- SEMISYNTHETIC PROCESS FOR THE PREPARATION OF COLCHICINE
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The invention relates to a process for the preparation of colchicine 1 from colchicoside 2 which comprises enzymatic conversion of colchicoside 2 to 3-O- demethylcolchicine 3, wherein the enzyme used is a cellulase. According to another aspect of the invention, 3-O-demethylcolchicine 3 can be converted to colchicine 1 using an alkylating agent. The invention also relates to a process for enriching the colchicine 1 content of extracts from plants belonging to the Colchicaceae family containing colchicine 1, colchicoside 2 and 3 -(9-demethyl colchicine 3, which comprises conversion by means of a colchicoside 2 cellulase to 3-O-demethylcolchicine 3, followed by conversion of 3-O-demethylcolchicine 3 to colchicine 1 using an alkylating agent.
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Page/Page column 11; 12
(2022/01/05)
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- Gram-Scale, Seven-Step Total Synthesis of (-)-Colchicine
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Herein we report a streamlined, gram-scale total synthesis of (-)-colchicine that takes only 7 easy steps, with an overall yield of 27-36%. To warrant the synthetic efficiency and practicality of (-)-colchicine, we tactically utilized a modified version of a powerful Ir-catalyzed amidation reported by Carreira to install the key chiral C-7 acetamido group, Suzuki and biomimetic phenol oxidative coupling, and Banwell-inspired cyclopropane ring cleavage to construct (-)-colchicine precisely and rapidly. Remarkably, a described strategy also can shorten the synthesis of allocolchicinoid to 4 steps.
- Liang, Xiao,Li, Lei,Wei, Kun,Yang, Yu-Rong
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supporting information
p. 2731 - 2735
(2021/04/12)
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- Asymmetric synthesis method of colchicine and allocolchicine
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The invention provides an asymmetric synthesis method of colchicine and allocolchicine, and belongs to the field of chemical synthesis. According to the invention, cheap commercial isovanillin A is used as a raw material, asymmetric allyl amination catalyzed by metal Ir is taken as a key reaction, a cyclization precursor E is obtained through Suzuki coupling reaction with a halide D, allocolchicine F is rapidly synthesized through intramolecular oxidative coupling, and finally, efficient asymmetric synthesis of colchicine I is completed through a bionic cyclopropane ring-opening strategy. Thesynthesis strategy used in the invention is simple and economic, good in operability and short in time consumption, and can meet the requirements of new drug development and large-scale preparation.
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Paragraph 0040; 0043; 0058; 0066-0067
(2020/04/17)
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- Enantioselective total synthesis of (-)-colchicine, (+)-demecolcinone and metacolchicine: Determination of the absolute configurations of the latter two alkaloids
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Here, we describe a concise, enantioselective, and scalable synthesis of (-)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC50 = ～3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
- Chen, Bo,Liu, Xin,Hu, Ya-Jian,Zhang, Dong-Mei,Deng, Lijuan,Lu, Jieyu,Min, Long,Ye, Wen-Cai,Li, Chuang-Chuang
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p. 4961 - 4966
(2017/07/10)
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- Synthesis method of colchicine
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The invention relates to a synthesis method of colchicine. According to the synthesis method of the colchicine, a compound as shown in the specification is used as a raw material, and then efficient intramolecular [5+2] cycloaddition is considered as key reaction; in combination with locating group guided dehydrogenation Hike reaction and Walker reaction, a molecular skeleton structure is rapidly constructed, so that an obtained structural formula, which has the same structure as a natural product, is the colchicine; and a modification research can be carried out on the colchicine favorably, so as to improve the bioactivity and the toxic and side effects of the colchicine.
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- Asymmetric Total Syntheses of Colchicine, β-Lumicolchicine, and Allocolchicinoid N-Acetylcolchinol-O-methyl Ether (NCME)
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A concise and highly enantioselective synthesis of colchicine (>99% ee) in eight steps and 9.3% overall yield, without the need for protecting groups, was developed. A unique Wacker oxidation was used for enabling regioselective construction of the highly oxidized and synthetic challenging tropolone C-ring. Furthermore, asymmetric syntheses of β-lumicolchicine and N-acetylcolchinol-O-methyl ether (NCME) were achieved. Notably, NCME was synthesized from β-lumicolchicine by an unusual decarbonylation and electrocyclic ring-opening cascade reaction.
- Liu, Xin,Hu, Ya-Jian,Chen, Bo,Min, Long,Peng, Xiao-Shui,Zhao, Jing,Li, Shaoping,Wong, Henry N. C.,Li, Chuang-Chuang
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supporting information
p. 4612 - 4615
(2017/09/12)
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- Syntheses and biological evaluation of ring-C modified colchicine analogs
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Ring-C modified alkaloids were synthesized from colchicine using iminonitroso Diels-Alder reactions in a highly regio- and stereoselective fashion. Several analogs exhibited cytotoxic activity similar to that of colchicine itself against PC-3 and MCF-7 cancer cell lines, by serving as prodrugs of colchicine through retro Diels-Alder reactions under the assayed conditions. In vitro microtubule polymerization assays indicated that these modifications affected their interaction with tubulin.
