Taxane diterpenoids from the seeds of Chinese yew Taxus chinensis

The taxoid chinentaxunine has been isolated from the seeds of Chinese yew Taxus chinensis, and its structure determined on the basis of spectral and chemical methods. In addition, the known taxol C, paclitaxel, 10-deacetyl taxol A, 10-deacetyl-7-epitaxol, 10-deacetyl-10-oxo-7-epi-taxol, taxinine M, taxchinin A, 10-deacetyl taxinine B and taxuspine X were also isolated and identified from this source.     

Synthesis and biological evaluation of methoxylated analogs of the newer generation taxoids IDN5109 and IDN5390

Starting from 10-deacetylbaccatin III (7), the 2-debenzoyl-2-m-methoxybenzoyl analogs of the newer generation taxoids IDN5109 (3) and IDN5390 (4) were synthesized. The biological evaluation of these compounds (5 and 6, respectively) showed a general increase of cytotoxicity, as observed in first-generation anticancer taxanes.     

14Beta-hydroxy-10-deacetylbaccatin III as a convenient, alternative substrate for the improved synthesis of methoxylated second-generation taxanes

This article describes a new, convenient, improved synthesis of the 2-debenzoyl-2-m-methoxybenzoyl-7-triethylsilyl-13-oxo-14beta-hydroxybaccatin III 1,14-carbonate, the key intermediate in the synthesis of two new second-generation antitumor taxanes.     

New 14-hydroxy-taxane and 2alpha,20-epoxy-11(15-->1)abeotaxane from the needles of Taxus canadensis

Two new taxanes were isolated from the needles of Taxus canadensis. Their structures were established as 10beta,13alpha-diacetoxytaxa-4(20),11-diene-5alpha,9alpha,14beta-triol (1) and 4alpha,13alpha-diacetoxy-2alpha,20-epoxy-11(15-->1)abeotaxa-11,15-diene-5alpha,7beta,9alpha,10beta-tetraol (2) on the basis of a spectroscopic analysis.     

中国红豆杉枝叶中的紫杉烷二萜

从中国红豆杉(Taxus chinensis)枝叶的乙醇提取物中分离得到8个紫杉烷二萜,通过波谱分析分别确定为：14p羟基巴卡亭Ⅵ(1),巴卡亭Ⅵ(2),巴卡亭Ⅳ(3),1β-去羟基巴卡亭Ⅳ(4),云南红豆杉酯甲(5),2α-去乙酰-2α-苯甲酰基-13α-乙酰基云南紫杉亭(6),5α-羟基-2α,7βp,9α,10β,13α-五乙酰氧基紫杉-4(20),11-二烯(7)和Taxaein(8)。其中化合物1为新化合物,并报道八个化合物在丙酮中测得的核磁共振信号,化合物8的数据属首次报道。     

Two new alkaloidal taxoids from the needles of Taxus canadensis

Two new taxanes with a dimethylamino group on the C-5 side chain were identified for the first time in the needles of the Canadian yew, Taxus canadensis. Their structures were characterized as 7beta,10beta,13alpha-triacetoxy-5alpha-(3'-dimethylamino-3'-phenylpropanoyl)oxy-2alpha-hydroxy-2(3-->20)abeotaxa-4(20),11-dien-9-one (1) and 2alpha,10beta-diacetoxy-9alpha-hydroxy-5alpha-(3'-dimethylamino-3'-phenylpropanoyl)oxy-3,11-cyclotax-4(20)-en-13-one (2).     

Three new taxanes with the 10-alkoxy group from the heartwood of Taxus cuspidata

Three novel taxanes with the 10-alkoxy group were isolated from heartwood of Taxus cuspidata. The structures were identified as 2alpha,14beta-diacetoxy-10beta-ethoxytaxa-11,4(20)-dien-5alpha-ol (1), 2alpha,14beta-diacetoxy-10beta-methoxytaxa-11,4(20)-dien-5alpha-ol (2), and 2alpha-acetoxy-10beta-ethoxytaxa-11,4(20)-diene-5alpha,14beta-diol (3) on the basis of spectroscopic analysis. These are the first taxanes with an alkoxy moiety on the skeleton.     

