187527-25-9

Usage

Chemical Properties

Colourless Oil

InChI:InChI=1/C21H46O3Si2/c1-14-17(22)21(8,9)18(24-26(12,13)20(5,6)7)15-16-23-25(10,11)19(2,3)4/h18H,14-16H2,1-13H3/t18-/m0/s1

Upstream product

• 18162-48-6 tert-butyldimethylsilyl chloride 
• 250679-53-9 (5S)-5-{[(tert-butyl)dimethylsilyl]oxy}-7-hydroxy-4,4-dimethylheptan-3-one 
• 218614-14-3 (4S)-4,6-bis{[tert-butyl(dimethyl)silyl]oxy}-3,3-dimethylhexan-2-one 
• 74-88-4 methyl iodide 
• 255398-79-9 (-)-(5S)-5,7-bis(tert-butyldimethylsilyloxy)-4,4-dimethylheptan-3-ol 
• 925-90-6 ethylmagnesium bromide 
• 355009-17-5 3,5-bis-(tert-butyl-dimethyl-silanyloxy)-2,2-dimethyl-pentanoic acid phenyl ester 
• 106921-60-2 2,2-dimethyl-3-oxopentanal 
• 250679-52-8 (3S)-3-[((tert-butyl)dimethylsilyl)oxy]-1-[(1S,5R)-10,10-dimethyl-3,3-dioxido-3-thia-4-azatricyclo[5.2.1.0^1.5]dec-4-yl]-4,4-dimethylheptan-1,5-dione 
• 250679-51-7 (3S)-1-[(1S,5R)-10,10-dimethyl-3,3-dioxido-3-thia-4-azatricyclo[5.2.1.0^1.5]dec-4-yl]-3-hydroxy-4,4-dimethylheptan-1,5-dione 
• 73842-99-6 3-tert-butyldimethylsilyloxy-1-propanol 
• 66582-32-9 3-(benzyloxy)-2,2-dimethylpropan-1-ol 
• 38216-93-2 3-benzyloxypivalic aldehyde 
• 121352-87-2 (E)-5-(benzyloxy)-4,4-dimethylpent-2-en-1-ol 

Downstream Products

• 193146-49-5 (7S,10R,11S,12S,19S,Z)-7-(tert-butyldimethylsilyloxy)-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4,20-dioxa-3,21-disilatricos-16-en-9-one 
• 187527-24-8 (2S,3S,4R,7S)-1-benzyloxy-7,9-bis(tert-butyldimethylsilyloxy)-3-hydroxy-2,4,6,6-tetramethylnonan-5-one 
• 252986-95-1 (12E,16E)-(3S,6R,7S,8S,15S)-1,3,15-Tris-(tert-butyl-dimethyl-silanyloxy)-7-hydroxy-4,4,6,8-tetramethyl-17-(2-methyl-thiazol-4-yl)-12-trityloxymethyl-heptadeca-12,16-dien-5-one 
• 371785-05-6 (3S,6R,7S,8S)-11-((1R,2R)-2-Benzyloxymethyl-cyclopropyl)-1,3-bis-(tert-butyl-dimethyl-silanyloxy)-7-hydroxy-4,4,6,8-tetramethyl-undecan-5-one 
• 371784-99-5 (3S,6R,7S,8S)-11-((1S,2R)-2-Benzyloxymethyl-cyclopropyl)-1,3-bis-(tert-butyl-dimethyl-silanyloxy)-7-hydroxy-4,4,6,8-tetramethyl-undecan-5-one 
• 472962-04-2 (3S,6R,7S,8S)-11-((1R,2R)-2-Benzyloxymethyl-1-methyl-cyclopropyl)-1,3-bis-(tert-butyl-dimethyl-silanyloxy)-7-hydroxy-4,4,6,8-tetramethyl-undecan-5-one 
• 308357-88-2 (3S,6R,7S,8S,12Z,15S,16E)-1,3-bis{[tert-butyl(dimethyl)silyl]oxy}-7-hydroxy-15-[(4-methoxybenzyl)oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)heptadeca-12,16-dien-5-one 
• 488791-49-7 (12Z,16E)-(3S,6R,7S,8S,14S,15S)-15-(tert-Butoxy-diphenyl-silanyloxy)-3,7-bis-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-4,4,6,8,12,14,16-heptamethyl-17-(2-methyl-thiazol-4-yl)-heptadeca-12,16-dien-5-one 
• 488791-46-4 (12Z,16E)-(3S,6R,7S,8S,14R,15S)-15-(tert-Butoxy-diphenyl-silanyloxy)-1,3,7-tris-(tert-butyl-dimethyl-silanyloxy)-4,4,6,8,12,14,16-heptamethyl-17-(2-methyl-thiazol-4-yl)-heptadeca-12,16-dien-5-one 
• 488791-47-5 (12Z,16E)-(3S,6R,7S,8S,14S,15S)-15-(tert-Butoxy-diphenyl-silanyloxy)-1,3,7-tris-(tert-butyl-dimethyl-silanyloxy)-4,4,6,8,12,14,16-heptamethyl-17-(2-methyl-thiazol-4-yl)-heptadeca-12,16-dien-5-one 
• 152044-54-7 epothilone B 
• 189453-35-8 (4S,7R,8S,9S,13Z,16S,1'E)-4,8-di-tert-butyldimethylsilyloxy-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-1-oxa-13-cyclohexadecene-2,6-dione 
• 189453-10-9 epothilone D 
• 193146-53-1 (5S,8R,9S,10S,17S,Z)-9-(tert-butyldimethylsilyloxy)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4,18-dioxa-3,19-disilahenicos-14-en-7-one 

