- Synthesis of docetaxel and butitaxel analogues through kinetic resolution of racemic β-lactams with 7-O-triethylsilylbaccatin III
-
(Chemical Equation Presented) The kinetic resolution of racemic cis-4-phenyl- and cis-4-tert-butyl-3-hydroxy-β-lactam derivatives with 7-O-triethylsilylbaccatin III yielded paclitaxel and butitaxel analogues with high diastereoselectivity. The results demonstrated that the tert-butyldimethylsilyl protecting group at the C3-hydroxy group of the β-lactams provided optimum kinetic resolution in comparison with the sterically less demanding triethylsilyl group and the larger triisopropylsilyl group. In addition, it was found that the C4 β-lactam substituents also influenced diastereoselectivity. The C4 tert-butyl-β-lactams provided better diastereoselectivity than the corresponding C4 phenyl β-lactams.
- Ge, Haibo,Spletstoser, Jared T.,Yang, Yan,Kayser, Margaret,Georg, Gunda I.
-
-
Read Online
- Synthesis of Taxol and Docetaxel by Using 10-Deacetyl-7-xylosyltaxanes
-
A mixture of taxols was prepared from 10-deacetyl-7-xylosyltaxanes by three-step reactions: redox, acetylation, and deacetylation. The mixture was separated by column chromatography on silica gel to afford Taxol, Taxol B (Cephalomannine) and Taxol C. The mixture of Taxol B and Taxol C was converted to Docetaxel by Schwartz's reagent. The structures of Taxol and Docetaxel were characterized by HPLC, 1H-NMR, 13C-NMR and MS. This synthetic process has expanded the source of biomass for the chemical semi-synthesis of Taxol and Docetaxel, reduced the production costs, and increased the biomass resource of taxanes.
- Xue, Baoyu,Zhao, Junhong,Fan, Yange,Chen, Shipeng,Li, Wenfeng,Chen, Jin,Li, Zheng,Wang, Hongxing,Kong, Hongjun
-
-
- Novel crystalline forms of anticancer compound CX1409 and preparation method and application of novel crystalline forms of anticancer compound CX1409
-
The invention relates to the field of compounds, in particular to two novel crystalline forms of an anticancer compound CX1409. A crystalline form A of the anticancer compound CX1409 is determined byusing a powder X-ray diffraction method, wherein characteristic diffraction peaks are shown at 4.3 degree, 8.7 degree, 11.0 degree, 12.5 degree, 13.0 degree, 14.1 degree, 15.4 degree, 17.4 degree, 18.4 degree, 19.6 degree, 20.1 degree, 20.8 degree, 21.7 degree, 27.0 degree, 29.0 degree, 30.6 degree and 31.4 degree in an X-ray powder diffraction spectrum expressed by a diffraction angle of 2 theta+/-0.3 degree; a crystalline form B of the anticancer compound CX1409 is determined by using the powder X-ray diffraction method, wherein characteristic diffraction peaks are shown at 4.9 degree, 5.4degree, 5.8 degree, 6.4 degree, 8.0 degree, 9.4 degree and 12.9 degree in an X-ray powder diffraction spectrum expressed by a diffraction angle of 2 theta +/-0.3 degree. The above two crystalline forms are not reported, outlines of the two crystalline forms are clear, and the two crystalline forms can be perfectly reproduced; besides, the two crystalline forms have the advantages of being good instability of preparation and high in yield and purity, can be applied to anti-tumor drugs, and have wide application prospects.
- -
-
Paragraph 0054-0055; 0058
(2018/04/01)
-
- Anticancer compound CX1409 dihydrate and DMSO solvate of the new crystal and its preparation method and application (by machine translation)
-
The invention relates to the field of compound, in particular to anti-cancer compounds CX1409 of the dihydrate and DMSO solvate of the two new crystalline form, wherein the anticancer compound CX1409 dihydrate crystalline forms of powder X-ray diffraction for C assay measuring, in order to 2 θ ± 0.3 ° diffraction of said X-ray powder diffraction spectrum in the 5.0 °, 5 . 8°, 10 . 4°, 12 . 8°, 13 . 6°, 15 . 2°, 18 . 6°, 20 . 0°, 20 . 7°, 21 . 6°, 22 . 1° and 22.8 ° for display at the feature diffraction peak. Anticancer compound CX1409 of DMSO solvate crystalline forms of powder X-ray diffraction for D assay measuring, in order to 2 θ ± 0.3 ° diffraction of said X-ray powder diffraction spectrum in the 8.1 °, 8 . 6°, 11 . 1°, 11 . 4°, 12 . 4°, 13 . 0°, 13 . 8°, 14 . 2°, 14 . 8°, 15 . 3°, 15 . 8°, 17 . 2°, 18 . 0°, 18 . 2°, 19 . 7°, 20 . 0° and 22.3 ° for display at the feature diffraction peak. The above two kinds of crystalline form has not been reported, the contours thereof are clear, and can be perfectly reproducing, and has good stability, high yield, purity is high, can be used as the use of the antineoplastic, it has broad application prospects. (by machine translation)
- -
-
Paragraph 0075; 0076; 0079
(2018/03/25)
-
- NOVEL AMINO ACID MOLECULE AND USES THEREOF
-
There is provided novel amino acid molecules and processes for their preparation. There is also provided novel amino acid molecules and their use in processes for preparing the compounds that are useful for the synthesis of paclitaxel, and docetaxel, the anticancer drug.
