Analgesic Lappaconitine Bla Structural Modification, As Well As The Fat Ring Ether Oxidation Reaction Of Lactone,

This dissertation includes mainly two sections: Moification of the analgetica lappaconitine and crassicauline A; The research of the key reaction in the convertion of aliphatic cyclic ether into lactone.1. Modification of lappaconitine and crassicauline AThe Modification of lappaconitine was emphasized on the N atom position. Oxidation of 1 with NBS/HOAc at different equivalent gave rise to imine 3 and N-deacetylated compound 4, respectively. An unexpected interesting product 5 was also achieved during the preparation of imine 3, e.g. with the formation of imine, aromatic bromation of lappaconitine happened simultaneously. Oxidation of compounds 7 and 8 without C(4)-aromatic ether group led to imine 9 and 10 in lower yield. It proved lappaconitine having aromatic ester group at position 4 was converted to imine more readily. According to analogical method, imine 13 and N-deacetylated 14 from crassicauline A were conveniently achieved. An undesired lactam 15 was also isolated from reaction residue.The derivatives of crassicauline A at position 8 and 14 were prepared by treating 20 or 27 as materials with different acylating or alkylating agents. Meanwhile, several intresting co-products were synthesized in the reactions.2. A successful access to the conversion of aliphatic cyclic ether into lactone was developed.The desired derivative 4 having alphitic cyclic ether structure from the diterpenoid was obtained by treating 1 as starting material in three steps involving methane sulfonylation, semipianol rearrangement with NaOH/DMF and SOCl₂ aromatization in 22% overall yield. The oxidation method ofC1O3/HOAC and PCC led to complex results without significant compoundisolated. To our surprise, a novel oxidative product 5 but unexpected lactone 6was obtained by treating 4 with R.UO4. After protection of hydroxy group,compound 7 obtained continued to react with R.UO4 and gave rise toN-deacelytaed compound 8 only. It is evidently due to the presence of N atom.We chose the diterpenoid maoecrystal A without possessing N atom asstarting material alternatively. After catalyzed hydrolation and acetylation ,successful preparation of 11 was achieved readily. Oxidation of 11 with R.UO4gave rise to the expected lactone 12 in 52% yield. The structure of 12 wasestablished on the basis of the 2D-NMR spectra. This development is essentialfor us to push forward to the next stage.In the course of our research mentioned above, total 35 new compounds were prepared from the diterpenoids and the nordilerpenoid alkaloids. Their structure were determined by spectral data (MS, 1D-NMR, 2D-NMR) and chemical methods.