125(P-66) TaxinineからTaxol analogsへの変換 : Taxinine誘導体の化学反応性(ポスター発表の部)

• 堀口 透

  東北大院農・応生科

• 清田 洋正

  東北大院農・応生科

• 程 潜

  東北大院農・応生科

• 折谷 隆之

  東北大院農・応生科

書誌事項

タイトル別名

• 125(P-66) Conversion of Taxinine to Taxol analogs : Chemical reactivity of Taxinine derivatives

抄録

Currently, diterpenoid paclitaxel (faxol^[○!R] 1) is regarded as a powerful therapeutic drug for cancer chemotherapy. 1 exhibits potent antitumor activity against various cancers that have been ineffectively treated by existing chemotherapeutic drugs, and 1 have been approved by the FDA for the treatment of advanced ovarian cancer and breast cancer. Recent studies have shown that treatment for various types of advanced solid cancers with paclitaxel and docetaxel often insults in the emergence of multi-drug resistance (MDR). Thus, it is important to explore new taxoids either with improved activity against various classes of tumors, especially against drug-resistant human cancers. Here we report the methods to convert taxinine, abundantly available from the Japanese yew leaves, to a new 2-m-azido-1,7-deoxybaccatin III analog,which would be an active substrate for the tublin depolymerization test as well as 1. We also report that the biomimetic hydroxylation of C-1 position of 2-deacetoxy-taxinine J derivative (2d) had been successfully achieved by a simple chemical oxidation using dimethyl-dioxirane (DMDO), leading to the 1β-hydroxy-4α, 20-epoxide (26) and its 4β-isomer (27). This method could not be applied for 2-acetoxy-taxoids. In addition, it was found that the change of reaction temperature could control the regioselectivity of the epoxidation between the endo- and exo-double bonds of 2-deacetoxytaxinine J (2d) with m-CPBA. Attempts of biomimetic construction of the D-ring of taxol from the 4 β, 20-epoxy-5-mesyl taxoids (17) with Lewis acid mediated reaction were unsuccessful. While the same condition could convert 22-bromo-4 β, 5β-epoxy taxoid (20) to 4, 22-spirotaxoids (21) as a sole product. These result suggest that the nucleophilic trap of carbocation (III) at 5-position by water would be prior to that at 4-position, that is, it is difficult to demonstrate the proposed biosynthetic pathway of D-ring by a synthetic method.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 42 (0), 745-750, 2000

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390001206078413312
• NII論文ID: 110006682027
• DOI: 10.24496/tennenyuki.42.0_745
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可