工业色谱法分离制备7-木糖基-10-去乙酰紫杉醇酶解产物10-去乙酰紫杉醇

基于工业色谱法分离制备抗癌药物紫杉醇的半合成前体10-去乙酰紫杉醇(10-DAP)。7-木糖基-10-去乙酰紫杉醇(10-DAXP)在我国特有红豆杉品系(中华红豆杉)枝叶中含量丰富,以其为原料可制备紫杉醇最理想的半合成前体——10-DAP。本研究以部分纯化后的7-木糖基-10-去乙酰紫杉烷为原料,通过β-木糖苷酶水解该粗提物中的主要成分10-DAXP及其两个微量类似物7-木糖基-10-去乙酰三尖杉宁碱(10-DAXC)和7-木糖基-10-去乙酰紫杉醇C(10-DAXP C),脱去其C-7位上的木糖基,水解产物采用大孔吸附树脂吸附,正相快速柱分离和反相制备色谱分离,可获得高纯度的目标物10-DAP,产物纯度为96%,整个工艺的收率大于75%。该方法适合以10-DAXP为原料大规模制备紫杉醇的半合成前体化合物10-DAP,为工业化生产紫杉醇开辟了一条新途径。     

去乙酰毛花苷的流动注射化学发光分析研究

在碱性介质中,去乙酰毛花苷对鲁米诺-KIO4发光体系有明显的抑制作用,且抑制效果与其质量浓度呈良好的线性关系,据此建立了去乙酰毛花苷的流动注射化学发光分析方法。该方法的线性范围为1.0×10-8~1.0×10-5g/mL,检出限为3.1×10-9g/mL,对1.0×10-7g/mL的去乙酰毛花苷进行连续11次平行测定,相对标准偏差为2.3%。可用于相应注射剂分析,并与药典方法进行对照。     

高效液相色谱-串联质谱法同时测定鸡蛋中头孢噻肟及其主要代谢物残留

建立了高效液相色谱-串联质谱(HPLC-MS/MS)法同时测定鸡蛋中头孢噻肟及其代谢物去乙酰头孢噻肟残留量的检测方法.样品经乙腈-水(9∶1, V/V)提取,正己烷除脂,C18固相分散萃取除杂,Agilent Eclipse Plus C18色谱柱(100 mm×2.1 mm, 3.5 μm)分离,以0.2%(V/V)甲酸-乙腈为流动相,进行梯度洗脱,目标物采用电喷雾正离子(ESI+)模式电离,多反应监测(MRM)模式检测,基质匹配标准溶液外标法定量.结果表明,头孢噻肟和去乙酰头孢噻肟分别在1.0~143.0 μg/L和1.0~120.0 μg/L浓度范围内线性关系良好(R.2>0.999).方法检出限(LOD, S/N=3)分别为0.07和0.14 μg/kg,定量限(LOQ, S/N=10)分别为0.23和0.99 μg/kg. 在5.0、50.0和100.0 μg/kg 3个添加水平下,头孢噻肟和去乙酰头孢噻肟的回收率分别为83.1%~103.0%和88.2%~101.0%,相对标准偏差(RSD, n=6)均介于2.0%~6.2%.实际样品测定结果表明,本方法简便、快速、灵敏、准确, 可用于鸡蛋中头孢噻肟及去乙酰头孢噻肟的残留分析检测.     

6α-羟基紫杉醇的合成

以紫杉醇为原料,经过羟基保护、磺酸化、烯化、双羟基化、构型翻转、去除保护基,得到6α-羟基紫杉醇。目标化合物和中间体的结构经1H NMR、MS确证,总收率为3.97%。     

新乡红豆杉中多种紫杉烷类化合物的反相高效液相色谱分析

采用反相高效液相色谱法(RP-HPLC)研究了新乡种植红豆杉树皮中的多种紫杉烷类化合物.结果表明,新乡种植红豆杉树皮中的10-去乙酰巴卡丁Ⅲ、巴卡丁Ⅲ、7-木糖-10-去乙酰基三尖杉宁碱、7-木糖-10-去乙酰基紫杉醇、7-木糖-10-去乙酰基紫杉醇C、10-去乙酰基紫杉醇、三尖杉宁碱和紫杉醇的平均含量(质量分数,n=...     

