scholarly journals Epothilone A

2020 ◽  
Author(s):  
Keyword(s):  
Epothilone A

ChemInform Abstract: Total Synthesis of (-)-Epothilone A.

ChemInform ◽  
2010 ◽  
Vol 28 (23) ◽  
pp. no-no
Author(s):  
D. SCHINZER ◽  
A. LIMBERG ◽  
A. BAUER ◽  
O. M. BOEHM ◽  
M. CORDES
Keyword(s):  
Total Synthesis ◽  
Epothilone A

A Scalable Approach for the Synthesis of Epothilone Thiazole Fragment (C12–C21 unit) Via Wacker Oxidation

Synlett ◽  
2018 ◽  
Vol 29 (08) ◽  
pp. 1076-1078
Author(s):  
Jayaprakash Yerrabelly ◽  
Rajashekar Kommera ◽  
Venkateshwer Kasireddy ◽  
Venkat Ghojala ◽  
Markandeya Bekkam ◽  
...  
Keyword(s):  
Wittig Reaction ◽  
Chemical Modifications ◽  
Wacker Oxidation ◽  
Epothilone A ◽  
Palladium Catalyzed ◽  
The Common ◽  
Scalable Synthesis ◽  
Reaction Result ◽  
Chiral Synthon

A new scalable synthesis of the common thiazole fragment (C12–C21 unit) of epothilone family of molecules (epothilone A–D) has been developed via palladium-catalyzed Wacker oxidation as a key step using (S)-2,2,3,3,9,9,10,10-octamethyl-5-vinyl-4,8-dioxa-3,9-disilaundecane, which has been prepared from commercially available chiral synthon (R)-ethyl-4-cyano-3-hydroxybutanoate. Then further chemical modifications using Horner–Wadsworth–Emmons reaction and Wittig reaction result in the common thiazole fragment (C12–C21 unit) in good yields.

scholarly journals Design and Synthesis of C6−C8 Bridged Epothilone A

2008 ◽  
Vol 10 (8) ◽  
pp. 1565-1568 ◽  
Author(s):  
Weiqiang Zhan ◽  
Yi Jiang ◽  
Peggy J. Brodie ◽  
David G. I. Kingston ◽  
Dennis C. Liotta ◽  
...  
Keyword(s):  
Design And Synthesis ◽  
Epothilone A

Epoxide opening with acetylide for synthesis of epothilone A C7–21 segment

1998 ◽  
Vol 39 (29) ◽  
pp. 5261-5264 ◽  
Author(s):  
Zhi-yu Liu ◽  
Chen-zhi Yu ◽  
Rui-Fang Wang ◽  
Gang Li
Keyword(s):  
Epothilone A ◽  
Epoxide Opening

The Keck Synthesis of Epothilone B

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Total Synthesis ◽  
Secondary Alcohol ◽  
Allylic Alcohol ◽  
Ring Closing Metathesis ◽  
Relative Configuration ◽  
University Of Utah ◽  
Epothilone B ◽  
Hydride Reduction ◽  
Epothilone A ◽  
The University

The total synthesis of Epothilone B 4, the first natural product (with Epothilone A) to show the same microtubule-stabilizing activity as paclitaxel (Taxol®), has attracted a great deal of attention since that activity was first reported in 1995. The total synthesis of 4 devised (J. Org. Chem. 2008, 73, 9675) by Gary E. Keck of the University of Utah was based in large part on the stereoselective allyl stannane additions (e.g. 1 + 2 → 3 ) that his group originated. The allyl stannane 2 was prepared from the acid chloride 5. Exposure of 5 to Et3N generated the ketene, that was homologated with the phosphorane 6 to give the allene ester 7. Cu-mediated conjugate addition of the stannylmethyl anion 8 then delivered 2. The silyloxy aldehyde 1 was prepared from the ester 9 by reduction with Dibal. Felkincontrolled 1,2-addition of the allyl stannane 2 established the relative configuration of the secondary alcohol of 3, that was then used to control the relative configuration of the new alcohol in 10. Addition of the crotyl borane 12 to the derived aldehyde 11 also proceeded with high diastereocontrol. The other component of 4 was prepared from the aldehyde 14. Enantioselective allylation, by the method the authors developed, delivered the alcohol 16. The Z trisubstituted alkene was then assembled by condensing the aldehyde 17 with the phosphorane 18. Dibal reduction of the product lactone 19 gave a diol, the allylic alcohol of which was selectively converted to the chloride with the Corey-Kim reagent. Hydride reduction then delivered the desired homoallylic alcohol, that was converted to the phosphonium salt 21. Condensation of 21 with 13 gave the diene, that was carried on to Epothilone B 4. The synthesis of Epothilone B 4 as originally conceived by the authors depended on ring-closing metathesis of the triene 22. They prepared 22, but on exposure to the second-generation Grubbs catalyst it was converted only to 23. The authors concluded that the trans acetonide kept 22 in a conformation that did not allow the desired macrocyclization.

Epothilone A-D and their thiazole-modified analogs as novel anticancer agents

1999 ◽  
Vol 71 (11) ◽  
pp. 2019-2024 ◽  
Author(s):  
G. Höfle ◽  
N. Glaser ◽  
T. Leibold ◽  
M. Sefkow
Keyword(s):  
Anticancer Agents ◽  
Epothilone A

scholarly journals On the Importance of the Thiazole Nitrogen in Epothilones: Semisynthesis and Microtubule-Binding Affinity of Deaza-Epothilone C

Chemistry ◽  
2020 ◽  
Vol 2 (2) ◽  
pp. 499-509
Author(s):  
Adriana Edenharter ◽  
Lucie Ryckewaert ◽  
Daniela Cintulová ◽  
Juan Estévez-Gallego ◽  
José Fernando Díaz ◽  
...  
Keyword(s):  
Decisive Role ◽  
Ring Closure ◽  
Side Chain ◽  
Microtubule Binding ◽  
Acid Fragment ◽  
Epothilone A ◽  
Thiophene Moiety ◽  
Free Energy Of Binding

Deaza-epothilone C, which incorporates a thiophene moiety in place of the thiazole heterocycle in the natural epothilone side chain, has been prepared by semisynthesis from epothilone A, in order to assess the contribution of the thiazole nitrogen to microtubule binding. The synthesis was based on the esterification of a known epothilone A-derived carboxylic acid fragment and a fully synthetic alcohol building block incorporating the modified side chain segment and subsequent ring-closure by ring-closing olefin metathesis. The latter proceeded with unfavorable selectivity and in low yield. Distinct differences in chemical behavior were unveiled between the thiophene-derived advanced intermediates and what has been reported for the corresponding thiazole-based congeners. Compared to natural epothilone C, the free energy of binding of deaza-epothilone C to microtubules was reduced by ca. 1 kcal/mol or less, thus indicating a distinct but non-decisive role of the thiazole nitrogen in the interaction of epothilones with the tubulin/microtubule system. In contrast to natural epothilone C, deaza-epothilone C was devoid of antiproliferative activity in vitro up to a concentration of 10 μM, presumably due to an insufficient stability in the cell culture medium.

Induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone A and B

2013 ◽  
Vol 27 (1) ◽  
pp. 239-249 ◽  
Author(s):  
Aneta Rogalska ◽  
Agnieszka Marczak ◽  
Arkadiusz Gajek ◽  
Marzena Szwed ◽  
Agnieszka Śliwińska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Anticancer Compounds ◽  
Epothilone A ◽  
Induction Of Apoptosis
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