Baccatin VI

The dynamic variation of several important taxane content in post-harvest Taxus chinensis clippings.[Pubmed:16864429]

J Asian Nat Prod Res. 2006 Apr-May;8(3):229-39.

The dynamic variations of several important taxanes, taxol, baccatin III (B-III), 1-acety-5,7,10-deacetyl-baccatin I (DAB-I) and Baccatin VI (B-VI), were investigated in post-harvest clippings of Taxus chinensis. The clippings were preserved over 20 days at two different temperatures (4 degrees C and room temperature), or by cuttage in the light and in the dark, or promptly dried. The accumulation of taxol in needles of the clippings was found increase in the initial stages of the stored period and then decreased gradually. The maximum accumulation of taxol occurred in the case of cold storing (4 degrees C) at day 3, doubling the data on the day when the biomass was harvested. In contrast, in the cases of cold storage and cuttage the contents of the other three taxanes showed a sharp decrease at the beginning and then an increase from 3 to 6 days, and subsequently a drop until day 20. The similar variation of taxane contents was not found in the needles of immediately dried clippings as well as in the stem samples of clippings. These results indicated that the content variation of taxol and related taxanes of post-harvest clippings was related to the manner of preservation, timing and plant tissue. Moreover, the mechanism of the fluctuation of the taxane contents in post-harvest clippings is discussed, in particular taxol biosynthesis in response to mechanical wounding of harvest.

[LC-ESI-MS metabolic profiling analysis of taxanes from the extracts of Taxus chinensis cell cultures].[Pubmed:16268509]

Yao Xue Xue Bao. 2005 Aug;40(8):734-9.

AIM: To develop a rapid analytical method for small amount biological samples of taxanes by using liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS) in small amount biological samples. METHODS: A solution containing five given taxane constituents and the extract from cell cultures of Taxus chinensis were analysed separately. According to the performance of the given taxanes in ESI-MS/MS, run parameters of the mass spectrometer were optimized. Positive and negative electrospray modes were employed to simultaneously scan the cell cultures sample, and the full ion chromatogram and the molecular weight of individual peak were obtained. The qualitative analysis of taxanes was achieved by comparison of the retention time and molecular weight with those of the reference substances or was based on the interpretation of the MS/MS spectra of the analytes and the knowledge of the concerning genetic backgrounds of taxanes published in literatures. RESULTS: The taxanes with several acetyl substituents tended to produce ammonium adduct ions peak, while multi-hydroxy taxanes were subject to give protonized molecular ion peaks in positive ion ESI-MS. Thirteen taxanes in cell samples were assigned. Eight compounds of them were identified to be 1 -acetyl-5, 7, 10-deacetyl-baccatin I (DAB-I, 1) , baccatin III (B-III, 3), Baccatin VI (B-VI, 8), taxol (9), yunnanxane (10 ), taxuyunnanine C (Tc, 11), sinenxane B (12), sinenxane C (13), separately. For the other five constituents, character of taxane and the number of substituents were deduced. CONCLUSION: The results confirm the feasibility of characterizing taxanes in biological samples by LC-ESI-MS analysis. The analytical methodology provided a rapid, conventional and reliable tool to study metabolic profiling of taxanes for structural elucidation in taxol biosynthesis.

Production of biologically active taxoids by a callus culture of Taxus cuspidata.[Pubmed:14738387]

J Nat Prod. 2004 Jan;67(1):58-63.

Ten known taxoids, paclitaxel, 7-epi-taxol, taxol C, Baccatin VI, taxayuntin C, taxuyunnanine C and its analogues (2-5), and yunnanxane (6), and an abietane, taxamairin A, were produced in the callus culture of Taxus cuspidata cultivated on a modified Gamborg's B5 medium in the presence of 0.5 mg/L NAA. After stimulation with 100 microM methyl jasmonate, five more taxoids, cephalomannine, 1beta-dehydroxyBaccatin VI, taxinine NN-11 (1), baccatin I, and 2alpha-acetoxytaxusin, and one more abietane, taxamairin C, were found in addition to the above-mentioned compounds. It was also observed that the content of the products increased over three times. Taxinine NN-11 (1) is a new taxane whose structure was assigned as 5alpha,13alpha-diacetoxy-9alpha-cinnamoyloxy-4(20),11-taxadien-10beta-ol by analysis of its spectral data. Taxinine NN-11 (1) exhibited significant MDR reversal activity toward 2780 AD tumor cells. The results of primary screening based on 39 human cancer cell lines suggest that 1 also belongs to a new mechanistic class. Efficient production of 1 was investigated using the callus culture of T. cuspidata.

Microbial transformation of baccatin VI and 1beta-hydroxy baccatin I by Aspergillus niger.[Pubmed:14643354]

Bioorg Med Chem Lett. 2003 Dec 15;13(24):4493-6.

The biotransformation of Baccatin VI (1) and 1beta-hydroxybaccatin I (2) with the filamentous fungus Aspergillus niger produced four new taxane diterpenoids taxumairol S(1) (3), taxumairol T(1) (4) and taxumairol S (5), taxumairol T (6), respectively. 1beta-DehydroxyBaccatin VI (7) remained unreacted under the same condition.

Anti-inflammatory and antinociceptive activity of taxoids and lignans from the heartwood of Taxus baccata L.[Pubmed:14611890]

J Ethnopharmacol. 2003 Dec;89(2-3):265-70.

