【作者】 杨兰；

【导师】 王成章；

【作者基本信息】 中国林业科学研究院 ， 林产化学加工工程， 2011， 硕士

【摘要】 银杏叶聚戊烯醇是由15²1个异戊烯基单元及终端异戊烯伯醇组成的线性长链化合物,聚戊烯醇为天然产物,对人体无毒、无致突变、无致畸和无致癌作用,具有明显的生理和药理作用。银杏叶聚戊烯醇大部分以乙酸酯的形式存在,少量为游离醇形式,其含量约占银杏叶干重的0.5 %² %。S-多萜醇是一类存在于动植物组织中具有光学活性的线状异戊烯基长链化合物,但末端单元为饱和的异戊伯醇。S-多萜醇是糖蛋白生物合成的关键载体,具有清除自由基、抗氧化和造血功能。银杏叶聚戊烯醇是半合成S-多萜醇的理想原料。聚戊烯醇的纯度通过高效液相色谱（HPLC）外标法确定。通过标准曲线得到的回归方程为y=1.5751x+1.1546（R²=0.9991）,y代表聚戊烯醇5个主要峰的峰面积,x代表样品中聚戊烯醇的质量,以此计算聚戊烯醇的纯度。进样量为4.6²3.3μg时,线性关系较好。本文将脱色应用于聚戊烯醇的纯化中,并对传统的聚戊烯醇纯化工艺进行了优化。通过L₉（3⁴）正交试验,确定了最佳脱色条件:聚戊烯醇粗品与石油醚固液比1:10（g/mL）,采用活性炭与凹凸棒土作为混合脱色剂,活性炭与凹凸棒土比例为1:5（g/g）,聚戊烯醇粗品与脱色剂比例1:1.2（g/g）,脱色温度70℃,搅拌脱色时间20 min。经过脱色,聚戊烯醇纯度由38.5 %提高到49.6 %,脱色过程中聚戊烯醇基本无损失。脱色后的聚戊烯醇再经过一步柱层析即可将纯度提高到90 %以上。优化的纯化方法具有方便、快捷、经济、收率高和适合工业化生产等特点。由于没有与C5合成子（（R）-4-苄氧基-1-溴-2-甲基丁烷）结构相近且带有旋光性的化合物,手性C5合成子是通过以3-甲基-3-丁烯-1-醇为原料经过酶催化的立体选择性乙酰化等几步反应来合成的。首先在相转移催化剂条件下对羟基进行苄基保护,再依次经过硼氢化反应、荧光假单胞菌脂肪酶催化下的立体选择性乙酰化反应和溴代反应合成C5合成子。在吡啶和醋酸酐作用下,高纯度的聚戊烯醇经过传统的乙酰化反应生成聚戊烯基乙酸酯。聚戊烯基乙酸酯再与C5合成子的格氏试剂在Li₂CuCl₄催化下,在无水THF中进行碳碳偶合,合成S-多萜醇苄醚。S-多萜醇苄醚在碱金属的氨溶液作用、-78℃下,脱苄基保护,可以合成S-多萜醇。更多还原

【Abstract】 Polyprenols from Ginkgo biloba L. leaves generally compose of 15 to 21 unsaturated isoprene units and are terminated by an unsaturated isoprene unit bearing a primary hydroxyl group. Polyprenols are natural products. They are not only non-toxic, non-mutagenic, non-teratogenic, and non-carcinogenic in humans but also have distinct physiological and pharmacological functions. Polyprenols mainly exist in the form of acetates and a few are in the form of free alcohols. These account for 0.5 %² % according to the dry G. biloba L. leaves. S-dolichol is a linear polyisoprene compound with a terminal unit of saturated isopropane bearing a primary hydroxyl group, which is found in the lipid fraction of animal and plant tissues. S-dolichol is the key carrier in the biosynthesis of glycoprotein, with biological functions such as free radical scavenging, antioxidation, hematopoiesis etc. Polyprenols are ideal as initial building blocks for the semisynthesis of S-dolichol.The purity of polyprenols was determined by High Performance Liquid Chromatography （HPLC） using external standard method. The regression equation obtained from the standard curve was y=1.5751x+1.1546 （R²=0.9991）, and y is the peak area of the 5 main peaks, x is the amount of polyprenols. The purity of polyprenols was calculated according to the standard curve. The linear relation between the amount of polyprenols （4.6²3.3μg） and peak area was good.Decoloration technology was applied to the purification of polyprenols, and the traditional purification process for polyprenols was optimized. L₉（3⁴） orthogonal experiment design was employed to optimize the conditions for decoloration. Decoloration of polyprenols could be achieved effectively by stirring crude polyprenols in petroleum ether （1:10, w/v） and adding mixed decolorant （activated carbon/attapulgite ratio of 1:5, w/w） with a polyprenols/decolorant ratio of 1:1.2 （w/w） for 20 min at 70℃. Decoloration applied under the optimal condition could improve the purity of polyprenols from 38.5 % to 49.6 % without loss of polyprenols. The purity could be further improved to over 90 % through only one cycle of silica gel column chromatography. This developed purification method is convenient, rapid, economical, high-yield, and suitable for industrial production, among others.Due to the lack of commercially available optically pure compounds with a similar structure, C5 synthon （（R）-4-benzyloxy-1-bromo-2-methylbutane） was synthesized from the readily available 3-methyl-3-buten-1-ol using a slightly more complex procedure involving an enzymatic enantio-resolution step. At first, the hydroxyl function of 3-methyl-3-buten-1-ol was protected with a benzyl group carried out under phase-transfer conditions. The unsaturated benzyl ether was converted to the racemic primary alcohol by a hydroboration–oxidation reaction, followed by the stereoselective acetylation and bromination.Polyprenols with high purity were conventionally acetylated with acetic anhydride and pyridine. S-dolichyl benzyl ether was synthesized using Grignard coupling reaction between polyprenyl acetates and the Grignard reagent of C5, which was carried out in THF catalyzed by Li₂CuCl₄. The S-dolichyl benzyl ether could be deprotected by reduction with alkali metal in ammonia solution at -78℃and S-dolichol can be obtained.更多还原