ABSTRACT
Echinopines A (1) and B (2), novel sesquiterpenoids with an unprecedented rearranged skeleton named echinopane, were isolated from the roots of Echinops spinosus. The structures were elucidated by extensive spectroscopic analysis. The relative configuration of 1 was assigned by a combination of NOESY correlations and a simulation analysis. A plausible biosynthetic pathway for echinopane was discussed.
Subject(s)
Echinops Plant/chemistry , Plants, Medicinal/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Drug Screening Assays, Antitumor , Female , Humans , Molecular Structure , Sesquiterpenes/pharmacologyABSTRACT
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).
Subject(s)
Alkaloids/chemistry , Alkaloids/isolation & purification , Taxoids/chemistry , Taxoids/isolation & purification , Taxus/chemistry , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
A detailed NMR study and full assignments of the (1)H- and (13)C-NMR spectral data for a novel enolate taxane isolated from Taxus canadensis needles is described. The structures of two stable conformers were established using a combination of 1D and 2D NMR techniques including (1)H, (1)H-COSY, gs-HMQC, gs-HMBC, NOESY and T-ROESY. Ab initio quantum mechanical calculations were performed on the B3LYP/6-31G* level of basis set to assist the NMR findings.
Subject(s)
Magnetic Resonance Spectroscopy/methods , Taxoids/chemistry , Carbon Isotopes , Crystallography, X-Ray , Magnetic Resonance Spectroscopy/standards , Models, Molecular , Molecular Conformation , Protons , Reference Standards , StereoisomerismABSTRACT
A 3,11-cyclotaxane (1), a new epoxytaxane (2), an abeo-taxane (3), and 26 known taxanes were isolated in rooted cuttings of the Canadian yew (Taxus canadensis) for the first time. Their chemical structures were characterized as 1 beta,2 alpha,9 alpha-trihydroxy-10 beta-acetoxy-5 alpha-cinnamoyloxy-3,11-cyclotaxa-4(20)-en-13-one (1), 2 alpha,9 alpha,10 beta-triacetoxy-11,12-epoxy-20-hydroxytaxa-4-en-13-one (2), and 7 beta,9 alpha,10 beta,13 alpha-tetraacetoxy-11(15-->1)abeo-taxa-4(20),11-diene-5 alpha,15-diol (3). Metabolite 2 is a new taxane, metabolite 1 has been reported previously in the needles of Taxus baccata, and metabolite 3 was previously discovered as a biotransformation product but is now reported as a natural product for the first time.
Subject(s)
Bridged-Ring Compounds/isolation & purification , Plants, Medicinal/chemistry , Taxoids/isolation & purification , Taxus/chemistry , Bridged-Ring Compounds/chemistry , Canada , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Stereoisomerism , Taxoids/chemistryABSTRACT
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.
Subject(s)
Taxoids/chemistry , Taxus/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Spectrometry, Mass, Fast Atom Bombardment , Taxoids/isolation & purificationABSTRACT
Five new taxanes, 5alpha,9alpha,10beta,13alpha-tetraacetoxy-14beta-O-(beta-d-glucopyranosyl)taxa-4(20),11-diene (1), 1beta,2alpha,9alpha,10beta-tetrahydroxy-5alpha-cinnamoyoxytaxa-4(20),11-dien-13-one (2), 2alpha,9alpha,10beta-trihydroxy-5alpha-cinnamoyoxytaxa-4(20),11-dien-13-one (3), 9alpha-acetoxy-2alpha,10beta-dihydroxy-5alpha-cinnamoyoxytaxa-4(20),11-dien-13-one (4), and 2alpha,10beta-diacetoxy-1beta,9alpha-dihydroxy-5alpha-cinnamoyoxy-3,11-cyclotaxa-4(20)-dien-13-one (5), have been identified in a Taxus baccata yew grown in Israel from seeds imported from the United States. We have also characterized 40 previously known taxanes from this plant material. The structures of the new taxanes (1-5) were rigorously established with 1D and 2D NMR data and confirmed by high-resolution FAB-mass spectrometry.
Subject(s)
Bridged-Ring Compounds/isolation & purification , Plants, Medicinal/chemistry , Taxoids/isolation & purification , Taxus/chemistry , Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/pharmacology , Israel , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Spectrometry, Mass, Fast Atom Bombardment , Stereoisomerism , Taxoids/chemistry , Taxoids/pharmacologyABSTRACT
The first three examples of taxane-derived [3.3.3][3.4.5] di-propellanes isolated from the needles of a yew tree are reported. They differ in their acetylation pattern and their biogenesis from a putative taxane precursor is proposed.
Subject(s)
Taxoids/chemistry , Taxus/chemistry , Models, Molecular , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
Seven minor taxane derivatives were isolated for the first time from the needles of Taxus canadensis. Four of these natural taxanes are O-glycosylated (1-4), with 4 being the only reported taxane with a glucose on ring C, and two have a dimethylamino-C-5 side chain (5 and 6). An unusual double bond at C-5(6) has been identified in taxane 7.
