152044-53-6

Basic information

• Product Name: (-)-EPOTHILONE A
• Synonyms: 4,17-Dioxabicyclo14.1.0heptadecane-5,9-dione, 7,11-dihydroxy-8,8,10,12-tetramethyl-3-(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl-, (1S,3S,7S,10R,11S,12S,16R)-;Epothilone-S;(1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12-tetramethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione;Epothile;4,17-Dioxabicyclo[14.1.0]heptadecane-5,9-dione,7,11-dihydroxy-8,8,10,12-tetraMethyl-3- [(1E)-1-Methy;Ixabepilone Impurity 5 (Epothilone A);(1S,3S,7S,10R,11S,12S,16R,E)-7,11-dihydroxy-8,8,10,12-tetramethyl-3-(1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione;(1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12-tetramethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione Epothilone A
• CAS NO: 152044-53-6
• Molecular Formula: C₂₆H₃₉NO₆S
• Molecular Weight: 493.66
• Product Categories: Chiral Reagents;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 152044-53-6.mol

Chemical Properties

• Melting Point: 95℃
• Boiling Point: 683.317 °C at 760 mmHg
• Flash Point: 367.057 °C
• Appearance: /
• Density: 1.143
• Vapor Pressure: 1.31E-19mmHg at 25°C
• Refractive Index: 1.531
• Storage Temp.: ?20°C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly)
• PKA: 13.57±0.70(Predicted)
• CAS DataBase Reference: (-)-EPOTHILONE A(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-EPOTHILONE A(152044-53-6)
• EPA Substance Registry System: (-)-EPOTHILONE A(152044-53-6)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 152044-53-6(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
(-)-Epothilone A is used as an antineoplastic agent for its ability to inhibit microtubule dynamics, leading to cell cycle arrest at the G2/M transition and inducing apoptosis. (-)-EPOTHILONE A has shown resistance to overexpression of β-tubulin and P-glycoprotein, making it a promising candidate for treating various types of cancer, including human bladder carcinoma.
Used in Drug Development:
(-)-Epothilone A is used as a microtubule inhibitor in the development of novel anticancer drugs. Its mechanism of action involves stabilizing microtubule formation at the taxol binding site, which results in cytotoxicity. This property has led to the investigation of (-)-Epothilone A in clinical trials as a potential antitumor agent, offering a new avenue for cancer treatment.
Used in Pharmaceutical Research:
(-)-Epothilone A is used as a research tool in the pharmaceutical industry for studying the effects of microtubule stabilization on cancer cell growth and the development of drug resistance. Its unique structure and mechanism of action provide valuable insights into the design of new antineoplastic agents and the understanding of cancer cell biology.

Biological Activity

epothilone a (epo a) is a naturally occurring microtubule-stabilizing macrolide that was first isolated from the myxobacterium sorangium cellulosum. the ic50 value of epothilone a in hct-116 cell line is 4.4 nm [1].it has been found that the skov-3 human ovarian cancer cells were susceptible to epothilone a with ic50 value of 20.4 ± 1.4 nm [2]. the antiproliferative capacity of epothilone a in skov-3 cell line (measured as ic50 after 72 h continuous treatment) was six times greater than that of ptx’s. besides, epothilone a induced time coursedependent apoptosis and necrosis [2].

references

[1] regueiro-ren a1, borzilleri rm, zheng x, kim sh, johnson ja, fairchild cr, lee fy, long bh, vite gd. synthesis and biological activity of novel epothilone aziridines. org lett. 2001 aug 23;3(17):2693-6.[2] rogalska a1, marczak a, gajek a, szwed m, ?liwińska a, drzewoski j, jó?wiak z. induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone a and b. toxicol in vitro. 2013 feb;27(1):239-49.

InChI:InChI=1/C26H39NO6S/c1-14-8-7-9-19-21(32-19)11-20(15(2)10-18-13-34-17(4)27-18)33-23(29)12-22(28)26(5,6)25(31)16(3)24(14)30/h10,13-14,16,19-22,24,28,30H,7-9,11-12H2,1-6H3/b15-10+/t14-,16+,19+,20-,21-,22-,24-/m0/s1

Upstream product

• 186692-73-9 desoxyepothilone A 
• 342607-36-7 (7S)-(tert-butyl-dimethyl-silanyloxy)-(11S)-hydroxy-8,8,(10R,12S)-tetramethyl-(3S)-[1-methyl-(2E)-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione 
• 479485-03-5 (1S,3S,7S,10R,11S,12S,16R)-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-11-hydroxy-7-(4-methoxybenzyloxy)-8,8,10,12-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione 
• 479485-07-9 (4S,7R,8S,16S)-8-hydroxy-4-(4-methoxybenzyloxy)-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-1-oxacyclohexadec-13-en-2,6-dione 
• 479485-01-3 (Z)-(4S,7R,8S,9S,16S)-8-(tert-Butyl-dimethyl-silanyloxy)-4-(4-methoxy-benzyloxy)-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione 
• 187283-49-4 (Z)-(4S,7R,8S,9S,16S)-4-(tert-Butyl-dimethyl-silanyloxy)-8-hydroxy-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione 
• 461044-22-4 (4S,5S)-4-Hydroxy-5-methyl-tetrahydro-pyran-2-one 
• 473251-43-3 (4S,5S)-5-Methyl-tetrahydro-pyran-2,4-diol 
• 461044-23-5 (3S,4R,5S)-3-Allyl-4-hydroxy-5-methyl-tetrahydro-pyran-2-one 
• 461044-25-7 (S)-2-((1R,2S)-1,3-Dihydroxy-2-methyl-propyl)-pent-4-enoic acid methyl ester 
• 461044-29-1 (4S,5S)-2-(4-Methoxy-phenyl)-5-methyl-4-((S)-1-methyl-but-3-enyl)-[1,3]dioxane 
• 461044-31-5 (2R,3S,4S)-3-(4-Methoxy-benzyloxy)-2,4-dimethyl-hept-6-enal 
• 461044-30-4 (2S,3S,4S)-3-(4-Methoxy-benzyloxy)-2,4-dimethyl-hept-6-en-1-ol 
• 461044-27-9 (R)-2-[(4R,5S)-2-(4-Methoxy-phenyl)-5-methyl-[1,3]dioxan-4-yl]-pent-4-en-1-ol 

