Investigation On The Phytoehemistry Of The Plant Aconitum Pieounense And The Conversion Of The Norditerpenoid Alkaloids Into Taxoids

In this dissertation the following two sections are included.1. Investigation on the phytoehemistry of the plant Aconitum pieounense To our knowledge, no phytochemical investigation of this plant had been undertaken. Seven new diterpenoid alkaloids, piepunensine A, piepunensine B, 18-acetylcammaconine, piepunendine A, piepunendine B, piepunendine C and piepunine, together with nine known alkaloids, yunaconitine, talatisamine, pengshenine B, aconosine, talatizidine, deltaline, 19-one talatisamine, methyllycaconitine and delsemine A, have been isolated from the roots of Aconitum pieounense. Their structures were elucidated on the basis of spectral data (1D-, 2D-NMR and HR-MS) and chemical methods. Furthermore, two new norditerpenoid alkaloids were identified according the combinated NMR and ESIMS spectrum.This research has firstly found a new aconitine-type diterpenoid alkaloid containing both 19-OH and N-acetyl groups. And piepunine is a novel atisine-denudatine bisditerpenoid compound.2. Studies on the conversion of the norditerpenoid alkaloids into taxoids1) Construction of [6+8+6] ring system using semipinacol rearrangementIn this section, a new conversion approach to toxids using deltaline (3) as the starting material via the semipinacol rearrangement of the ring C was proposed through the routes ABC and CAB. Under the conditions (NaOH/DMF, NaI/DMF), compound 10, 39, 43, 44, and 52 didn't obtain the expected semipinacol rearrangement products, probably due to the special hindrance derived from the 1α-OCH₃. To attempt the Grob fragmentation followed by the modification of ring C showed that it was difficult to chloro-substitute for 10-OH after introducing the 12-hydroxyl group. However, there was no influence on Grob fragmentation when substitutity at C-14 was changed.2) Construction of [6+8+6] ring system by aldol cendensationUsing a new method developed by us, NBS oxidation-hydrolysis of 51 obtained the O, O-demethenyl compound 82. With compound 85, 89, and 90 as substrate, respectively, aldol condensation under conditions (NaOH/Na₂CO₃, NaOH/MeOH) only led to two six-membered ring B compounds rather than the expected eight-membered ring compound 86 and 91. This illustrated C-6 perferred to emerge negative ion to attack C-8, possibly because of the existence of double bondâ–³⁵⁽¹¹⁾.3) Other reactions concerning norditerpenoild alkaloids(1) Treatment of 36, 51, and 9 with Boc₂O/Pyr, gave the 10, 12-carbonate compound 97, 98, and 99, respectively, probably due to the intramolecular transesterification process.(2) When 106 and 105 was refluxed with dioxane/H₂O, the 7, 17-seco norditerpenoid alkaloid 109 and 111 was obtained, respectively. It's a new cleavage of the 7, 17-bond of the aconitine-type diterpenoid alkaloids. This showed that the formation of tetrahydrofuran ring (C₆-C₅-C₄-C₁₈-O) promoted the cleavage of the 7, 17-bond in 105 and 106.(3) Treatment of 119 with concentrate aqueous ammonia for 66 h, a N, 19-seco compound 122 was obtained. This is a new method to break N-C₁₉ bond of the lycoctonine-type diterpenoid alkaloids.Eighty-two new or novel artificial compounds among total 90 norditerpenoid alkaloids were prepared in the course of this study. Their structures were determined by spectral analysis (IR, MS, HR-MS, ¹H- and ¹³C-NMR, DEPT, NOEDS, ¹H-¹H COSY, HMQC and HMBC) and chemical methods.Having greatly enriched the research of chemistry of the 10-OH C₁₉-diterpenoid alkaloids as well as developed several excellent reactions, this dissertation provided a new plan for conversion of the norditerpenoid alkaloids into taxoids with tedious exploratation and a solid foundation for further construction of the [6+8+6] ring system.