CN1060476C - 一种制备紫杉醇的新方法 - Google Patents

一种制备紫杉醇的新方法 Download PDF

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CN1060476C
CN1060476C CN98110822A CN98110822A CN1060476C CN 1060476 C CN1060476 C CN 1060476C CN 98110822 A CN98110822 A CN 98110822A CN 98110822 A CN98110822 A CN 98110822A CN 1060476 C CN1060476 C CN 1060476C
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taxol
raw material
present
aril
torreya
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CN1197796A (zh
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陈振德
郑汉臣
张虹
王洪泉
李金昌
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Second Military Medical University SMMU
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Abstract

本发明提供一种制备紫杉醇的新方法，以红豆杉科榧属植物(Torreya)的假种皮为原料，经乙醇提取、硅胶柱层析、高效液相色谱柱分离可得到紫杉醇。本原料紫杉醇的含量是现用原料红豆杉科红豆杉属植物叶和树皮含量的2倍，且利用的是加工种子后的废弃物假种皮，因而不会破坏植物资源。本发明降低了制备紫杉醇的成本，扩大了其原料的来源，且保护了植物资源。

Description

一种制备紫杉醇的新方法
本发明涉及医药领域，特别是一种制备紫杉醇的新方法。
紫杉醇是一种治疗卵巢癌、转移性乳腺癌、肺癌、头部及颈部肿瘤、恶性黑色素瘤和淋巴肉瘤的有效药物，早在1992年美国食品药品管理局(FDA)就批准上市。现已有40多个国家批准紫杉醇上市．紫杉醇是继阿霉素及顺铂后最热点的新抗癌药。现在制备紫杉醇通常用红豆杉科红豆杉属(Taxus)植物的叶和树皮作原料，其紫杉醇含量在万分之二以内，因而制备的成本高，价格昂贵，大大限制了扩大临床应用，并会严重破坏红豆杉植物资源。
本发明的目的是提供一种制备紫杉醇的新方法，关键是选用含量高、易于得到的原料制备紫杉醇，以降低成本，保护植物资源。
本发明是应用红豆杉科榧属植物(包括榧树Torreya grandis、九龙山榧T．jiulongshanensis、长叶榧T．jackii、巴山榧T．frgesii、云南榧T．yunnanensis以及香榧T．grandis cv．merrillii等栽培品种)的假种皮作为制备紫杉醇的原料，其优点在于本原料榧属植物的假种皮为加工种子后的废弃物，大约占种子鲜重的60％，其紫杉醇含量较红豆杉高出一倍，达万分之四。我国每年约有40～100万kg假种皮，用其制备紫杉醇，不仅充分利用了资源，降低了成本，而且起到了保护植物资源的作用。
本发明制备紫杉醇的方法基本与现有用红豆杉科红豆杉的叶和树皮为原料的制备工艺相同。以红豆杉科榧属植物的假种皮为原料，经乙醇提取、硅胶柱层析、高效液相色谱柱分离等步骤，可得到紫杉醇。制备步骤详见实施例。
实施例    香榧假种皮2kg，60℃干燥，粉碎过20目筛，用95％乙醇10kg分3次(4kg、3kg、3kg)室温浸泡，每次浸泡3天，将3次浸泡液分别用布氏漏斗过滤后，合并滤液。用旋转薄膜蒸发仪减压回收乙醇后，浸膏加水1000ml。此加水浸膏先用石油醚(60～90℃)3000ml分3次(1200ml、900ml、900ml)萃取；母液再用氯仿1500ml分3次(500ml、500ml、500ml)萃取，合并氯仿提取液，用旋转薄膜蒸发仪减压回收氯仿。残留物用硅胶H拌样，上硅胶H层析柱，用氯仿∶无水乙醇(95∶5)作展开剂，硅胶柱层析分离，收集与紫杉醇相同硅胶G薄层层析板检测斑点的流份。回收展开剂，用70％乙醇水溶液重结晶2次。重结晶样品通过反相高效液相色谱柱分离，流动相为65％甲醇水溶液，收集紫杉醇部分，回收溶剂，得紫杉醇纯品。此化合物：m．p．212～215℃：FABMS M+ m／e：853；λmax(MeOH)：227nm；IR(KBr)：3400～3500(OH，NH)，1730(酯)、1660(酰胺)cm—1：1HNMR(CDCl3)和13CNMR(CDCl3)见附表。结构无误，确证为紫杉醇。
上述实施例中的符号表示如下：m．p．—熔点，FABMS M+ m／e—快原子轰击质谱分子离子峰，λmaxz(MeOH)—紫外可见分光光谱最大吸收峰，IR(KBr)一红外光谱，1HNMR(CDCL3)—氢核磁共振谱，13CNMR(CDCl3)—碳核磁共振谱。
附表样品1H和13C核磁共振化学位移值与文献比较
 H 样品δ[J] 文献[J] C 样品δ   文献δ
 1-0HH-2H-34-OAcH-5Ha-6Hb-6H-77-OHH-1010-OAcH-13Me-16Me-17Me-18Ha-20Hb-20H-2＇H-3＇3＇-NHo-Ph1m-Ph1p-Ph1o-Ph2m-Ph2p-Ph2o-Ph3m-Ph3p-Ph3  2.07bs5.67d(7.0)3.79d(1.0)．d(7.0)2.18s4.94d(8.5)2.49d(14.8)1.86d(14.6)4.37d(6.6).d(10.9)2.48bs6.26s2.21s6.20g(1.5,t(9.1)1.09s1.22s1.79d(1.6)4.30d(1.1),d(0.8),d(8.4)4.20d(1.0),d(8.4)4.78d(2.7)5.78d(2.8),d(8.8)7.11d(3.8)8.13d(1.3),d(8.4)7.52cm7.61t(1.4),d(7.4)7.48cm7.43cm7.35t(7.4)7.74d(1.2),d(3.3)7.40cm7.48cm  1.98bs5.67d(7.1)3.79d(1.0),d(7.0)2.14s4.94d(9.6)2.54d(14.8)1.88d(14.7)4.40d(6.7),d(10.9)2.48bs6.27s2.23s6.23q(1.5),t(9.0)1.14s1.24s1.79d(1.5)4.30d(1.1),d(0.8),d(8.4)4.19d(1.0),d(8.5)4.78d(2.7)5.78d(2.8),d(8.9)7.01d(8.9)8.13d(1.3),d(8.4)7.51cm7.61t(1.4),t(7.4)7.48cm7.42cm7.35t(7.3)7.74d(1.2),d(3.3)7.40cm7.49cm C-1C-2C-3C-4C-5C-6C-7C-8C-9C-10C-11C-12C-13C-14C-15C-16C-17C-18C-19C-20C-1’C-2＇C-3′4-OAc,C=OMc10-OAc,C=OC=O,Ph1q-Ph1o-Ph1m-Ph1p-Ph2C=O.Ph3  78.974.945.681.184.335.672.258.5203.675.5113.9141.872.135.743.121.826.814.79.576.6172.773.255.1170.322.5171.2167.2129.2130.1128.9131.9166.9     79.074.945.681.184.435.672.258.6203.675.6113.2142.072.335.743.221.826.914.89.576.6172．773.255.0170.422.6171.3167.0129.1130.2128.7131.9167.0
本发明的优点和积极效果为：本发明制备紫杉醇所用的原料是红豆杉科榧属植物(Torreya)的假种皮，是现用原料红豆杉科红豆杉属植物叶和树皮含量的2倍，且利用的是加工种子后的废弃物假种皮，因而不会破坏植物资源。本发明降低了制备紫杉醇的成本，扩大了其原料的来源，保护了植物资源。