Relevant academic research and scientific papers

Total synthesis and evaluation of C26-hydroxyepothilone D derivatives for photoaffinity labeling of β-tubulin

(Chemical Equation Presented) Three photaffinity labeled derivatives of epothilone D were prepared by total synthesis, using efficient novel asymmetric synthesis methods for the preparation of two important synthetic building blocks. The key step for the asymmetric synthesis of (S,E)-3-(tert- butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)pent-4-enal involved a ketone reduction with (R)-Me-CBS-oxazaborolidine. For the synthesis of (5S)-5,7-di[(tert-butyldimethylsilyl)oxy]-4,4-dimethylheptan-3-one an asymmetric Noyori reduction of a β-ketoester was employed. The C26 hydroxyepothilone D derivative was constructed following a well-established total synthesis strategy and the photoaffinity labels were attached to the C26 hydroxyl group. The photoaffinity analogues were tested in a tubulin assembly assay and for cytotoxicity against MCF-7 and HCT-116 cancer cell lines. The 3- and 4-azidobenzoic acid analogues were found to be as active as epothilone B in a tubulin assembly assay, but demonstrated significantly reduced cellular cytotoxicity compared to epothilone B. The benzophenone analogue was inactive in both assays. Docking and scoring studies were conducted that suggested that the azide analogues can bind to the epothilone binding site, but that the benzophenone analogue undergoes a sterically driven ligand rearrangement that interrupts all hydrogen bonding and therefore protein binding. Photoaffinity labeling studies with the 3-azidobenzoic acid derivative did not identify any covalently labeled peptide fragments, suggesting that the phenylazido side chain was predominantly solvent-exposed in the bound conformation. 2009 American Chemical Society.

Total synthesis and selective activity of a new class of conformationally restrained epothilones

Stereoselective total syntheses of two novel conformationally restrained epothilone analogues are described. Evans asymmetric alkylation, Brown allylation, and a diastereoselective aldol reaction served as the key steps in the stereoselective synthesis of

CONFORMATIONALLY RESTRAINED EPOTHILONE ANALOGUES AS ANTI-LEUKEMIC AGENTS

A method for synthesizing anti-leukemic epothilone analogues includes rigidifying a region between the macrolactone ring and the aromatic side-chain. The anti-leukemic compositions are non-naturally occurring epothilone analogue that are rigidified between the macrolactone ring and the aromatic side-chain.

EPOTHILONE ANALOGUES

Epothilone analogues include a molecular scaffold which holds at least one segment of epothilone in a predetermined orientation and which rigidities a region between the macrolactone ring and the aromatic side-chain.

Conformation-activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone

The conformation-activity relationships for the biologically active polyketide, epothilone, have been determined. Computer-based molecular modeling and high field NMR techniques have provided the solution preferences for epothilones 1 and 2. For the C1-C8

Multi-step application of immobilized reagents and scavengers: A total synthesis of epothilone C

The total synthesis of the cytotoxic antitumour natural product epothilone C has provided a stage for the exploitation and further development of immobilized reagent methods. A stereoselective convergent synthetic strategy was applied, incorporating polymer-supported reagents, catalysts, scavengers and catch-and-release techniques to avoid frequent aqueous work-up and chromatographic purification.

Total syntheses of epothilones B and D

A convergent, total synthesis of epothilones B (2) and D (4) is described. The key steps are Normant coupling to establish the desired (Z)-stereochemistry at C12-C13, Wadsworth-Emmons olefination of methyl ketone 28 with the phosphonate ester 8, diastereoselective aldol condensation of aldehyde 5 with the enolate of keto acid derivatives to form the C6-C7 bond, selective deprotection of acid 52, and macrolactonization.

A total synthesis of epothilones using solid-supported reagents and scavengers

A total synthesis of epothilone C(1) with concomitant formal synthesis of epothilone A is described, using immobilized reagents and scavengers to effect multistep synthetic transformations and purifications.

Method for producing epothilone B and derivatives, and intermediate products for this method

The invention relates to a method for producing epothilone B and derivatives, and to intermediate products for this method. According to the novel method, the epothilone B or derivatives are produced in high yields from the C1-C6, C7-C10 and C11-C20-fragm

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.