- -
-
Page/Page column 35-37
(2011/11/12)
-
- An N-aroyltransferase of the bahd superfamily has broad aroyl CoA specificity in vitro with analogues of N-dearoylpaclitaxel
-
The native N-debenzoyl-2'-deoxypaclitaxel:N-benzoyltransferase (NDTBT), from Taxus plants, transfers a benzoyl group from the corresponding CoA thioester to the amino group of the β -phenylalanine side chain of N-debenzoyl-2'-deoxypaclitaxel, which is purportedly on the paclitaxel (Taxol) biosynthetic pathway. To elucidate the substrate specificity of NDTBT overexpressed in Escherichia coli, the purified enzyme was incubated with semisynthetically derived N-debenzoyltaxoid substrates and aroyl CoA donors (benzoyl; ortho-, meta-, and para-substituted benzoyls; various heterole carbonyls; alkanoyls; and butenoyl), which were obtained from commercial sources or synthesized via a mixed anhydride method. Several unnatural N-aroyl-N-debenzoyl-2'-deoxypaclitaxel analogues were biocatalytically assembled with catalytic efficiencies (V max/Km) ranging between 0.15 and 1.74 nmol.min -1.mM -1. In addition, several N-acyl-N-debenzoylpaclitaxel variants werebiosynthesized when N-debenzoylpaclitaxel and N-de(tert-butoxycar-bonyl )docetaxel (i.e., 10-deacetyl-N-debenzoylpaclitaxel) were used as substrates. The relative velocity (v rel) for NDTBT with the lattertwo N-debenzoyl taxane substrates ranged between '1percent and 200pe rcent for the array of aroyl CoAs compared to benzoyl CoA. Interestingly, NDTBT transferred hexanoyl, acetyl, and butyryl more rapidly than butenoyl or benzoyl from the CoA donor to taxanes with isoserinoyl side chains, whereas N-debenzoyl-2'-deoxypaclitaxel was more rapidly converted toits N-benzoyl derivative than to its N-alkanoyl or N-butenoyl congeners . Biocatalytic N-acyl transfer of novel acyl groups to the amino functional group of N-debenzoylpaclitaxel and its 2'-deoxy precursor reveal thesurprisingly indiscriminate specificity of this transferase. This featu re of NDTBT potentially provides a tool for alternative biocatalytic N-aroylation/ alkanoylation to construct next generation taxanes or other novel bioactive diterpene compounds.
- Nevarez, Danielle M.,Mengistu, Yemane A.,Nawarathne, Irosha N.,Walker, Kevin D.
-
experimental part
p. 5994 - 6002
(2009/09/24)
-
- Structure-activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells
-
A series of new taxoids modified at the C-3′, C-3′N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mφ) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mφ-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mφ. Positions C-3′ and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3′N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN Mφ and the cytotoxicity against Mφ-like cells.
- Ojima, Iwao,Fumero-Oderda, Cecilia L.,Kuduk, Scott D.,Ma, Zhuping,Kirikae, Fumiko,Kirikae, Teruo
-
p. 2867 - 2888
(2007/10/03)
-
- Synthesis of taxol, analogs and intermediates with variable A-nng side chains
-
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.
- -
-
Page 8-9, 17
(2010/01/31)
-
- A facile N-debenzoylation of paclitaxel: Conversion of paclitaxel to docetaxel
-
An efficient and regioselective method for the N-debenzoylation of paclitaxel has been developed, and has been applied to the conversion of paclitaxel to 10-acetyldocetaxel and to docetaxel.
- Jagtap,Kingston
-
p. 189 - 192
(2007/10/03)
-