synthesis of a highly functionalized triquinane studies towards a total synthesis of subergorgic acid and its analogues合成的一个高度功能化triquinane研究对总subergorgic酸及其类似物的合成.pdf

Molecules 2000, 5, 674-698 molecules ISSN 1420-3049 Synthesis of a Highly Functionalized Triquinane: Studies Towards a Total Synthesis of Subergorgic Acid and Its Analogues Veljko Dragojlovic Oceanographic Center, Nova Southeastern University, 8000 North Ocean Drive, Dania, 33004, USA Tel.: (954) 262-8332, Fax: (954) 262-3931, E-mail: veljko@ Received: 14 March 2000 / Accepted: 14 April 2000 / Published: 20 April 2000 Abstract: Reaction of enone (11) with the bifunctional Grignard reagent (7) in the presence of copper(I) bromide – dimethyl sulfide, followed by intramolecular alkylation of the resul- tant chloroketone (15) gave the tricyclic ketone (12). The tricyclic ketone (12) was trans- formed into the angular triquinane dienedione (9) by means of an 8-step sequence. Keywords: Subergorgic acid, sesquiterpenoid synthesis, methylenecyclopentane annulation, bifunctional reagents, triquinane synthesis. Introduction Chemistry of triquinane natural products has been an area of extensive synthetic studies since the mid-1970s [1-4]. Subergorgic acid is an angular sesquiterpene triquinane with a silphiperfolane skele- ton (1) [5,6]. It has been shown that subergorgic acid (2) exhibits cardiotoxic activity [5], anticholin- esterase activity [7], and activity against Soman toxicity in mice [8]. An access to triquinane natural products has been achieved by means of bifunctional conjunctive reagents [9]. The bifunctional reagent (7), developed by Piers’ group [10,11], corresponds to the 1- 2 4 2 butene d ,a -