- 7 - epi - Baccatin III derivative as well as preparation method and application thereof
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The present invention provides 7-epi-baccatin III derivatives shown as a general formula 1 or a pharmaceutically acceptable salt thereof, and a preparation method, a pharmaceutical composition and use thereof. The 7-epi-baccatin III derivatives shown as the general formula 1 or the pharmaceutically acceptable salt thereof can be used for treatment of cancer, especially prostate cancer (prostate carcinoma), non-small cell lung cancer, breast cancer, colon cancer, liver cancer, ovarian cancer, and the like.
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Paragraph 0084-0086
(2021/01/24)
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- Synthesis and biological evaluation of novel larotaxel analogues
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Taxoids are a class of successful drugs and have been successfully used in chemotherapy for a variety of cancer types. However, despite the hope and promises that these taxoids have engendered, their utility is hampered by some clinic limitations. Extensive structure-activity relationship (SAR) studies of toxoids have been performed in many different laboratories. Whereas, SAR studies that based on the new-generation toxoid, larotaxel, have not been reported yet. In view of the advantages in preclinical and clinical data of larotaxel over former toxoids, new taxoids that strategicly modified at the C3’/C3′-N and C2 positions of larotaxel were designed, semi-synthesized, and examined for their potency and efficacy in vitro. As a result, it has been shown that the majority of these larotaxel analogues are exceptionally potent against both drug-sensitive tumor cells and tumor cells with drug resistance arising from P-glycoprotein over expression. Further in vivo antitumor efficacies investigations revealed A2 might be a potent antitumor drug candidate for further preclinical evaluation.
- Ren, Sumei,Wang, Yujie,Wang, Junfei,Gao, Dingding,Zhang, Minmin,Ding, Ning,Li, Yingxia
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p. 692 - 710
(2018/07/29)
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- Facile Synthesis of 7-epi-Taxane and Its Derivatives and Preliminary Evaluation of Anticancer Activity
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7-epi-Taxane has been achieved efficiently in gram scale from natural taxane via inversion of the 7-hydroxyl group simply using Ag2O as catalyst and DMF as solvent. The catalyst could be quantitatively recovered by filtration without loss of catalytic activity. This condition is also applicable to the direct epimerization of taxane derivatives (e.g., docetaxel and paclitaxel) to 7-epi-taxane derivatives (e.g., 7-epi-docetaxel and 7-epi-paclitaxel). Furthermore, 33 ester derivatives of 7-epi-taxane with different amino acid moieties at the position of C-13 were successfully synthesized via esterification without protecting C-7-OH. Bioassay results revealed that compounds 13 and 18 have good selectivity against prostatic cancer cell line DU145, with IC50value as low as 15.9 nmol/L for 18.
- Li, Zhao,Feng, Jia,Zou, Kun,Yang, Zhuo,Zhang, Yong,Xu, Zhijian,Li, Bo,Shi, Jiye,Li, Yiming,Zhu, Weiliang,Chen, Kaixian
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p. 1165 - 1176
(2016/11/25)
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- Method for preparing 7-epi-taxane compounds
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The invention relates to a method for preparing 7-epi-taxane compounds from 7-beta-hydroxy taxane compounds. The method comprises the step of converting 7-beta-hydroxy taxane compounds into 7-epi-taxane compounds in the solvent S under the existence of a
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Paragraph 0068-0070
(2017/03/14)
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- Biological degradation of taxol by action of cultured cells on 7-acetyltaxol-2″-yl glucoside
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Biodegradation pathways of taxol in cultured cells of Synechocystis sp. PCC 6803, Synechococcus sp. PCC 7942, Marchantia polymorpha, Nicotiana tabacum, and Glycine max were investigated using a water-soluble taxol derivative, 7-ace-tyltaxol-2″-yl glucoside, as the substrate. Although cyanobacteria, Synechocystis sp. PCC 6803 and Synechococcus sp. PCC 7942, and a lower plant, M. polymorpha, catalyzed the epimerization at 7-position of taxol skeleton, no epimerization occurred with higher plants, N. tabacum and G. max. On the other hand, Synechocystis sp. PCC 6803, Synechococcus sp. PCC 7942, M. polymorpha, and N. tabacum catalyzed hydrolysis at 13-position of taxol to give baccatin III and 10-deacetyl baccatin III. Both cyanobacteria cells also deacetylated 7-epi-baccatin III at its 10-position. M. polymorpha and G. max deacetylated at 10-position of taxol. Copyright
- Shimoda, Kei,Mikuni, Katsuhiko,Nakajima, Kiyoshi,Hamada, Hatsuyuki,Hamada, Hiroki
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p. 362 - 363
(2008/09/20)
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- Process for the preparation of 4, 10 beta- diacetoxy-2 alpha-benzoyloxy-5 beta, 20-epoxy-1, 13 alpha-dihydroxy-9-oxo-19-norcyclopropa [g] tax-11-ene
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There is disclosed a process for the preparation of 4 -acetoxy-2α-benzoyloxy-5β,20-epoxy-1,13α-dihydroxy-9 -oxo-19-norcyclopropa[g] tax-11-ene from 4-acetoxy-2α-benzoyloxy-5β,20-epoxy-1,13α-dihydroxy-9-oxo-7β-(trifluoromethyl sulfonyloxy) tax-11-ene by re
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- Process for selective derivatization of taxanes
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A process is described for converting the C(7) hydroxy group of a 10-acyloxy-7-hydroxytaxane to an acetal or ketal, the process comprising treating the 10-acyloxy-7-hydroxytaxane with a ketalizing agent in the presence of an acid catalyst to form a C(7) ketalized taxane of the formula or wherein either X31 or X32 represents the 10-acyloxy-7-hydroxytaxane moiety and the other of X31 and X32 as well as X33 and X34 are independently hydrocarbyl, substituted hydrocarbyl or heteroaryl moieties. Taxanes having a ketalized C(7) hydroxy group are also described.
