133524-70-6Relevant articles and documents
Method for synthesizing paclitaxel from cephalomannine (by machine translation)
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Paragraph 0015; 0035-0036; 0041-0042; 0047-0048, (2019/07/29)
The method comprises the following steps: (≥ 9997%) bases as a raw material, N - Butene keys on the side chains of the bases 13 through low-temperature acid hydrolysis; and protecting; and NH (NH-7 ') in the side chains 2, 13 -'. 2 The method has the advantages of mild 7 and 2 controllable reaction conditions, low cost, high yield, high product purity, low impurity content, and suitability for industrial production and market popularization and application 99%. the method comprises the following steps: synthesizing and converting paclitaxel crude product through crystallization, carrying out one-time column chromatography and primary recrystallization purification to obtain paclitaxel. (by machine translation)
Trifluoro isopropyl-substituted taxol derivatives, and applications thereof
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, (2017/07/22)
The invention relates to novel trifluoro isopropyl-substituted taxol derivatives. The trifluoro isopropyl-substituted taxol derivatives are compounds represented by formula I, and isomers, corresponding compounds, or pharmacologically acceptable salts of the compounds, wherein R is used for representing hydrogen atom, or C1-C4 straight-chain paraffins or branched chain paraffins, or C2-C4 straight-chain acyl or branched chain acyl. The invention also provides a preparation method of the trifluoro isopropyl-substituted taxol derivatives, and applications of the trifluoro isopropyl-substituted taxol derivatives in preparing antitumor drugs.
Synthesis of deuterium-labelled paclitaxel and its hydroxyl metabolite
Tian, Lei,Wu, Keying,Tao, Jie,Chen, Liqin
, p. 318 - 323 (2012/02/03)
This paper describes the synthesis of deuterium-labelled paclitaxel and its hydroxyl metabolite. Paclitaxel labelled with 2H was obtained in four steps using the commercially available [2H5]benzoic chloride as the stable l
An N-aroyltransferase of the bahd superfamily has broad aroyl CoA specificity in vitro with analogues of N-dearoylpaclitaxel
Nevarez, Danielle M.,Mengistu, Yemane A.,Nawarathne, Irosha N.,Walker, Kevin D.
experimental part, p. 5994 - 6002 (2009/09/24)
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.
A PROCESS FOR THE PURIFICATION OF 10-DEACETYLBACCATINE III FROM 10-DE ACET YL-2- DEBENZOYL-2-PENTENOYLBACCATINE III
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Page/Page column 6-7, (2008/06/13)
A process for the preparation of 10-deacetyl-7,10-bis- trichloroacetylbaccatine III with HPLC purity higher than 99% and free from 2-debenzoyl-2-pentenoylbaccatine III by purification of 10-deacetyl-7,10-bis- trichloroacetylbaccatineIII followed by alkaline hydrolysis of the protecting groups in position 7 and 10.
Method and compositions for preparing a compound using a benzoylating agent essentially free of ring chlorination
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Page/Page column 4, (2010/10/19)
This invention relates to methods and compositions for preparing compounds using a benzoylating agent essentially free of ring chlorination. In one alternative embodiment, the present invention relates to methods and compositions for preparing taxanes essentially free of ring chlorinated impurities. In another alternative embodiment, the present invention comprises methods of converting taxane amine with a benzoylating agent essentially free of ring chlorination.
Semi-synthesis of taxane intermediates and aziridine analogues and their conversion to paclitaxel and docetaxel
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Page/Page column 10, (2008/06/13)
A process is provided for the semi-synthesis of taxane intermediates and aziridine analogues of cephalomannne and baccatin III intermediates, and the conversion of such intermediates and analogues to paclitaxel and docetaxel.
No auxiliary, no byproduct strategy for water-soluble prodrugs of taxoids: Scope and limitation of O-N intramolecular acyl and acyloxy migration reactions
Skwarczynski, Mariusz,Sohma, Youhei,Noguchi, Mayo,Kimura, Maiko,Hayashi, Yoshio,Hamada, Yoshio,Kimura, Tooru,Kiso, Yoshiaki
, p. 2655 - 2666 (2007/10/03)
Since numerous new taxoids active against multidrug resistant (MDR) tumors have been developed and their poor water-solubility is a very real problem in intravenous administration, we have designed and synthesized a series of novel water-soluble taxoid prodrugs (isotaxoids). These prodrugs, a 2′-O-isoform of taxoids, showed promising results with higher water solubility (0.8-1.1 mg/mL) and proper kinetics for parent drug release by a simple pH-dependent chemical mechanism via O-N intramolecular acyl migration. No additional functional auxiliaries are released during the conversion to parent drugs, which would be an advantage in toxicology and general pharmacology, and the cost for the evaluations of auxiliary units in these fields could be saved in prodrug development. In addition, we demonstrate for the first time the successful application of the O-N intramolecular acyloxy migration reaction in the prodrug design, with the exception of the tert-butyloxycarbonyl group, and that this reaction can be provided with no organic solvent and no side products.
Structure-activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells
Ojima, Iwao,Fumero-Oderda, Cecilia L.,Kuduk, Scott D.,Ma, Zhuping,Kirikae, Fumiko,Kirikae, Teruo
, p. 2867 - 2888 (2007/10/03)
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.
O-N Intramolecular acyl migration strategy in water-soluble prodrugs of taxoids
Skwarczynski, Mariusz,Sohma, Youhei,Kimura, Maiko,Hayashi, Yoshio,Kimura, Tooru,Kiso, Yoshiaki
, p. 4441 - 4444 (2007/10/03)
We synthesized a highly water-soluble canadensol prodrug 6 that formed canadensol 3 by a simple pH-dependent chemical mechanism via the O-N intramolecular acyl migration of the isobutyryl group. This prodrug, a 2′-O-isobutyryl isoform of 3, has no additio