- Yang, Baiyuan,Zhu, Zhiqing C.,Goodson, Holly V.,Miller, Marvin J.
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scheme or table
p. 3831 - 3833
(2010/08/20)
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- Total synthesis of (-)-colchicine by an oxyallyl [4 + 3] cycloaddition
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An enantioselective synthesis of (-)-colchicine, free from isocolchicine, is delineated and features tandem application of the intramolecular Diels-Alder reaction of acetylene-tethered oxazoles and the [4+3] cycloaddition of oxyallyls. This work underscores the synthetic utility of little explored α-alkoxy substituted oxyallyls. (C) 2000 Elsevier Science Ltd.
- Lee, Jae Chol,Cha, Jin Kun
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p. 10175 - 10184
(2007/10/03)
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- Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 2. Colchicine
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The potentiality of interaction of colchicine with β-cyclodextrin (β-CD) was investigated by spectrophotometric and vapour pressure osmometric methods. Differential UV spectrophotometry revealed marked effect of β-CD on the extinction coefficient of colchicine at different wavelengths. The continuous variation method was utilized to elucidate the stoichiometry of molecular interaction via spectrophotometric as well as vapour pressure measurements. Both types of data were in full agreement and revealed the formation of 1:1 complex between colchicine and β-CD. The stability constant of the complex was determined at different temperatures by the vapour pressure osmometric method. The complex was found to undergo partial dissociation with increasing temperature above 25°C and more or less complete dissociation at 60°C. The enthalpy and entropy of interaction were evaluated. The results indicate that the interaction is exothermic and enthalpy-controlled. The colchicine-β-CD complex was prepared; the photochemical stability of the drug, its physical mixture with β-CD and the complex were investigated. The results revealed first-order degradation kinetics. The degradation rate constant as well as the half-life time were computed and the data indicate that inclusion complexation of colchicine with β-CD leads to a marked protection of the drug against photo-degradation.
- Ammar,El-Nahhas
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p. 269 - 272
(2007/10/02)
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- 5,6,7,9-tetrahydro-1,2,3-trimethoxy-9-oxobenzo[alpha]heptalene derivative and pharmaceutical use
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Compounds represented by the formula STR1 wherein R1 and R2 each represent a hydrogen atom or a protective group for a hydroxyl group, or R1 and R2 combine to represent a protective group for hydroxyl groups, and R3 represents CH3 O-- or CH3 NH--. These compounds exhibit a strong effect to inhibit proliferation of cancer cells and are expected to be used as a carcinostatic agent.
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- Synthesis and Tubulin Binding of Novel C-10 Analogues of Colchicine
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A series of novel C-10 derivatives of colchicine have been prepared and evaluated for inhibition of in vitro microtubule assembly and of colchicine binding to tubulin.The C-10 substituent of colchicine was replaced by halogens, alkyl and alkoxy groups, and hydrogen.Many of these compounds are available by nucleophilic substitution of 10-fluoro-10-demethoxycolchicine (9) without concomitant formation of ring contraction products.Compound 9 is prepared by reaction of (diethylamino)sulfur trifluoride with colchicine.Unlike most reactions of colchicine, the colchicine rather than the isocolchicine regioisomer is the predominant product of this reaction.It was found that modification of the C-10 substituent of colchicine had a relatively minor effect on the potency of the colchicinoids.The electronic nature of the substituent had no significant effect on the efficacy of the compound, indicating that hydrogen bonding or polar interactions between the C-10 substituent of colchicinoids and an amino acid in the colchicine binding site on tubulin are not present in the colchicine-tubulin complex.A decrease in activity was observed with increasing length of the alkyl chain bonded to the C-10 position, but potency was less affected when the alkyl groups were positioned in close proximity to the C-10 carbon of the tropone ring.It is concluded that the steric rather than the electronic properties of the C-10 substituent are the predominant determinants of activity in this series.
- Staretz, Marianne E.,Hastie, Susan Bane
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p. 758 - 764
(2007/10/02)
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- 2,10-DIDEMETHYLCOLCHICINE - A NEW ALKALOID FROM MERENDERA ROBUSTA
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The alkaloid complex of Merendera robusta Bge. (family Liliaceae) growing in the Tashkent province of the Uzbek SSR has been investigated.The main alkaloids of this plant are colchicine and colchamine.Eleven tropolone alkaloids and their photochemical isomers have been isolated and identified.A new alkaloid of phenolic nature has been isolated for which the structure of 2,10-didemethylcolchicine has been established.
- Chommadov, B. Ch.,Yusupov, M. K.,Aslanov, Kh. A.
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- THE BIOSYNTHESIS OF THE PHENETHYLISOQUINOLINE ALKALOID, COLCHICINE, FROM CINNAMALDEHYDE AND DIHYDROCINNAMALDEHYDE
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The important phenethylisoquinoline alkaloid, colchicine (10) is shown to derive from cinnamic acid (5) via cinnamaldehyde (6) and dihydrocinnamaldehyde (7); dihydrocinnamic acid (4) may be used by a minor pathway.
- Herbert, Richard B.,Knagg, Eric
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p. 1099 - 1102
(2007/10/02)
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