Studies On The Total Syntheses Of Maistemonine,Stemonamide, Isomaistemonine, Stemonamine,and Parvineostemonine

The Stemona alkaloids represent a class of polycyclic alkalodis and widely exist in Stemonaceae plant species. To date, more than130Stemona alkaloids have been isolated, and their total syntheses have attracted extensive interests of chemists due to their various categories, relatively complex structures, and biological activities. The following four parts are mainly included:1. The isolation of Stemona alkaloids from nature and the structural types of them were introduced. Based on their structural characteristics, some representative synthesis works were be described.2. A full account of the total synthesis of (±)-maistemonine,(±)-stemonamide, and (±)-isomaistemonine is presented. Two approaches have been developed to construct the basic pyrrolo[1,2-a]azepine core of the Stemona alkaloids, featuring a tandem semipinacol/Schmidt rearrangement of a secondary azide and a highly stereoselectively desymmetrizing intramolecular Schmidt reaction, respectively. To build the common spiro-y-butyrolactone, a new protocol was carried out by utilizing an intramolecular ketone-ester condensation as the key transformation. The vicinal butyrolactone moiety of (±)-maistemonine was stereoselectively introduced via a one-pot procedure involving the epimerization at C-3and carbonyl allylation/lactonization. Moreover,(±)-stemonamide was divergently synthesized from a common intermediate and (±)-isomaistemonine was obtained via the epimerization of (±)-maistemonine at C-12.3. A highly efficient TiCl4-promoted tandem intramolecular Prins cyclization/Schmidt reaction has been designed and developed to construct the azaspiro[4,4]nonane. The present tandem protocol has been employed to construct the tricyclic azaquaternary skeleton of stemonamine. The unsaturated spiro-y-butyrolactone ring was forged by a highly stereoselectively ketone-ester condensation and then the total synthesis of (±)-stemonamine was completed. 4. The first total synthesis of (±)-parvineostemonine was efficiently achieved from commercially available tropinone in11steps. The synthetic approach features a radical-mediated7-exo-trig cyclization and a stereoselective carbonyl allylation/lactonization. Especially, we firstly proposed the biomimetic transformation from parvineostemonine to another Stemona alkaloid sessilifoliamide C. And the biomimetic synthesis is currently underway in our group.