Improved paclitaxel production in a two-phase suspension culture ofTaxus cuspidata using silicone cubes

Two-phase cultures ofTaxus cuspidata were performed using silicone cubes as a second phase in shake flasks for paclitaxel production. Among various taxanes, paclitaxel was selectively adsorbed on the silicon cubes. When silicone cubes were added to suspension culture ofTaxus cuspidata, paclitaxel production increased about 45 folds. The maximum paclitaxel production was 3.95 mg/L when 10% of silicone cubes were added to the culture at the 7th day from inoculation.     

Two new taxoids from Taxus chinensis

Two new taxoids, 2,20-O-diacetyltaxumairol N (1) and 14beta-hydroxy-10-deacetyl-2-O-debenzoylbacatin III (2), were isolated from the needles and stems of Taxus chinensis. Their structures were determined on the basis of extensive 1D- and 2D-NMR-spectral analysis. Compound 1 showed weak cytotoxicity activity against T-24 (IC50 = 34 microg/ml) and QGY-7701 (IC50 = 22 microg/ml) cancer lines. Compound 2 showed no obvious cytotoxicity activity against T-24 (IC50 > 100 microg/ml) and QGY-7701 (IC50 > 100 microg/ml) cancer lines.     

Two new taxanes from the needles and branches bark of Taxus cuspidata

Two new taxanes were isolated from the MeOH extract of the needles and branches bark of the Japanese yew, Taxus cuspidata. The structures were established as (2alpha,5alpha,7beta,9alpha,10beta,13alpha)-5,10,13,20-tetraacetoxytax-11-ene-2,7,9-triol (1) and (2alpha,5alpha,9alpha,10beta)-2,9,10-triacetoxy-5-[(beta-D-glucopyranosyl)oxy]-3,11-cyclotax-11-en-13-one (2) on the basis of in-depth 1D- and 2D-NMR analyses. Compound 2 is the first example of a transannular taxane glycoside isolated from a natural source.     

南方红豆杉枝叶中6种紫杉烷类化合物含量季节变化

紫杉醇(taxol)是主要来源于红豆杉属植物的一种天然抗肿瘤药物,紫杉烷(taxane)是紫杉醇的代谢前体或支路代谢产物,同样具有开发成为抗肿瘤新药的潜质。本文采用高效液相色谱法研究了紫杉醇(Taxol)、10-去乙酰巴卡亭Ⅲ(10-DAB)、7-木-10-去乙酰紫杉醇(7-xyl-10-DAT)、10-去乙酰紫杉醇(10-DAT)、三尖杉宁碱(CE)和7-表-10-去乙酰紫杉醇(7-epi-10-DAT)6种紫杉烷类化合物在南方红豆杉枝叶中含量的季节变化,结果显示Taxol和10-DAT在8、9月份含量最低,10-DAB和7-xyl-10-DAT在8、9月份含量相对最高,Taxol含量季节变化和10-DAB呈负相关,与CE呈显著正相关。7-xyl-10-DAT含量季节变化和10-DAB、10-DAT分别呈正相关。本文为研究南方红豆杉中紫杉醇及相关紫杉烷的代谢、积累规律提供了依据,不但有助于阐明紫杉醇的生物合成的关键步骤及调控的生理机制,而且对红豆杉资源的深度开发具有指导意义。     