Subject(s)
Bridged-Ring Compounds/isolation & purification , Plants, Medicinal/chemistry , Taxoids , Taxus/chemistry , Bridged-Ring Compounds/chemistry , Canada , Chromatography, High Pressure Liquid , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Ten new taxanes were isolated from the methanol extract of the needles of the Canadian yew, Taxus canadensis. On the basis of their spectral analysis, their structures were established as 9alpha-hydroxy-2alpha,7alpha,10beta-triacetoxy-5alpha-cinnamoyloxy-3,11-cyclotaxa-4(20)-en-13-one (1), 9alpha,10beta-diacetoxy-5alpha-cinnamoyloxy-3,11-cyclotaxa-4(20)-en-13-one (2), 9alpha,20-dihydroxy-2alpha,10beta,13alpha-triacetoxytaxa-4(5),11(12)-diene (3), 2alpha,9alpha,10beta-triacetoxy-20-cinnamoyloxy-11,12-epoxytaxa-4-en-13-one (4), 9alpha-hydroxy-2alpha,10beta,13alpha-triacetoxy-5alpha-(3'-methylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (5), 2alpha,10beta-diacetoxy-5alpha,9alpha-dihydroxytaxa-4(20),11-dien-13-one (6), 2alpha,9alpha-diacetoxy-5alpha,10beta-dihydroxytaxa-4(20),11-dien-13-one (7), 5alpha,9alpha-dihydroxy-2alpha,10beta,13alpha-triacetoxytaxa-4(20),11-diene (8), 5alpha,10beta-dihydroxy-2alpha,9alpha,13alpha-triacetoxytaxa-4(20),11-diene (9), and 7beta,11beta-dihydroxy-2alpha,9alpha,10beta,13-tetraacetoxy-5alpha-cinnamoyloxytaxa-4(20),12-diene (10). Taxane 1 is the first example of a 3,11-cyclotaxane with a 7-epi-alpha-oxygenated group. Taxane 4 is the first taxane with a C-11,12-epoxide ring as well as a C-4(5)-endo-double bond. Taxanes with a 12(13) double bond as in 10 instead of the usual 11(12) double bond have been found so far only in the needles, stem, and seeds of the Japanese yew.
Subject(s)
Bridged-Ring Compounds/isolation & purification , Plants, Medicinal/chemistry , Taxoids , Taxus/chemistry , Bridged-Ring Compounds/chemistry , Canada , Chromatography, High Pressure Liquid , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The first example of a propellane isolated from the needles of a yew is reported; the biogenesis from a putative taxane precursor is proposed.
Subject(s)
Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/isolation & purification , Taxoids , Taxus/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Plant Leaves/chemistry , Spectrometry, Mass, Fast Atom Bombardment , StereoisomerismABSTRACT
A 7beta-O-glycosylated docetaxel analogue was semi-synthesized from 9-dihydro-13-acetylbaccatin III, the most abundant taxane isolated from the needles of Taxus canadensis. It was shown to be more bioactive than paclitaxel according to the tubulin assay. It had a reduced potency in the MCF7 cell line cytotoxicity assay compared to paclitaxel, but it demonstrated better activity against the drug resistant cell line MCF7-ADR. In addition, the presence of one sugar moiety on C-7 doubled the water solubility versus that of paclitaxel.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/pharmacology , Paclitaxel/analogs & derivatives , Paclitaxel/chemical synthesis , Paclitaxel/pharmacology , Taxoids , Animals , Antibiotics, Antineoplastic/pharmacology , Brain Chemistry/drug effects , Breast Neoplasms/drug therapy , Cattle , Docetaxel , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Female , Glycosylation , Humans , In Vitro Techniques , Indicators and Reagents , Tubulin/biosynthesis , Tumor Cells, CulturedABSTRACT
Seven new taxanes were isolated from the needles of the Canadian yew: unusual functional groups, positions and/or stereochemical features are described. Their chemical structures were rigorously characterized by detailed high resolution NMR analyses and confirmed by high resolution Fast Atom Bombardment Mass Spectrometry. Unlike paclitaxel and taxuspine D, these taxanes had no effect on tubulin assembly.
Subject(s)
Bridged-Ring Compounds/chemistry , Paclitaxel/analogs & derivatives , Taxoids , Taxus/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Bridged-Ring Compounds/isolation & purification , Nuclear Magnetic Resonance, Biomolecular , Paclitaxel/pharmacology , Plant Leaves/chemistry , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
Reduction of 5 alpha-hydroxy-7 beta,9 alpha,10 beta-triacetoxy-4(20), 11(12)-taxadien-13-one 1 with activated zinc in glacial acetic acid led to rearranged products, including compounds with double bonds at C3-C4, C10-C11 or with an epoxide at C11-C12. Molecular modeling studies suggested that addition of a side chain at C-20 or C-5 of the taxanes with a C3-C4 double bond might lead to bioactivity. Semi-syntheses and results of bioactivities are discussed.
