液-质联用研究红豆杉提取物中紫杉烷类化合物

建立了一套利用反相高效液相色谱和大气压化学电离质谱联用技术分析红豆杉提取物中微量紫杉烷类化合物的方法。通过研究已知的10种紫杉烷类化合物的保留时间、质谱特征，初步建立了一个紫杉烷类化合物的数据库，利用这些数据可快速鉴定红豆杉提取物中已知的紫杉烷类化合物，并能够对未知化合物做一定程度的结构分析。这种研究方法同样对其他天然产物特别是微量成分结构分析具有指导作用。     

Taxane Diterpenoids from Taiwanese Yew Taxus sumatrana

Thirty seven taxanes were characterized from the leaves and twigs of Taiwanese yew (Taxus sumatrana, Taxaceae). Four of these metabolites are new and designated as sumataxins A–D ( 1 – 4 ). Compound 1 possesses an 11(15→1),11(10→9)‐di‐abeo‐taxane skeleton with an unusual spiro‐connected 2,2‐dimethyl‐1,3‐dioxolane ring at C(4), whereas compound 2 has a rare β‐OH orientation at C(13) of taxane diterpene ester. In addition, sumataxin C ( 3 ) is formulated as an 11(15→1)‐abeo‐taxane with a 4,5‐acetonide ring skeleton. Compound 4 is the first metabolite with a 4,20‐epoxy‐taxane structure. The structures of all the taxanes were established by spectroscopic methods. All compounds were evaluated for anti‐HSV‐1 and PBMC activities. Compound 9 exhibited significant enhancement of cell proliferation on peripheral blood mononuclear cells.     

Novel taxane diterpenes from Taxus sumatrana with the first C-21 taxane ester

Phytochemical investigation of the taxane diterpenes content of an acetone extract of the leaves and twigs of Taxus sumatrana (Taxaceae) has resulted in the isolation of five new taxane diterpenes esters, tasumatrols H-L (1-5) together with 13 known taxanes (11-23). Compound 5 is the first 21-carbon taxane ester to be isolated from a natural source. The structures of these taxanes as well as their derivatives were established on the basis of spectral analyses, especially MS as well as 1-and 2D NMR. Compounds 2 and 4 showed significant activity against human liver carcinoma (Hepa59T/VGH), human large cell carcinoma of the lungs (NCI), human cervical epitheloid carcinoma (Hela), human colon adenocarcinoma (DLD-1) and human medulloblastoma (Med) cell lines.     

Toward an efficient synthesis of taxane analogs by dienyne ring-closing metathesis

An efficient tandem ring-closing dienyne metathesis of dienynes derived from cyclohex-2-enone affords the [5.3.1] carbon framework characteristic of taxanes in a single-step process. Further stereoselective functionalizations of the resulting [5.3.1] carbon framework lead to an advanced intermediate in a novel synthetic strategy for taxane analogs.     

Synthesis and stereochemistry of a saturated tricyclic taxane model

The construction through an A-ring annulation strategy of a fully B-ring methylated saturated tricyclic taxane model and the demonstration of its preference for trans BC ring junction stereochemistry are described.     

A New Taxane Diterpenoid from the Seeds of Taxus yunnanensis

Plant from the genus of Taxus are a rich source of biologically active diterpennodsbelonging to the unique structural family of taxoids'. Although more than 300 taxoidswere isolated from yew tree', new taxoids still were isolated. In our continuing studieson the yew tree, we have previously isolated several new taxoids from seeds of theChinese yew, Taxus chinensiS var mairei. T yunnanensiS, and Japanese yew, TCuspidata'-'. Further investigation on the extract of the seeds of T yunnanensis …     

Application of SPE for the HPLC analysis of taxanes fromTaxus cell cultures

Summary Solid phase extraction (SPE) methods are studied for the sample pretreatment for HPLC analysis ofTaxus cell suspension cultures. Various types of SPE materials were tested for the extraction of both the taxane standards and samples of various origin. Comparison between the different cartridges and the different elution solvents are made in terms of extraction recovery and sample clean-up. Selective elution of the taxanes is achieved by a gradient elution scheme.     

Matrix-assisted laser desorption/ionization mass spectrometry of taxanes

Taxanes are biologically active compounds that have been extensively used in pharmacology for their powerful anticancer properties. High specificity and low level sensitivity for analysis of these compounds have been obtained with reversed-phase high-pressure liquid chromatography/mass spectrometry (RP-HPLC/MS), but the number of applications of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for low molecular weight analytes is rapidly growing. A new MALDI-MS approach for the rapid screening of a variety of taxanes and a tandem mass spectrometric (MS/MS) analysis of the most important and diagnostic taxane fragmentation pathways are proposed. A solid-phase extraction method followed by preliminary quantification is also reported.     

