Asymmetric Synthesis Of Marine Scalaranic Sesterterpenoids Containing Potential Biological Activities

Scalaranic sesterterpenoids is a kind of marine secondary metabolites with good biological activities. Studies have shown that the functional groups at the C12?16?19?20 position of these compounds will impact their biological activities to a large extent. This dissertation mainly focused on the asymmetric total synthesis of scalarane sesterterpenes containing potential biological activities. The primary coverage includes three aspects of studies:setereoselective synthesis of 16-deacetoxy-scalarafuran, (+)-scalarolide and their analogs; synthesis of sesterstatins 4/5 and scalarafuran; research on the synthesis of sesterterpenes containing isofuran structure.1. setereoselective synthesis of 16-deacetoxy-scalarafuran, (+)-scalarolide and their analogs:Methyl ent-isocopalate was synthesized through eight steps with sclareol as the strating material.16-deacetoxy-scalarafuran, (+)-scalarolide and their analogues were synthesized through three key steps:ring-opening rearrangement of epoxide under base condition to the introduction of the hydroxyl at C12; stereoselective intermolecular Diels-Alder Addition; one-pot?-butenolide and furan formation. Aromatization tetracyclic compound was obtained through intramolecular Diels-Alder reaction. In addition, nearly thirty new compounds were synthesized through the two routes, which supply good precursors and designing line for scalarane sesterterpenes of marine natural product with good biological activity.2. Synthesis of sesterstatins 4/5 and scalarafuran:Tricyclic compound methyl ent-isocopalate was still used as the starting intermediate, the configuration of hydroxyl at C12 was inverted first, one carbon elongation of enal?-25 was accomplished by Wittig olefination. In the end, sesterstatins 4/5 and scalarafuran were synthesized through intramolecular reductive Heck cyclization. The relative configuration of sesterstatin 4 was confirmed by X-ray diffraction. It has supported an efficient method for the synthesis of natural and unnatural compound containging furan or other aromatic structure through reductive Heck reaction. Besides, we still obtained new compounds containing furan moieties, which will be good precursors for the synthesis of sesterstains.3. Research on the synthesis of sesterterpenes containing isofuran structure:Primary research was done for the synthesis of sesterterpenes containing isofuran structure. The aldehyde?-7 was obtained followed by the introduction of the furan ring and the achievement of epoxidation of olefin. In the end, primary study was done on the cyclization of sesterterpenes containing isofuran under the conditions of Lewis acid.