Total Synthesis Of Scalarane Sesterterpenoid Marine Natural Products And Simultaneous Dehalogenation And Hydrogenation Of Halogen-Heteroaromatic Aldehydes

This research project mainly focused on three parts.(1) Total synthesis of marine natural products12,18-di-epi-scalaradial and its derivatives;(2) Total synthesis of marine natural products16-deacetoxy-12-epi-scalarafuran-acetate and its derivatives;(3) Simultaneous dehalogenation and hydrogenation of halogen-heteroaromatic aldehydes.In the first section, the key intermediate methyl ent-isocopalate in which the C-ring was successfully constructed was synthesized from commercially available (-)-sclareol using two different methods. After stereoselective epoxidation, ring opening rearrangement of the epoxide, oxidation of the secondary alcohol and then reduction, methyl ent-isocopalate was converted to compound43with the correct chiral center on C-12. We then successfully constructed the chiral center on C-13and D-ring via intermolecular Diels-Alder reaction of compound48and DM AD. However, it was difficult to oxidize compound53to form the corresponding aldehyde after several attempts and further synthesis is still going on.In the course of continues study on the oxidation of dihydroxy functional group into aldehyde, we synthesized key intermediate62bearing two aldehyde groups. Finally, diterpene (+)-Isoagatholactone was gained in linear13steps with7.2%overall yield.The second section described the first total synthesis of scalarane sesterterpenoid marine natural product16-deacetoxy-12-epi-scalarafuran-acetate in linear22steps with overall yield of3.8%using (-)-sclareol as starting material. This method provided potential synthetic access to various scalarane sesterterpenoids with the oxygenation functional group appeared at the C-12position using intramolecular Diels-Alder reaction as a key step.The last section communicated a mild and efficient method for simultaneous dehalogenation and hydrogenation of halogen-heteroaromatic aldehydes. The method was performed using PdCl2as the catalyst, sodium acetate as the base and methanol as the solvent under atmospheric pressure of hydrogen. The advantage of the present method was in terms of low catalyst loading, ordinary pressure of hydrogen, low temperatures, and short reaction times.