Total Synthesis Of Subincanadine F And Synthetic Studies Towards Stemoamide And Merrilactone A

This thesis describes the synthetic studies of indole alkaloid subincanadine F, stemona alkaloid stemoamide and sesquiterpene merrilactone A.Partâ… :Total Synthesis of Indole Alkaloid(±)-Subincanadine F via SmI₂-Mediated Ring Opening and Bridge-Forming Mannich Reaction.Subincanadine F was isolated by Kobayashi from the barks of a Brazilian medicinal plant and featuring a 1-azabicyclo[4.3.1]decane framework,displayed prominent in vitro cytotoxicity against murine lymphoma L1210 cells and human epidermoid carcinoma KB cells based upon the preliminary biological experiments.A strategy involving Michael addition,Pictet-Spengler cyclization and Dieckmann condensation to construct the tetracyclic core of subincanadine F was investigated and the Dieckmann condensation to construct D ring of subincanadine F was failed to achieve.Then the S_N2 and Pictet-Spengler cyclization tandem reaction was developed to construct C/D rings of subincanadine F in one pot.The bridge-containing tetracyclic framework of subincanadine F was efficiently assembled by SmI₂ mediated ring-opening followed by acid mediated Mannich reaction.The exocyclic alkene was constructed via aldol condensation then dehydration.After the removal of the protecting group the first total synthesis of subincanadine F was achieved.Partâ…¡:Concise Assembly of(+)-9a-epi-Stemoamide via DBU-Catalyzed Michael Addition of Nitroalkane.Stemoamide,one of the Stemona alkaloids,was isolated from the root of Stemona tuberosa Lour.by Xu and co-workers.The related Stemona species have been used in traditional Chinese medicine as anticough agents and insecticides. (-)-Stemoamide is composed of a perhydropyrroloazepine ring fused to aγ-butyrolactone moiety,and it contains four contiguous stereogenic centers.A strategy involving DBU-catalyzed Michael addition of nitroalkane,reductive lactamization of nitro esters and then intramolecular S_N2 ring closing to construct the tricyclic framework of stemoamide was achieved.(+)-9a-epi-Stemoamide,an epimer of stemoamide,was synthesized for the first time as a pure single compound.Partâ…¢:Synthetic Efforts towards Sesquiterpene Merrilactone A.Merrilactone A is an unique pentacyclic sesquiterpene dilactone isolated in 2000 by Fukuyama and co-workers from the Illicium merrillianum.It was identified as a potent nonpeptidal neurotrophic factor that promotes neurite outgrowth in the culture of fetal rat cortical neurons.The molecule sports seven contiguous chiral centers,of which three are quaternary and bears a highly substituted cyclopentane ring at its core. The featured B/D rings were designed to synthesis via molybdenum-mediated intramolecular hetero-Pauson-Khand reaction.(1) As a model reaction of hetero-Pauson-Khand reaction,the bicyclic monotepene natural product(+)-mintlactone has been efficiently assembled from (-)-citronellol.Key transformations include HNO₂-induced formal isopropylidene "demethanation" and molybdenum-mediated intramolecular hetero-Pauson-Khand reaction.(2) To construct the B/D rings of merrilactone A via hetero-Pauson-Khand reaction,two ring-forming sequences were investigated.A ring formed firstly then B/D rings via hetero-Pauson-Khand reaction proved to be unfruitful.B/D rings were constructed via hetero-Pauson-Khand reaction successfully and then A ring was hard to be constructed because of ring stain.(3) A "green",convenient,economical and practical protocol for borax-catalyzed thiolysis of epoxides and aziridines,aminolysis of aziridines has been developed. Borax might act as a bifuctional catalyst to be helpful to these ring-opening reactions.