Taxanes from the leaves of <Emphasis Type="Italic">Taxus cuspidata</Emphasis>

A new taxane, 13-oxobaccatin III (2), and five known taxanes, 10-deacetyl-13-oxobaccatin III (1), baccatin III (3), 7-epi-10-deacetyltaxol (4), 19-debenzoyl-19-acetyltaxinine M (5), and 5a-decinnamoyltaxagifine (6), were isolated from the leaves of the Japanese yew, Taxus cuspidate. Their structures were established on the basis of the analysis of their spectral data.     

Synthetic studies on taxane diterpenes X-ray structure of a key intermediate

Michael condensation of the dienone (3) with the vinyllactone (19) leads to the compound (20). Attempts to construct the B ring of the taxane skeleton by direct cyclization of (20) are reported . The stereochemistry of (20) is established by X-ray structure determination.     

Quantification of taxanes in a leaf and twig extract from Taxus baccata L. using 13C NMR spectroscopy

In the course of our ongoing work on the chemical characterization of Taxus baccata L. growing wild in Corsica, we have developed and validated a method for direct quantification of taxane derivatives by ¹³C NMR using 10‐deacetylbaccatin III as reference compound and 1,6‐hexanediol as internal standard. We have observed good accuracy (relative errors between 0.3% and 3.5%), linearity (R² = 0.999) and precision (reproducibility 8.5 mg ± 1.1%) of the measurements. The experimental procedure was applied to the quantification of six identified taxanes in a fraction of chromatography of a methanol extract of T. baccata leaves. This method can be applied to other compounds bearing the taxane skeleton. Copyright © 2013 John Wiley & Sons, Ltd.     

Tasumatrols P – T,Five New Taxoids from Taxus sumatrana

The phytochemical investigation of the more polar fractions from the leaves and twigs of Taxus sumatrana (Taxaceae) afforded five new taxane diterpene esters, tasumatrols P–T ( 1 – 5 ) possessing an 11(15→1),11(10→9)‐diabeotaxane skeleton. Compounds 1, 4 , and 5 contain an α‐hydroxy group at C(14), while 3 has no OH group at either C(13) or C(14). Compound 2 is a natural 4,5‐acetonide derivative, while 4 has an unusual spiro‐connected 2‐hydroxy‐2‐phenyl‐1,3‐dioxolane ring. Ten known taxoids, were also isolated in the course of the chromatographic fractionation. Five additional new O‐acetyl derivatives 3a, 4a, 4b, 5a , and 5b were prepared from the taxanes 3 – 5 . The structures of all new compounds were established on the basis of their spectroscopic analyses. Compound 1 showed mild cytotoxic activity against human Hela and Daoy tumor cells.     

Nature as a crystal engineer: Trapping hydronium cations inside crystalline lattices – three heretofore unknown hydronium cations,two of which are geometrical isomers

Examination of the structural data between 2000 and the last release of the Cambridge Structural Database (2006) revealed the existence of three new hydronium cations not previously known, plus a few other ones whose stereochemistry was already documented, even if the exact geometrical details were somewhat different from those previously described.     

Novel taxoids from the Chinese yew Taxus yunnanensis

Six new taxoids, taxuyunnanines W (1), X (2), Y (3), Z (5), 10-deacetyl-10-(β-glucopyranosyl)-yunnanxane (8), and 7-(β-xylosyl)-N-methyl-taxol C (10), as well as taxuchin B (4) and yunnanxane (7), have been isolated from the bark of Taxus yunnanensis. Compounds 1 and 2 were characterized as 11(15→1)-abeo taxoids containing an orthoester group, which have not been reported from any Taxus plants to date; isolates 3 and 5 are the examples of taxanes having a tetrahydronfuran ring, being reported only for the second time; and 8 is the first natural 6/8/6 skeletal type taxane glucosidic form. This is also the first report of a co-occurrence of xylosidation and N-methylation in a taxane (10). Compound 4 is the only known chlorine-containing taxane found in nature thus far, and is being reported from this plant for the first time. The structures were determined by spectroscopic and chemical means including 1D and 2D NMR spectra.     