Claims (1)

1、一种制备紫杉醇的方法，包括原料经乙醇提取、硅胶柱层析、高效液相色谱柱分离，其特征在于所用的原料为红豆杉科榧属植物香榧Tnrreya grandis cv．merrillii的假种皮。
CN98110822A 1998-05-07 1998-05-07 一种制备紫杉醇的新方法 Expired - Fee Related CN1060476C (zh)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0521675A1 (en) * 1991-07-05 1993-01-07 E.R. SQUIBB & SONS, INC. Supercritical extraction of taxanes
US5279949A (en) * 1992-12-07 1994-01-18 Board Of Trustees Operating Michigan State University Process for the isolation and purification of taxol and taxanes from Taxus spp
CN1124735A (zh) * 1994-12-17 1996-06-19 浙江省医学科学院 从美丽红豆杉茎叶中提取分离紫杉醇的方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0521675A1 (en) * 1991-07-05 1993-01-07 E.R. SQUIBB & SONS, INC. Supercritical extraction of taxanes
US5279949A (en) * 1992-12-07 1994-01-18 Board Of Trustees Operating Michigan State University Process for the isolation and purification of taxol and taxanes from Taxus spp
CN1124735A (zh) * 1994-12-17 1996-06-19 浙江省医学科学院 从美丽红豆杉茎叶中提取分离紫杉醇的方法

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