2-O-乙酰和3-O-乙酰-4,6-苯亚甲基-α-D葡萄糖甲甙的核磁共振鉴别法

本文报告了用同核相关二维核磁共振氢谱和核磁共振碳谱两种核磁共振方法来鉴别氟代去氧六碳糖化合物合成中关键性中间体2-O-乙酰和3-O-乙酰-α-D-4,6-苯亚甲基葡萄糖甲甙的结果。     

去叔丁基杯[8]芳烃乙酸钠对紫杉醇包合作用的研究

采用紫外分光光度法和荧光光谱法研究去叔丁基杯[8]芳烃乙酸钠对紫杉醇的包合和释放过程,考察了二者物质的量之比、温度等因素对包合作用的影响.结果显示去叔丁基杯[8]芳烃乙酸钠在一定条件下与紫杉醇可形成稳定的超分子包合物,包合后水溶性明显提高,且随着去叔丁基杯[8]芳烃乙酸钠/紫杉醇物质的量之比的增加,荧光强度明显增强.去叔丁基杯[8]芳烃乙酸钠今后有望成为紫杉醇类抗肿瘤药物的良好载体.     

反相HPLC法分析红豆杉树皮和树叶中紫杉醇及其类似物含量的研究

建立了红豆杉树皮和树叶中紫杉醇及四种类似物１０－脱乙酰浆果赤霉素Ⅲ（１０－ｄｅａｃｅｔｌｙ－ｂａｃｃａｔｉｎⅢ）浆果赤霉素（Ｂａｃｃａｔｉｎ（Ⅲ），脱乙酰－７－表－紫杉醇（１０ｄｅａｃｅｔｙｌ－７－ｅｐｉ－ｔａｘｏｌ）和Ｃｅｐｈａｌｏａｎｎｉｎｅ）的梯度和等梯度高效液相色谱分析方法。     

常山酮中间体的合成工艺改进

以2-乙酰呋喃为起始原料,经扩环、甲基化、去质子化、亲核加成、缩酮化、Rh/C催化氢化及水解等反应合成了常山酮中间体--1-(3-甲氧基哌啶-2-基)丙酮,总收率40.2%,其结构经¹H NMR和ESI-MS确证。     

新型溴乙酰四胺化合物的合成

以四胺盐酸盐和2-溴乙酰溴为起始原料,在碳酸钾和二氯甲烷/水中通过缩合反应合成了两个新型溴乙酰四胺化合物,其结构经1H NMR和MS表征.     

紫杉醇研究进展

紫杉醇是目前最新的具有很好疗效的抗癌药物, 本文对自紫杉醇发现以来的最新研究进展进行了比较详尽的综述。包括以下几个部分: 1.紫杉醇的发现和历史; 2. 紫杉醇的来源; 3. 紫杉醇的全合成研究; 4. 紫杉醇的生物合成; 5. 通过真菌生产紫杉醇; 6.通过植物细胞培养生产紫杉醇; 7. 紫杉醇化学研究的展望。     

西藏红豆杉中紫杉醇及相关紫杉烷含量的高效液相色谱分析

确立了紫杉醇及５种相关紫杉烷类化合物的反相高效液相色谱分析方法。最佳条件是用ＲｅｓｏｌｖｅｐａｋＣ１８柱,甲醇－水为流动相,紫外２２８ｎｍ检测。对６种化合物在反相柱上的保留机理进行了初步探讨。６种化合物的线性范围为０．１～２．０μｇ,最低检测限为０．１μｇ。     

Studies on taxol biosynthesis. Preparation of 5α-acetoxytaxa-4(20),11-dien-2α,10β-diol derivatives by deoxygenation of a taxadiene tetra-acetate obtained from Japanese yew

The putative metabolite, 5α-acetoxytaxa-4(20),11-dien-2α,10β-diol (7), which is a promising candidate as a biosynthetic pathway triol in taxol biosynthesis, has been prepared by Barton deoxygenation of the C-14-hydroxyl group of a differentially protected derivative of natural 2α,5α,10β-triacetoxy-14β-(2-methyl)-butyryloxytaxa-4(20),11-diene (8), a major taxoid metabolite isolated from Japanese Yew heart wood. The synthetic protocol devised, is amenable for the preparation of isotopically labeled congeners that will be useful to probe further intermediate steps in the biosynthesis of taxol.     