Taxanes with C-5-amino-side chains from the needles of Taxus canadensis

Five taxanes with an amino-side chain on C-5 were identified for the first time in the needles of the Canadian yew, Taxus canadensis. Their structures were characterized as 2alpha,7beta,9alpha,10beta,13-pentaacetoxy-11beta-hydroxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),12-diene (1), 2alpha,9alpha-dihydroxy-10beta,13alpha-diacetoxy-5alpha-(3'-methylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (2), 2alpha17-dihydroxy-9alpha,10beta,13alpha-triacetoxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (3), 2alpha-hydroxy-7beta,9alpha,10beta,13alpha-tetraacetoxy-5alpha-(2'-hydroxy-3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (4), and 9alpha-hydroxy-2alpha,10beta,13alpha-triacetoxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (5) on the basis of 1D-, 2D-NMR spectroscopic data and high-resolution fast atom bombardment MS analyses. Metabolite (1) was isolated from the needles of the Canadian yew for the first time but had previously been detected in the stems of the Japanese yew, whereas taxanes (2-5) are only now reported. Metabolite (3) is the first reported nitrogen-containing taxane with a 17-hydroxyl substitution.     

Synthesis and microtubule binding of fluorescent paclitaxel derivatives

The preparation of two new fluorescent derivatives of paclitaxel in which the fluorophore is bonded to paclitaxel at the C-10 position is reported. Both analogues, 10-deacetyl-10-(m-aminobenzoyl)paclitaxel (1, BTax) and 10-deacetyl-10-[7-(diethylamino) coumarin-3-carbonyl]paclitaxel (2, CTax) retain good activity as promoters of in vitro tubulin assembly. Microtubule binding enhances the emission intensity of both probes.     

Free taxanes and the release of bound compounds having taxane antibody reactivity by xylanase in female,haploid-derived cell suspension cultures ofTaxus brevifolia

Summary Haploid cells derived from the female gametophyte ofTaxus brevifolia produce multinucleate egglike cells that have grown as cell suspensions over a 5-yr period. Two new media are formulated, one without nitrates, to select for haploid cell lines and to enhance free taxane production when cell lines are artificially aged by withholding subculture. The cell suspensions produce bound taxanes that are detectable with anti-taxane monoclonal antibodies on cell surfaces and on particles released into the culture medium. Recovery and detection of bound taxanes are based on a competitive inhibition enzyme immunoassay (CIEIA). Tissues extracted exhaustively with methanol then treated with xylanase release CIEIA-detectable taxanes. Approximately 300% more taxanes were detected in the xylanase-treated tissue culture material versus the control. Wood (winter bark) taken fromT. brevifolia and treated in the same way with xylanase release 20% more taxanes than could be detected in the control.     

Diterpenes and sesquiterpenes from the bark of Taxus yunnanensis

Two taxane-type diterpenes, 10beta-acetoxy-2alpha,5alpha,7beta,9alpha-tetrahydroxytaxa-4(20),11-dien-13-one and 2alpha-acetoxy-9alpha-benzoyloxy-5alpha,7beta,10beta,15-tetrahydroxy-11(15-->1)- abeotaxa-4(20),11-dien-13-one, and two new drimane-type sesquiterpenes, 1beta-acetoxy-7-drimen-11alpha-ol-12,11-lactone and 1beta-acetoxy-11,12-epoxy-6-drimen-8alpha,11alpha-diol, were isolated from the bark of Taxus yunnanensis together with 35 known taxane-type diterpenes, a known drimane-type sesquiterpene and a known flavanone.     

Separation of taxanes from <Emphasis Type="Italic">Taxus canadensis</Emphasis> using dynamic pressurized liquid extraction

An extraction technique, dynamic pressurized liquid extraction (DPLE), was proposed to extract the taxanes; including 10-DAB III, Baccatin III, 9-DHB III and paclitaxel, from powdered Taxus canadensis needles. A dual-solvent approach was adopted in which the impurities were firstly removed by extraction with hexane, and the taxanes were subsequently extracted with an appropriate solvent. The performance of chloroform, dichloromethane, and mixtures of methanol/dichloromethane was compared for use as the taxane-extracting solvent, and it was found that solvents containing a higher proportion of methanol had higher extraction capabilities. The effect of temperature on DPLE extraction of the taxanes was also studied, and it was found that higher extraction efficiencies could be realized with increasing temperature up to a threshold of 90°C. Based on a progressive conversion model, a kinetic equation for the extraction process was proposed. This model successfully confirmed that smaller needle powder particle sizes would result in higher extraction rates, which is consistent with the data obtained by experimentation.     

