiomerically pure (-)-muricatacin (6) afforded the key intermediate 38, which was then converted to (15S, 16R, 19S, 20R, 36S)-diepomuricanin (31) via introduction of an acetylene unit and a coupling reaction with iodo lactone synthon 41.
