The Synthesis Of Paclitaxel Analogues. ¢÷ To A Diterpenoid Alkaloids Conversion Of The Synthesis Of Paclitaxel Analogues

On the basis of our previous work on the conversion of the norditerpenoid alkaloids into taxoids, the CAB synthesis approach was determined. This dissertation described further research on the key reactions of the nitrone formation and cleavage of N-C(19) bond in the modification of ring A and the CAB synthesis route. 1. Modification of ring A of C₁₉-diterpenoid alkaloidTreatment of C-nor C₁₉-diterpenoid alkaloids 14, 24 and 26 bearing oxygenated group at C-8 with NBS/HOAc led to imines 16, 25 and 27 in high yield, and further oxidation with m-CPBA did not obtained the expected nitrone but the oxaziridine 18 and compound 17. Attempt to cleave N-C(19) bond through HIO)4 or LTA oxidation of 17 failed probably due to easy oxidation of α-methoxylketone moiety.After expulsion of oxygenated group at C-8 and reduction of ketone group at C-13, the imine 40 could be prepared in moderate 62% yield and N-C(19)-seco norditerpenoid alkaloid 42 was obtained from 40 through a "one-pot" method by oxidation with m-CPBA and LTA. Because of the participation of C(3)-OH, treating imine 40 using classic Nef reaction condition did not give the expected product with ketone group at C-17 rather than a novel compound 43 isolated as blue amorphous powder. Its structure was confirmed by spectral data and chemical method. An improved Nef reaction condition was adopted to convert of the nitro compound 60being protected by TBS to give a key intermediate 62. Thus, we have successfully accomplished the ring A modification of C-nor Cig-diterpenoid alkaloid for the first time using yunaconitine as starting material through 15 steps.2. Cleavage of C(12)-C(14) bond through aromatization of ring DTreatment of compound 28 with SOCl2/Pyr\ 40% HBr and 5% NaOH/MeOH could afforded products 66, 67 > 70 and 71 instead of the expected aromatic product 29. Two C-nor C19-diterpenoid alkaloids 83 and 88 possessing a 15(16) double bond were prepared, and it was found that A 15(16) olefin 82 and 87 were easier to accomplish semipinacol rearrangement than others in which there has not this structural unit.3. Oxidation of lycoctonine-tye Cig-diterpenoid alkaloidTreatment of a lycoctonine-type alkaloid acetyllycoctonine 89 with NBS and m-CPBA at room temperature led to twelve new artificial products 90-95 and 96-101 respectively and the plausible process of the formation of these compounds was described. 4. Ninety-four norditerpenoid alkaloids and its analogues were prepared during our research; eighty-five of them were new artificial compounds. Their structures were determined by spectral data (MS, !H NMR, i3C NMR and 2D NMR) and chemical methods.