抗癌药物紫杉醇的制备、抗癌机理和应用前景

紫杉醇具有显著的抗癌活性和独特的作用机理,现主要用于治疗晚期乳腺癌和卵巢癌等。紫杉醇分子结构复杂,具有特殊的三环[6+8+6]碳架和桥头双键以及众多的含氧取代基,其全合成引起国内外许多有机化学家的兴趣。本文简述紫杉醇的制备、抗癌机理和不良反应。     

Semi-synthesis of paclitaxel from naturally occurring glycosidic precursors

Paclitaxel, an antitumor drug effective on ovarian and breast carcinomas, is currently being produced both by direct isolation from the bark of Taxus brevifolia and by semi-synthesis from a natural precursor, 10-deacetyl baccatin III. Although other potential precursors such as 10-deacetyl paclitaxel-7-xyloside were known since 1984, their conversion to paclitaxel could not be achieved because of the lack of suitable methodology for hydrolyzing the xylose residue, compatible with the stability of the compound. A method is described here using periodate, followed by phenylhydrazine, to effect deglycosidation of 10-deacetyl paclitaxel-7-xyloside to form 10-deacetyl paclitaxel. In addition, by including an intermediate acetylation step before the reaction with phenylhydrazine, “direct” conversion of this xyloside to paclitaxel itself, is described. Because 10-deacetyl paclitaxel-7-xyloside occurs at >0.1% in the bark of Taxus brevifolia, its successful hydrolytic conversion to paclitaxel represents an extremely important reaction for the enhanced availability of this drug.     

Fluorescent taxoids

Background: Taxol^* is a natural product produced by the Pacific Yew, Taxus brevifolia, that has emerged as a prominent chemotherapeutic agent for the treatment of solid tumors. Taxol's biochemical mode of action has been well studied: it binds to microtubules, stabilizing them and preventing their depolymerization to tubulin subunits. At lower dosage levels, taxol also interferes with the normal dynamics of the tubulin—microtubule equilibrium. This biochemical effect causes taxol's ultimate physiological effect, cell cycle arrest; taxol is thought to block anaphase A of mitosis. Taxol also causes a number of intriguing secondary effects on interphase cells that are poorly understood. We believed that a bio-active fluorescent taxol derivative could be a useful tool in the study of these cellular mechanisms, especially in interphase cells.Results: We have synthesized and characterized a series of stable, fluorescently labeled derivatives of taxol that bind to microtubules and have cytotoxicities similar to that of taxol. Fluorescence microscopy experiments in interphase human foreskin fibroblast (HFF) cells indicate that one of these, a sulforhodamine taxoid, is particularly well suited for optical microscopy. The use of this taxoid in HFF cells revealed a previously undetected localization of taxoids to the nucleolus during interphase.Conclusion: The production of a new fluorescent derivative of taxol provides a useful tool, enabling cellular biologists to study taxol's mechanism of action. It is hoped that this material will prove particularly useful for the study of taxol's effects upon interphase cells.     

Separation of 7-xylosyl-10-deacetyl paclitaxel and 10-deacetylbaccatin III from the remainder extracts free of paclitaxel using macroporous resins

The separation and enrichment of 10-deacetylbaccatin III (10-DAB III) and 7-xylosyl-10-deacetyl paclitaxel were studied on seven macroporous resins with special structures. The performance of 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III on macroporous resins including AB-8, ADS-17, ADS-21, ADS-31, ADS-8, H1020 and NKA-II was compared according to their adsorption and desorption properties. AB-8 provided a much higher adsorption capacity for 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III than other resins, and its adsorption data fitted well to the Langmuir and Freundlich isotherm. According to the adsorption and desorption capacities and the adsorption isotherms, AB-8 demonstrated a remarkable capability for the preparative separation of 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III from the remainder extracts free of paclitaxel. In order to optimize parameters of separation, dynamic adsorption and desorption experiments were carried out on the columns packed with AB-8 resin. The optimal conditions were: the processing volume 15 BV; concentrations of 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III in feed solution 0.0657 mg/mL and 0.1494 mg/mL; flow rate 1 mL/min; temperature 35 degrees C. The gradient elution program was as follows: 30% ethanol for 3 BV, then 80% of ethanol for 6 BV, flow rate 1 mL/min. After the AB-8 resin treatment, the contents of 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III in the product had increased from 0.053% and 0.2% to 3.34% and 1.69%, which were 62.43-fold and 8.54-fold of those in the untreated extracts, respectively, and the recoveries of 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III were 85.85% and 52.78%. The performance achieved good separation and higher recovery of 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III from remainder extracts free of paclitaxel by using AB-8 resin. It is a fast and effective method for the separation and enrichment of 7-xylosyl-10-deacetyl paclitaxel and 10-DAB III.     

Ring-closing metathesis in the synthesis of BC ring-systems of taxol

BC ring-systems of taxol with different or no protecting group for the C1,C2-diol moiety have been efficiently synthesized. The eight-membered B ring is formed by a ring-closing metathesis reaction (RCM) between the C10 and C11 carbon atoms. The influence of the 1,2-diol protecting group on the RCM reaction has been studied in detail.     

紫杉醇的分离纯化及其检测

综述了紫杉醇的分离纯化及其检测方法。