186692-73-9

Usage

Uses

1. Used in Pharmaceutical Industry:
Oxacyclohexadec-13-ene-2,6-dione, 4,8-dihydroxy-5,5,7,9-tetramethyl-16-(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl-, (4S,7R,8S,9S,13Z,16S)is used as a potential therapeutic agent for various medical conditions due to its unique molecular structure and stereochemistry. Its ability to interact with specific biological targets makes it a promising candidate for the development of new drugs.
2. Used in Anticancer Applications:
Similar to Epothilone C, a related compound, Oxacyclohexadec-13-ene-2,6-dione, 4,8-dihydroxy-5,5,7,9-tetramethyl-16-(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl-, (4S,7R,8S,9S,13Z,16S)may exhibit antineoplastic properties and antitubulin activity. It could potentially be utilized in the development of novel antineoplastic agents, especially for cancer cells that are resistant to conventional treatments.
3. Used in Drug Delivery Systems:
The compound's unique structure and functional groups may allow for its incorporation into drug delivery systems, enhancing the bioavailability and targeting of therapeutic agents. This could lead to the development of more effective treatments with reduced side effects, particularly for cancer and other complex diseases.
4. Used in Chemical Research:
Due to its complex structure and stereochemistry, Oxacyclohexadec-13-ene-2,6-dione, 4,8-dihydroxy-5,5,7,9-tetramethyl-16-(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl-, (4S,7R,8S,9S,13Z,16S)may also be used as a research tool in the field of organic chemistry, biochemistry, and pharmacology. It could help scientists better understand the interactions between complex molecules and biological systems, leading to the discovery of new therapeutic strategies and drug candidates.

Upstream product

• 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 
• 331268-23-6 (S)-5-((tert-butyldimethylsilyl)oxy)-4,4-dimethyl-7-((triethylsilyl)oxy)heptan-3-one 
• 188259-76-9 (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-tetramethyl-5-oxo-12-tridecenoate 
• 186692-84-2 (4S,7R,8S,9S,16S)-4,8-bis-(tert-butyldimethylsilanyloxy)-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-vinyl]-(13Z)-1-oxacyclohexadec-13-ene-2,6-dione 
• 250679-53-9 (5S)-5-{[(tert-butyl)dimethylsilyl]oxy}-7-hydroxy-4,4-dimethylheptan-3-one 
• 193146-29-1 (3S)-3-(tert-butyl-dimethyl-silanyloxy)-4,4-dimethyl-5-oxo-heptanal 
• 187283-44-9 (5S)-5-(tert-butyl-dimethyl-silanyloxy)-4,4-dimethyloct-7en-3-one 
• 187283-43-8 (5S)-5-hydroxy-4,4-dimethyloct-7en-3-one 
• 188899-09-4 (3S,6R,7S,8S)-3,7-Di-(tert-butyldimethylsilyloxy)-1-hydroxy-4,4,6,8-tetramethyl-12-tridecen-5-one 
• 220200-50-0 4-[(1E,5Z)-(S)-3-(tert-Butyl-dimethyl-silanyloxy)-6-iodo-2-methyl-hexa-1,5-dienyl]-2-methyl-thiazole 
• 267877-81-6 Acetic acid (S)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-but-3-ynyl ester 
• 267877-84-9 4-[(E)-(S)-3-(tert-Butyl-dimethyl-silanyloxy)-2-methyl-penta-1,4-dienyl]-2-methyl-thiazole 
• 267877-86-1 Acetic acid (S)-1-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-but-3-ynyl ester 
• 267877-79-2 4-[(E)-3-hydroxy-2-methylhex-1-en-5-yn-1-yl]-2-methyl-1,3-thiazole 

Downstream Products

• 152044-53-6 epithilone A 
• 193071-75-9 [1R,3S,7S,10R,11S,12S,16S]-7,11-dihydroxy-8,8,10,12-tetramethyl-3-[(E)-1-[2-methylthiazol-4-yl]prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione 
• 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 

Relevant academic research and scientific papers

Synthesis, structure proof, and biological activity of epothilone cyclopropanes.

[structure--see text] A semisynthetic route to epothilone cyclopropanes from epothilones A and B is described. Of significance, the deoxygenation of the 12, 13-epoxide to give the corresponding olefin was achieved with high efficiency. The title compounds (8, 9) were active in both tubulin polymerization and cytotoxicity assays, which is in direct contrast to a previously published report. These results provide further evidence that the role of the 12,13-epoxide of epothilones is largely conformational and argue against some of the current pharmacophore models.

Concise total syntheses of epothilone A and C based on alkyne metathesis

A ring closing alkyne metathesis reaction catalyzed by the molybdenum complex 26 followed by a Lindlar reduction of the resulting cycloalkyne product opens an efficient and stereoselective entry into epothilone A and C.

Epothilone C macrolactonization and hydrolysis are catalyzed by the isolated thioesterase domain of epothilone polyketide synthase

Epothilone C is produced by the combined action of one nonribosomal peptide synthetase (NRPS) and nine polyketide synthase (PKS) modules in a multienzyme system. The final step in the biosynthesis is the thioesterase (TE)-catalyzed cyclorelease of epothilone from the EpoF protein. It has been unclear whether isolated PKS TE domains could exhibit macrolactonization activity. Here we demonstrate that the excised epothilone TE domain can catalyze the efficient cyclization of the N-acetylcysteamine thioester of seco-epothilone C to generate epothilone C (kcat/KM = 0.41 ± 0.03 min-1 mM-1). The TE domain also catalyzes the hydrolysis of both the N-acetylcysteamine thioester of seco-epothilone C (kcat = 0.087 ± 0.005 min-1, KM = 291 ± 53 μM) and that of the epothilone C (kcat = 0.67 ± 0.01 min-1, KM = 117 ± 5 μM) to form seco-epothilone C. Copyright

Total synthesis of epothilone A: The macrolactonization approach

This highly convergent and practical total synthesis of the antitumor agent epothilone A uses a macrolactonization as the key step. The strategy may provide access to a variety of epothilones desirable for biological screening.

Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: Applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A

The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol % of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73 % Z) epilachnene (15-membered ring: 91 % Z), ambrettolide (17-membered ring: 91 % Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97 % Z), and nakadomarin A (15-membered ring: up to 97 % Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule.

Z-SELECTIVE RING-CLOSING METATHESIS REACTIONS

The present invention relates generally to olefin metathesis. In some embodiments, the present invention provides methods for Z-selective ring-closing metathesis.

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.

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.

12, 13-cyclopropane epothilone derivatives

The present invention relates to 12,13-position modified epothilone derivatives, methods of preparation of the derivatives and intermediates therefor.

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.