Pharmacokinetic measurements of IDN 5390 using electrospray ionization tandem mass spectrometry: structure characterization and quantification in dog plasma

In this report, electrospray ionization tandem mass spectrometry (ESI-MS/MS) for a pharmacokinetic study of IDN 5390, a novel C-seco taxane derivative, which is under preclinical evaluation, has been investigated. Our results showed that IDN 5390 and other taxanes including paclitaxel and IDN 5109 could ionize well in not only positive-, but also in negative-ion mode. Under collision-induced dissociation (CID) conditions, these compounds could fragment into similar M- (molecular), T- (taxane ring) and S- (side chain) series ions. In positive-ion ESI, the formation of both T- and S-series ions involved the breaking of the C-13 ester bond. In negative-ion ESI, however, while the formation mechanism of S-series ions remained the same, the breaking of the C-1' carboxylic ester bond resulted in T-series ions. At optimum collision energy (CE) values, M-, T- and S-series ions of IDN 5390 in both positive- and negative-ion ESI-MS/MS spectra had good intensity. This phenomenon makes both positive- and negative-ion ESI-MS/MS good methods for IDN 5390 metabolite structural characterization, i.e. to reveal the location of modification groups in IDN 5390 metabolites versus IDN 5390 either on the side chain or the taxane ring. A liquid chromatography (LC)/ESI-MS/MS method using the multiple-reaction monitoring (MRM) technique was thereafter developed to quantify IDN 5390 in dog plasma using paclitaxel as internal standard. The method was validated using a concentration range between 5 and 1000 ng/mL and had a limit of detection of 1 ng/mL. The inter-day %CV (%coefficient of variation) of the calibration standards ranged between 4.36 and 9.64%, the intra-day %CV of the calibration standards between 0.61 and 13.44%, and the mean % accuracy of the quality control samples at the low, middle and high end of the concentration curves were 12.5, 6.8 and 9.6%, respectively.     

Permanganate oxidation of 1,5,9-trienes: stereoselective synthesis of tetrahydrofuran-containing fragments

Permanganate oxidation of farnesoate esters 12a-d afforded perhydro-2,2'-bifuranyl compounds 16a-d, with control of relative stereochemistry at four new stereocenters. Subsequent oxidative cleavage of 16a-d then provided tetrahydrofuran-containing fragments 17a-d, one of them 17b possessing the same relative stereochemistry present in the C13-C21 portion of the polyether antibiotic semduramycin (1). Control of the absolute stereochemistry was achieved through the use of the Oppolzer sultam chiral auxiliary. The requisite starting trienes were prepared stereoselectively in just three steps from geranyl chloride or neryl chloride, providing a short and versatile route to polyether fragments.     

Hyosgerin, a new optically active coumarinolignan, from the seeds of Hyoscyamus niger

Hyosgerin, a new optically active coumarinolignan, has been isolated and characterized along with three other coumarinolignans, venkatasin, cleomiscosin A and cleomiscosin B, from the seeds of Hyoscyamus niger L. The structure was determined on the basis of spectroscopic analysis and chemical conversion. The optical properties and absolute stereochemistry of these coumarinolignans have also been studied and discussed.     

Kitungolides A, B, and C, new diterpenes from a soft coral of a new genus

Three novel compounds, designated kitungolides A (1), B (2), and C (3), were isolated from a soft coral of a new genus collected at Kitungamwe, Kenya. The three new compounds are of a unique heterotricyclic skeleton. The structures and relative stereochemistry of the compounds were elucidated by interpretation of MS, COSY, HMQC, HMBC, and NOESY experiments. [structure: see text]     

由D-Erythorbic Acid合成新的多官能团C4手性筑块

手性C4筑块是合成许多天然产物 Leukotrienes, Pyrrolizidine alkaloids及前列腺素A2等的重要合成子[1～3]. 然而到目前为止, 手性C4筑块只有从少数几种手性源如酒石酸, L-苏糖, D-赤藓糖等中才能得到[2～7]. 我们在以D-erythorbic acid为原料合成新型手性配体的过程中[8～10], 发现了一种简便获得选择性保护的多官能团手性C4筑块(化合物4, 5)的新途径(Scheme 1).     

Struktur und stereochemie eines sesquiterpen-esters und dreier sesquiterpen-alkaloide von Celastrus paniculatus Willd

A new sesquiterpene ester (Malkangunin) and three sesquiterpene alkaloids (Celapanin, Celapanigin, Celapagin) were isolated from Celastrus paniculatus Willd. The complete structure and stereochemistry of Malkangunin, a sesquiterpene tetra-ol of the β-dihydroagarofurane type two of whose hydroxyls being esterified with acetic and benzoic acids, is discussed. The alkaloids described here are derived from a new sesquiterpene tetra-ol (Celapanol) which is alternately esterified with acetic, benzoic, nicotinic and β-furoic acids.