Downstream Products

• 186692-73-9 desoxyepothilone A 
• 298200-29-0 [4S-[4R*,7S*,8R*,9R*,13R*,14R*,16R*(E)]]-14-Azido-5,5,7,9-tetramethyl-16-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-13-[(4-nitrobenzoyl)oxy]-4,8-bis [(triethylsilyl)oxy]-1-oxacyclohexadecane-2,6-dione 
• 201049-37-8 epothilone E 
• 201049-37-8 epothilone E 

Relevant articles and documents

Total synthesis of epothilone A.

[reaction: see text]Epothilones A (1) and B (2) are potent antitumor natural products with a Taxol-like mechanism of action. A total synthesis of epothilone A (1) is reported, which utilized chiral silane-based bond construction methodology to introduce t

Epothilones C, E and F

Epothilone derivatives are obtained by: (1) cultivation of Sorangium cellulosum DSM 6773 in the presence of an absorption resin; (2) separation of the resin and culture followed by washing with aqueous methanol; (3) eluting the washed resin with methanol and reducing the extract; (4) partitioning the extract between methanol and hexane; (5) reducing the methanolic phase and fractionating it on a Sephadex column, and (6) isolation of the epothilones by chromatography using a methanol/water mixture. Epothilone A is followed by epothilone B, and two further fractions.

Synthesis of epothilones, intermediates thereto, analogues and uses thereof

The present invention provides convergent processes for preparing epothilone A and B, desoxyepothilones A and B, and analogues thereof. Also provided are analogues related to epothilone A and B and intermediates useful for preparing same. The present invention further provides novel compositions based on analogues of the epothilones and methods for the treatment of cancer and cancer which has developed a multidrug-resistant phenotype.

Epothilone derivatives, their preparation and utilization

Epothilone derivatives of formula (I)-(III) are new. R = H or 1-4C alkyl; Y Z = H, halo, pseudohalogen, OH, 1-6C acyloxy, 1-6C alkoxy or benzoyloxy; or Y+Z = bond or O; (a) R' = Q; A = H; B = OR1; and R" = R2; or R"+B = C(O)O, C(S)O, S(O)O, Si(R")2O or C(

Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones

Enzymatic reactions catalyzed by DERA provide the basis for a new strategy for the synthesis of novel pyranose synthons. The utility of this very convergent and effective method is demonstrated by the concise total synthesis of epothilones (see scheme; DERA = 2-deoxyribose-5-phosphate aldolase).

Total synthesis of epothilone A through stereospecific epoxidation of the p-methoxybenzyl ether of epothilone C

The total synthesis of epothilone A is described by the coupling four segments 4 - 7a. Three of the segments, 4, 5 and 7a, have only one chiral center; all other chiral centers were introduced by simple asymmetric catalytic reactions. The key steps are the ring opening of epoxide 5 with acetylide 8 for the construction of the C12-C13 cis double bond and a practical hydrolytic kinetic resolution (HKR) developed by Jacobsen group for the introduction the chiral center at C3. Especially, the stereospecific epoxidation of 3-O-PMB epothilone C 3b through long-range effect of 3-O-PMB protecting group gave high yields of the C12 - C13 α-epoxide for the synthesis of target molecule.

Methodology based on chiral silanes in the synthesis of polypropionate-derived natural products - Total synthesis of epothilone A

Epothilones A and B (1 and 2) are natural products with potent antitumor activity. These compounds have a Taxol-like mechanism of action against tumor cells. A total synthesis of epothilone A (1) is reported, which is based on the synthesis and union of t

Stereoselective syntheses of epothilones A and B via nitrile oxide cycloadditions and related studies

The expedient and fully stereocontrolled synthesis of epothilones A and B are described. The routes described make extensive study of nitrile oxide cycloadditions as surrogates for aldol addition reactions and have led to the realization of a highly convergent synthesis based on the Kanemasa hydroxyl-directed nitrile oxide cycloaddition. As well, our synthetic efforts have led to the development of new reaction methodologies and served as the proving ground for several modern methods for asymmetric carbon-carbon bond formation.

Total synthesis of epothilone A

A convergent total synthesis of epothilone A (1) is described. The key steps are diastereoselective aldol condensation of aldehyde 3 to form the C6-C7 bond; macrolactonization and Wadsworth-Emmons reaction of methyl ketone with phosp

Synthesis and biological activity of novel epothilone aziridines.

[reaction: see text]. A series of 12alpha,13alpha-aziridinyl epothilone derivatives were synthesized in an efficient manner from epothilone A. The final semisynthetic route involves a formal double-inversion of stereochemistry at both the C12 and C13 posi