云南红豆杉紫杉烷2α-O-苯甲酰转运酶基因的克隆及定性

通过RACE技术,克隆了云南红豆杉紫杉烷2α-O-苯甲酰转运酶基因(TyTBT),该酶催化2-去苯甲酰-7,13-二乙酰巴卡亭Ⅲ生成7,13-二乙酰巴卡亭Ⅲ,是紫杉醇合成途径中的关键酶之一.TyTBT基因cDNA全长1481 bp,含有1 320 bp的开放读码框,编码440个氨基酸的多肽,分子量为50 050 Da,等电点为6.17.氨基酸序列比对表明TyTBT同植物酰化酶家族的其它成员有较高的相似性,超过67%,同东北红豆杉和曼地亚红豆杉的紫杉烷2α-O-苯甲酰转运酶氨基酸序列的一致性和相似性达到最高,分别为95%和96%.广泛地比对分析证明这种较高的相似性在红豆杉属的其它酶家族中具有普遍性,进化树分析表明同东北红豆杉和曼地亚红豆杉的紫杉烷2α-O-苯甲酰转运酶(TBT)的相似性高于紫杉醇合成途径中的其它酰化酶.     

Chemical Studies on Taxus canadensis

A series of new taxanes, 1 – 93 , have been isolated, together with 37 known taxoids including Taxol^® (paclitaxel) and cephalomannine, from the Canadian yew, Taxus canadensis (Taxaceae) in the past 30 years. These new taxoids possess various skeletons containing 5/7/6, 6/10/6, 6/5/5/6, 6/8/6, and 6/12 ring systems and six new taxanes with four novel skeletons, i.e., a taxane with a 6/6/8/6 ring system, a taxane with a [3.3.3] propellane skeleton, three taxanes with [3.3.3] [3.4.5] dipropellane sytems, as well as a novel taxane with a unique 5/5/4/6/6/6 hexacyclic skeleton, containing a unique [3.3.2] propellane, were isolated for the first time from natural sources. It should be emphasized that 13‐acetyl‐9‐dihydrobaccatin III, a very useful starting material for the semisynthesis of Taxol^® and Taxotere^®, represents the most abundant taxane in the needles of this yew tree. These findings establish the above mentioned yew tree as significantly different from the remaining species. On the other hand, some chemical modifications on the taxanes isolated from this plant were carried out.     

Two new polyhydroxysteroids from the gorgonian Isis hippuris

Two new polyhydroxysteroids isihippurols A (1) and B (2) were isolated from the MeOH extract of the gorgonian Isis hippuris in addition to nine known steroids namely gorgosterol, 3alpha-acetoxy-24-methyl 11beta,18; 18,20beta; 22,25-triepoxy-5alpha-furostane, hippurin-1, 22-epi-hippuristanol, 22-epi-hippurin-1, 3-acetyl-2-deacetyl-22-epi-hippurin-1, 2-deacetylhippurin-1, 3beta, 7alpha, 11alpha-trihydroxygorgost-5-ene-12beta-acetate and 2-deacetyl-22-epi-hippurin-1. The structures of 1 and 2 have been determined as 1alpha, 3beta, 5alpha, 6beta, 11alpha-pentahydroxygorgosta-12beta-monoacetate and 1alpha, 3beta, 11alpha-trihydroxygorgosta-5alpha, 6alpha-epoxy-12beta-monoacetate respectively by spectral analysis and chemical correlation.     

Inhibitory effect of 13 taxane diterpenoids from Chinese yew (Taxus chinensis var. mairei) on the proliferation of HeLa cervical cancer cells

The inhibitory effect of 13 taxanes isolated from the Chinese yew (Taxus chinensis var. mairei) on the proliferation of human cervical cancer HeLa cells were examined using an MTT assay. Four compounds having a hydrophobic cinnamate side chain showed antiproliferative activity, which may be due to increased cell permeability.