红豆杉中紫衫烷类活性成分高效诱导、分离纯化和多西紫衫醇半合成

以紫杉醇为代表的紫杉烷类化合物具有广谱高效的抗癌活性，国内外医药市场需求量大，但由于红豆杉资源的紧缺和传统加工工艺的落后，限制了紫杉烷类化合物产业化生产规模。 本项目在阐明红豆杉中紫杉烷类化合物动态变化规律的基础上，以红豆杉枝叶为原料，利用匀浆空化-酶生物转化技术、负压空化提取-负压空化快速解析技术、大孔吸附树脂AB-8 富集分离技术、连续中压正相、反相柱层析技术等创新性产业化技术对紫杉烷类化合物进行提取和纯化，建立了一次投料同时获得多个高附加值产品的紫杉烷类化合物产业化生产新工艺，并通过紫杉烷类化合物提取废料的回收利用，获得了高附加值产品β-谷甾醇，同时以提取纯化的10-DAB Ⅲ为母核，乙酰氯为多西紫杉醇侧链前体合成的氢质子来源，半合成了多西紫杉醇。 本项目工艺改进了传统的紫杉烷类化合物提取分离工艺，从红豆杉原料中获得的产品种类、产品在相同纯度下的总收率居目前国际产业化领先水平。本项目已获得国家发明专利1 项，实审3 项，获得实用新型专利6 项，发表论文12 篇，其中SCI 收录6 篇，累积影响因子15.940，EI 1 篇。

Taxanes represented by paclitaxel possess broad-spectrum and highly efficient anti-cancer activities, and are in high demand in domestic and international pharmaceutical markets. However, the scarcity of Taxus resources and the backwardness of traditional processing technologies have restricted the industrial production scale of taxane compounds.

Based on elucidating the dynamic variation rules of taxane compounds in Taxus, this project took Taxus twigs and leaves as raw materials, and adopted a series of innovative industrial technologies including homogenization cavitation-enzymatic biotransformation technology, negative pressure cavitation extraction-negative pressure cavitation rapid desorption technology, macroporous adsorption resin AB-8 enrichment and separation technology, and continuous medium-pressure normal-phase and reversed-phase column chromatography technology to extract and purify taxane compounds. A new industrial production process for taxane compounds was established, which can obtain multiple high-value-added products in a single batch feeding. Moreover, through the recycling of taxane extraction waste, the high-value-added product β-sitosterol was obtained. Meanwhile, using the purified 10-deacetylbaccatin Ⅲ as the parent nucleus and acetyl chloride as the proton source for the docetaxel side chain precursor, docetaxel was semi-synthesized.

This project has optimized the traditional extraction and separation process of taxane compounds. The product types obtained from Taxus raw materials and the total product yield at the same purity rank among the current international leading level in industrialization. Up to now, this project has obtained 1 national invention patent, 3 patents under substantive examination, 6 utility model patents, and published 12 academic papers, among which 6 are indexed by SCI with a cumulative impact factor of 15.940, and 1 paper indexed by EI.