Four taxoids (taxusin, Baccatin VI, baccatin III and 1beta-hydroxybaccatin I) and five lignans (lariciresinol, taxiresinol, 3'-demethylisolariciresinol-9'-hydroxyisopropylether, isolariciresinol and 3-demethylisolariciresinol) were isolated from the heartwood of Taxus baccata L. (Taxaceae) growing in Turkey through chromatographic techniques. In vivo anti-inflammatory and antinociceptive activity of these compounds were investigated. All the compounds were shown to possess significant antinociceptive activity against p-benzoquinone-induced abdominal contractions, while only lignan derivatives significantly inhibited carrageenan-induced hind paw edema in mice.

Synthesis and Biological Evaluation of 1-Deoxypaclitaxel Analogues.[Pubmed:11674269]

J Org Chem. 1999 Mar 19;64(6):1814-1822.

The naturally occurring taxoid Baccatin VI has been converted to various 1-deoxypaclitaxel derivatives by selective deacylation followed by attachment of the C-13 side chain. The bioactivities of the resulting analogues were determined in both tubulin polymerization and cytotoxicity assays, and several analogues with activity comparable to that of paclitaxel were discovered. It thus appears that the 1-hydroxyl group is not necessary for the activity of paclitaxel.

Taxoids from the needles of the Canadian yew.[Pubmed:10872214]

Phytochemistry. 2000 May;54(2):221-30.

Systematic characterization of the taxoids in the needles of Taxus canadensis led to the discovery of seven taxanes along with three known congeners. Their structures were rigorously established by spectroscopic methods as 15-benzoyl-10-deacetyl-2-debenzoyl-10-dehydro-abeo-baccat in III; 15-benzoyl-2-debenzoyl-7, 9-dideacetyl-abeo-Baccatin VI; N-acetyl-N-debenzoyltaxol; 7,9,13-trideacetylBaccatin VI; 10-deacetyl-10-glycolylbaccatin IV; 1 beta-hydroxy-10-deacetyl-10-glycolylbaccatin I; and 7-deacetyltaxuspine L. These taxanes, specific to the Canadian yew, were co-isolated with taxacustin, taxagifine and 2-deacetyl-7,10-diacetyl-5-deaminoacyl taxine A previously found in Taxus cuspidata, baccata, and yunnanensis, respectively.

Isolation of labeled 9-dihydrobaccatin III and related taxoids from cell cultures of taxuscell cultures of taxus canadensis elicited with m.[Pubmed:10543900]

J Nat Prod. 1999 Oct;62(10):1395-8.

Cell suspension cultures of Taxus canadensis rapidly produced paclitaxel (1) and other taxoids in response to elicitation with methyl jasmonate. Three of these taxoids, of potential value in the synthesis of taxoid analogues, have been isolated from cell cultures of Taxus canadensis and identified as 13-acetyl-9-dihydrobaccatin III (2), Baccatin VI (3), and 9-dihydrobaccatin III (4). Of these metabolites, 9-dihydrobaccatin III (4) has not been isolated from any Taxus species, whereas 13-acetyl-9-dihydrobaccatin III (2) and Baccatin VI (3) have been isolated from a number of natural sources. 2D NMR techniques, mass spectrometry, and partial synthesis were used to rigorously elucidate the structure and stereochemistry of these natural products.

The kinetics of taxoid accumulation in cell suspension cultures of Taxus following elicitation with methyl jasmonate.[Pubmed:10099517]

Biotechnol Bioeng. 1999 Jan 5;62(1):97-105.

Cell suspension cultures of Taxus canadensis and Taxus cuspidata rapidly produced paclitaxel (Taxol) and other taxoids in response to elicitation with methyl jasmonate. By optimizing the concentration of the elicitor, and the timing of elicitation, we have achieved the most rapid accumulation of paclitaxel in a plant cell culture, yet reported. The greatest accumulation of paclitaxel occurred when methyl jasmonate was added to cultures at a final concentration of 200 microM on day 7 of the culture cycle. The concentration of paclitaxel increased in the extracellular (cell-free) medium to 117 mg/day within 5 days following elicitation, equivalent to a rate of 23.4 mg/L per day. Paclitaxel was only one of many taxoids whose concentrations increased significantly in response to elicitation. Despite the rapid accumulation and high concentration of paclitaxel, its concentration never exceeded 20% of the total taxoids produced in the elicited culture. Two other taxoids, 13-acetyl-9-dihydrobaccatin III and Baccatin VI, accounted for 39% to 62% of the total taxoids in elicited cultures. The accumulation of baccatin III did not parallel the pattern of accumulation for paclitaxel. Baccatin III continued to accumulate until the end of the culture cycle, at which point most of the cells in the culture were dead, implying a possible role as a degradation product of taxoid biosynthesis, rather than as a precursor.

[Isolation and identification of two new taxane diterpenes from Taxus chinensis (Pilger)Rehd].[Pubmed:1442040]

Yao Xue Xue Bao. 1992;27(4):268-72.

Two new taxane diterpenes were isolated from the stem barks of Taxus chinensis grown in Sichuan province of China. Their structures were elucidated by spectral analysis and chemical evidence as 1-hydroxy-7,9-dideacetyl baccatin I(1) and 7,9-dideacetyl Baccatin VI(3).

[Studies on the taxane diterpenes of the heartwood from Taxus mairei].[Pubmed:2618716]

Yao Xue Xue Bao. 1989;24(9):673-7.

A new taxane diterpene and three known taxane diterpenes were isolated from the heartwood of Taxus mairei grown in Fujian province of China and identified as 1-dehydroxy-Baccatin VI, Baccatin VI, 1-dehydroxybaccatin IV, and taxinne J on the basis of spectral data.