189453-35-8

Basic information

• Product Name: (4S,7R,8S,9S,13Z,16S)-4,8-Bis-{[tert-butyl(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxocyclohexadec-13-ene-2,6-dione
• Synonyms: (4S,7R,8S,9S,13Z,16S)-4,8-Bis-{[tert-butyl(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxocyclohexadec-13-ene-2,6-dione;[4S-[4R*,7S*,8R*,9R*,13Z,16R*(E)]]-4,8-Bis[[(1,1-diMethylethyl)diMethylsilyl]oxy]-
• CAS NO: 189453-35-8
• Molecular Formula: C₃₉H₆₉NO₅SSi₂
• Molecular Weight: 732.21556
• Product Categories: Chiral Reagents
• Mol File: 189453-35-8.mol
• Article Data: 20

Chemical Properties

• Boiling Point: 698.086°C at 760 mmHg
• Flash Point: 375.989°C
• Appearance: /
• Density: 1.013g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.502
• Solubility: Chloroform, Dichloromethane, Ethanol, Ethyl Acetate, Methanol, Toluene
• PKA: 2.56±0.10(Predicted)
• CAS DataBase Reference: (4S,7R,8S,9S,13Z,16S)-4,8-Bis-{[tert-butyl(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxocyclohexadec-13-ene-2,6-dione(CAS DataBase Reference)
• NIST Chemistry Reference: (4S,7R,8S,9S,13Z,16S)-4,8-Bis-{[tert-butyl(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxocyclohexadec-13-ene-2,6-dione(189453-35-8)
• EPA Substance Registry System: (4S,7R,8S,9S,13Z,16S)-4,8-Bis-{[tert-butyl(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxocyclohexadec-13-ene-2,6-dione(189453-35-8)

Safety Data

• Hazardous Substances Data: 189453-35-8(Hazardous Substances Data)

Usage

Description

(4S,7R,8S,9S,13Z,16S)-4,8-Bis-[tert-butyl(dimethyl)silyl]oxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxocyclohexadec-13-ene-2,6-dione is a complex organic compound with a unique molecular structure. It is characterized by its stereochemistry and functional groups, which contribute to its specific properties and potential applications.

Uses

Used in Pharmaceutical Industry:
(4S,7R,8S,9S,13Z,16S)-4,8-Bis-[tert-butyl(dimethyl)silyl]oxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxocyclohexadec-13-ene-2,6-dione is used as an intermediate in the synthesis of Epothilones. Epothilones are polyketide natural products that inhibit cancer cells by a mechanism similar to paclitaxel and are effective against paclitaxel-resistant tumors. Epothilone D is in phase I clinical testing in patients with advanced solid tumors. Epothilone D is a cytotoxic macrolide that stabilizes malignant cells' microtubules and arrests mitosis, a characteristic it shares with other epothilones. They bind to the same hepatic sites as does paclitaxel (Taxol) in a 1:1 stoichiometric ratio of α,β-tubulin heterodimers.
Chemical Properties:
The compound is described as a white foam, indicating its physical state and appearance.

InChI:InChI=1/C39H69NO5SSi2/c1-26-19-18-20-27(2)35(45-48(16,17)38(9,10)11)29(4)36(42)39(12,13)33(44-47(14,15)37(6,7)8)24-34(41)43-32(22-21-26)28(3)23-31-25-46-30(5)40-31/h21,23,25,27,29,32-33,35H,18-20,22,24H2,1-17H3/b26-21-,28-23+/t27-,29+,32-,33-,35?/m0/s1

Upstream product

• 189453-54-1 (Z)-(4S,6R,7S,8S,9S,16S)-4,8-Bis-(tert-butyl-dimethyl-silanyloxy)-6-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-en-2-one 
• 190369-96-1 (12Z,16E)-(3S,6R,7S,8S,15S)-3,7-Bis-(tert-butyl-dimethyl-silanyloxy)-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-thiazol-4-yl)-5-oxo-heptadeca-12,16-dienoic acid 
• 193146-26-8 (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis{[tert-butyl(dimethyl)silyl]oxy}-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxoheptadeca-12,16-dienoic acid 
• 197233-39-9 (1S)-1-[(E)-1-Methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-3-butenyl (3S,6R,7S,8S)-3,7-di-[tert-butyldimethylsilyloxy]-4,4,6,8,12-pentamethyl-5-oxo-12-tridecenoate 
• 69739-34-0 t-butyldimethylsiyl triflate 
• 189453-10-9 epothilone D 
• 187283-46-1 (S,E)-2-methyl-1-(2-methylthiazol-4-yl)hexa-1,5-dien-3-ol 
• 204195-20-0 (Z)-(4S,7R,8S,9S,16S)-4,8-Bis-(tert-butyl-dimethyl-silanyloxy)-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-oxacyclohexadec-13-ene-2,6-dione 
• 63928-37-0 diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate 
• 396092-18-5 (2S)-5-methyl-4-(phenylsulfonyl)hex-5-ene-1,2-diol 
• 331268-29-2 (3S)-3-(tert-butyldimethylsilyloxy)-4,4-dimethylheptane-1,5-diol 
• 396092-17-4 (5S)-5,6-(dimethylmethylene)dioxy-2-methylhex-1-en-3-yl phenyl sulfone 
• 396092-19-6 (2S)-1-tert-butyldimethylsilyloxy-5-methyl-4-(phenylsulfonyl)hex-5-en-2-ol 
• 396092-40-3 (2S,9S,4Z)-5,9-dimethyl-2-(2-trimethylsilylethoxy)methoxy-10-pivoyloxydec-4-enal 

Downstream Products

• 189453-10-9 epothilone D 
• 152044-54-7 epothilone B 
• 247230-49-5 (1S,3S,7S,10R,11S,12S,16S)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4-oxabicyclo[14.1.0]heptadecane-5,9-dione 
• 219989-84-1 ixabepilone 

Relevant articles and documents

The Total Synthesis of Epothilone D as a Yardstick for Probing New Methodologies

Here, a concise and highly convergent synthesis of epothilone D was investigated, relying on fragments of equal complexity that could be prepared in gram scale quantities. The strategy to construct the fragments includes the use of a previously reported enantiospecific zinc-catalyzed cross-coupling of an α-hydroxy ester triflate with a Grignard reagent, the application of a hydroboration/boron–magnesium exchange sequence for the rapid construction of the Z-substituted trisubstituted double bond present in the natural product, and a Noyori-type hydrogenation to install the β-hydroxy ester moiety of the southern part. The key to success is the diastereoselective head-to-tail macrolactonization by an intramolecular addition of the corresponding ω-alkynyl-substituted carboxylic acids to construct a new stereocenter in the macrocyclic core structure in one single step.

Epothilone D and its 9-Methyl analogues: Combinatorial syntheses, conformation, and biological activities

Epothilone D (Epo D) and its 9-Methyl conformational analogues were synthesized through a highly efficient combinatorial approach. The fragment E was synthesized in 11 total steps with 6 longest linear steps, and each aldehyde B was prepared via a 3-step sequence. Starting from the common precursor E and a suitable aldehydes B, each target molecule were obtained in only 4 steps. The 9-(S)-epo D and 9-(R)-epo D demonstrated significant difference in inhibition activities against cancer cell lines and in conformational analysis.

An efficient total synthesis of (-)-epothilone B

An efficient total synthesis of (-)-epothilone B has been achieved in ca. 8% yield over 11 steps from 9 (or 10 steps from 7/8), which features a bissiloxane-tethered ring closing metathesis reaction to approach the trisubstituted (Z) double bond and forms a new basis for further development of an industrial process for epothilone B and ixabepilone.