- Microbial hydrolysis of 7-xylosyl-10-deacetyltaxol to 10-deacetyltaxol
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Enterobacter sp. CGMCC 2487, a bacterial strain isolated from the soil around a Taxus cuspidata Sieb. et Zucc. plant, was able to remove the xylosyl group from 7-xylosyltaxanes. The xylosidase of this strain was an inducible enzyme. In the bioconversion of 7-xylosyl-10-deacetyltaxol (7-XDT) to 10-deacetyltaxol (10-DT), for the purpose of enhancing the conversion efficiency, the effects of NH4+, oat xylan, temperature, pH value, cell density and substrate concentration on the bioconversion have been systematically investigated. 3.0 mM NH4+, 0.6% oat xylan in the media could enhance the yield of 10-DT; the optimum biocatalytic temperature was 26 °C and optimum pH value was 6.0. The highest conversion rate and yield of 10-DT from 7-XDT reached 92% and 764 mg/L, respectively. In addition, the biocatalytic capacity of the cell cultures remained 66.1% after continuous three batches. These results indicate that converting 7-XDT to 10-DT, a useful intermediate for the semisynthesis of paclitaxel or other taxane-based anticancer drugs by a novel bacterial strain, Enterobacter sp. CGMCC 2487, would be an alternative for the practical application in the future.
- Wang, Kang,Wang, Tingting,Li, Jianhua,Zou, Jianhua,Chen, Yongqin,Dai, Jungui
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p. 250 - 255
(2011/10/12)
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- Process for the Preparation of Synthetic Taxanes
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The present invention relates to a process for the preparation of synthetic taxanes, which protects C(7)-OH with lanthanon compounds. Its advantages are simple process and firm & reliable binding. Moreover, no C(7)-acylated taxanes are produced in the subsequent steps, and hydrolysis of C(2′)-ester groups in acylated products becomes readily controllable. In the process for the preparation of synthetic taxanes, tetrahydrofuran is used in the present invention as a medium for acylation, which not only achieves the same effects as pyridine, but also avoids odor, so as to solve the problem regarding the extremely high requirements for the place of production. The present invention can be used for the preparation of not only semi-synthetic taxane using natural taxanes as raw material, but also full-synthetic taxane.
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Page/Page column 6
(2008/12/09)
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- Synthesis of taxol, analogs and intermediates with variable A-nng side chains
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An efficient protocol for the synthesis of taxol, taxol analogs, and their intermediates is described. The process includes the attachment of the taxol A-ring side chain to baccatin III and for the synthesis of taxol and taxol analogs with variable A-ring side chain structures. A rapid and highly efficient esterification of O-protected isoserine and 3-phenylisoserine acids having N-benzyoloxycarbonyl groups to the C-13 hydroxyl of 7-O-protected baccatin III is followed by a deprotection-acylation sequence to make taxol, calphalomanninne and various analogs, including photoaffinity labeling candidates.
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- Structure-activity relationship study at the 3'-N-position of paclitaxel: synthesis and biological evaluation of 3'-N-acyl-paclitaxel analogues.
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A series of 3'-N-acyl-paclitaxel analogues 1a-v were synthesized and their cytotoxicities in vitro against several human tumor cell lines examined. It has been shown that distinct correlation between activity and N-acyl-substituent. The appropriate size of N-acyl group was indispensable for cytotoxicity, and moreover, the presence of beta-substituted conjugated double and triple bond to N-carbonyl generally resulted in increase of cytotoxicities.
- Roh, Eun Joo,Kim, Deukjoon,Lee, Chong Ock,Choi, Sang Un,Song, Choong Eui
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p. 3145 - 3151
(2007/10/03)
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- A process for the production of taxol
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A process has been developed for production of taxols A,B,C with high yields from 7-xylosyl-10-deacetyl taxol A (taxol analogue A or, xyloside A), 7-xylosyl-10-deacetyl-taxol B (taxol analogue B or xyloside B), 7-xylosyl-10-deacetyl-taxol C (taxol analogue C or xyloside C), which preferably comprises (i) isolating the taxol analogues A,B,C from the stembark of Taxus wallichianaby an improved process devoid of a solvent partitioning step, (ii) treating the isolated taxol analogues A,B,C with periodates in an acid free polar solvent medium to cleave the diol into dialdehyde at ambient temperature (iii) reducing the dialdehyde solution with borohydride in a polar solvent-acetic acid medium at 0-40°C into an acetal, (iv) acidifying the resultant acetal with a mixture of mineral acid-polar solvent at 0-40°C into intermediate product 10-deacetyl taxols A,B,C (v) reacting 10-deacetyl taxols A or B or C with a silane in presence of a base at 20-40°C to protect 2', 7-hydroxyl groups, of 10-deacetyl taxols A,B,C (vi) acetylating the 10-hydroxyl group in situwith an acetylating agent at 10-40°C, (vii) deprotecting the 2', 7-hydroxyl groups with a mixture of mineral acid-polar solvent at 0-10°C (viii) isolating taxols A or B or C by chromatography over silica.
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- Dihalocephalomannine and methods of use therefor
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Provided are antineoplastic derivatives by a process of selective halogenation of side chains of unsaturated taxanes; more particularly, the process involves the use of halogens, particularly bromine, which is easily added to the side chain double bond of cephalomannine, leaving paclitaxel unchanged, and wherein diastereomeric mixtures of 2", 3"-dibromocephalomannine display high activity against: Leukemia cell line HL-60 (TB); Non-Small Cell Lung Cancer line NCI-H522; Colon Cancer cell lines COLO 205 and HT 29; CNS Cancer cell lines SF-539 and SNB-75; Ovarian Cancer Cell line OVCAR-3; Renal Cancer cell line RXF-393; and Breast Cancer cell lines MCF7, MDA-MB-231/ATCC, HS 578T, MDA-MB-435 and MDA-N.
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- Isolation and purification of paclitaxel from organic matter containing paclitaxel, cephalomannine and other related taxanes
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A novel process for extraction, isolation and separation of taxanes, particularly paclitaxel, from natural sources such as bark, needles and twigs from Taxus species, tissue cultures, and fungi is described, wherein the taxanes are separated from the crude extracts by partitioning between polar and nonpolar solvents, precipitation in nonpolar solutions, reacting the mixture by halogenation of unsaturated taxane derivatives, followed by chromatographically separating and crystallizing taxanes from a mixture of polar and nonpolar solvents; more particularly, the process of halogenation of unsaturated side chain taxane derivatives, particularly cephalomannine in presence of paclitaxel, is described, wherein bromine is preferably added to the double bond of unsaturated taxanes leaving paclitaxel unchanged, with paclitaxel being easily separated from the mixture including the less polar halogenated taxane derivatives.
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- Process for isolation of taxol from Taxus sumatrana
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This invention relates to a process for preparing taxol characterized by that taxol is extracted from Taxus sumatrana(Taxaceae) and purified. According to this invention, taxol can be obtained efficiently.
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- Process for separating cephalomannine from taxol using ozone and water-soluble hydrazines or hydrazides
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A process for separating non-oxidizable compounds from a mixture containing at least one oxidizable compound. The mixture is contacted with ozone to oxidize oxidizable compounds to form oxidized compounds which are then converted to water-soluble hydrazones, followed by separation of the hydrazones from the mixture using precipitation, liquid/liquid extraction, chromatography, etc.
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- Process for the preparation of taxol and 10-deacetyltaxol
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Taxol, 10-deacetyltaxol and other taxane derivatives are prepared from naturally occurring taxane-7-xylosides by the oxidative-cleavage of the 7-xyloside moieties.
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