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- Process for selective derivatization of taxanes
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A process for the acylation of a C(10) hydroxy group of a taxane comprises treating the taxane with an acylating agent selected from dicarbonates, thiodicarbonates, and isocyanates in a reaction mixture containing less than one equivalent of a base for each equivalent of taxane to form a C(10) acylated taxane.
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- Process for selective derivatization of taxanes
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A process for the silylation of a C(10) hydroxy group of a taxane comprises treating the taxane with a silylamide or a bissilylamide to form a C(10) silylated taxane.
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- Acid catalyzed conversions of taxoids
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Treatment of 10-deacetylbaccatin-III and baccatin-III with dilute HCl affords 10-deacetylbaccatin-V and baccatin-V, respectively. 10-Deacetylbaccatin-V is also obtained when 10-deacetylbaccatin-III is treated with ZnCl2 or ZnBr2 in MeOH. These two Lewis acids convert baccatin-III to 10-deacetylbaccatin-III as well 10-deacetylbaccatin-V. BF3.OEt2 in CH2Cl2 opens the oxetane ring of 7,13-diacetylbaccatin-III to form two regioisomeric products while BBr3 in the same solvent leads to the contraction of its A-ring along with the oxetane cleavage. CF3COOH contracts the A-ring of 7-acetylbaccatin-III and 7,13-diacetylbaccatin-III.
- Das, Biswanath,Srinivas,Ravindranath,Ramesh,Venkataiah,Das, Ratna
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p. 667 - 670
(2007/10/03)
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- Selective protection of the C(7) and C(10) hydroxyl groups in 10- deacetyl baccatin III
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New protocols for the selective protection of the C(7) and C(10) hydroxyl groups of 10-deacetyl baccatin III are described, leading to more efficient semisyntheses of taxol and taxol analogs. The C(10) hydroxyl group of 10-DAB can be highly selectively acylated or silylated, and subsequent selective protection of the C(7) hydroxyl group then becomes straightforward.
- Holton, Robert A.,Zhang, Zhuming,Clarke, Paul A.,Nadizadeh, Hossain,Procter, D. John
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p. 2883 - 2886
(2007/10/03)
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- Synthesis of carbon-14 labeled Taxolo (paclitaxel)
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Reductive cleavage of the C13 side chain of Taxolo (1, paclitaxel) followed by regioselective silylation gave 7-triethylsilylbaccatin III (4). 3-O-Triethylsilylation of 5 and subsequent reaction with benzoyl chloride-C7-14C gave azetidinone 7. Coupling of 4 and 7 followed by deprotection gave 1.26 g of Taxol-N3'14C (11) having a specific activity of 26.5 mCi/mmol and a radiochemical purity of 95%.
- Walker,Swigor,Kant,Schroeder
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p. 973 - 980
(2007/10/02)
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- THE CHEMISTRY OF TAXANES: REACTIONS OF TAXOL AND BACCATIN DERIVATIVES WITH LEWIS ACIDS IN APROTIC AND PROTIC MEDIA
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Several Lewis acids were shown to cleanyl open the oxetane ring of taxol and baccatin derivatives.The reaction is shown to proceed via anchimeric assistance by the C-4 acetate group.Several minor products, including a novel derivative possessing a bridged C-ring, were also isolated.A mechanistric rationale is provides for all compounds formed.When taxol derivatives were treated with Lewis acids in methanol, ester cleavage reactions were observed.We provide conditions that are selective for C-10 acetate cleavage and for C-13 side-chain methanolysis.
- Chen, Shu-Hui,Huang, Stella,Wei, Jianmei,Farina, Vittorio
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p. 2805 - 2828
(2007/10/02)
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- A facile synthesis of 7,10-dideoxy taxol and 7-epi-10-deoxy taxol
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7,10-Dideoxy taxol 2 was prepared from baccatin III in 4 steps via the Barton deoxygenation reaction. Similarly, 7-epi-10-deoxy taxol 3 was prepared in one step from 7-epi taxol in high yield. The key reaction was the tributyltin hydride-mediated directed reduction of the C10 acetate.
- Chen,Wei,Vyas,Doyle,Farina
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p. 6845 - 6848
(2007/10/02)
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- Anitleukemic Alkaloids from Taxus wallichiana Zucc.
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A new antileukemic taxane alkaloid, cephalomannine (1a), has been isolated from leaves, stems, and roots of Taxus wallichiana Zucc.Cephalomannine is closely related to taxol (1b), a previously characterized antileukemic alkaloid, which also occurs in T. wallichiana but in lesser amounts than cephalomannine.The new alkaloid and its hydrolysis products were characterized by nuclear magnetic resonance, mass spetroscopy, and X-ray crystallography; taxol and two cytotoxic taxane congeners were also identified.
- Miller, Roger W.,Powell, Richard G.,Smith, Cecil R.
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p. 1469 - 1474
(2007/10/02)
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