The Annonaceous acetogenins, those are endemic to certain plants of Annonaceae, are of much interest due to their unique structural features and their significant cytotoxic, antitumor, pesticidal, antiinfective, and antifeedant activities. More than 350 compounds belonging to this family have been isolated to date, and most of them posses one or more THF rings, together with a terminal α,β-unsaturated γ-lactone unit on C-35 or C-37 long carbon chain. In addition to this major group of acetogenins, there are several congeners bearing THP rings in place of the THF ring. Herein, we wish to report synthesis studies of two mono-THF acetogenins and THP containing acetogenin. 1. A total synthesis of cis-solamin (1a) A convergent total synthesis of cis-solamin (1a) and its diastereomer (1b) was accomplished using VO(acac)_2-catalyzed diastereoselective epoxidation followed by cyclization of bis-homoallylic alcohol (2a) as the key step. By comparison of the optical rotation of two possible diastereomers, it is suggested that the absolute configuration of natural cis-solamin is 1a. 2. Synthetic studies on reticulatain-1 (7) Synthetic studies on two possible diatereomers of reticulatain-1, 7a and 7b is described. The THF ring moiety was constructed using Sharpless asymmetric epoxidation, dihydroxilation, and Mitsunobu inversion as the key steps. Sonogashira cross coupling reaction of THF ring moiety with γ-lactone part afforded enyne. Studies directing toward total synthesis is underway. 3. Synthetic studies THP ring moiety of mucocin (16) Synthetic studies on THP part of mucocin (16) is described. The THP ring moiety was constructed using alkoxy palladation as the key step. Further studies is now in progress to examine diastereoselective THP ring formation.
