- Total synthesis of epothilone A.
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[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
- Zhu,Panek
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Read Online
- Epothilones C, E and F
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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.
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- Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones
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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).
- Liu, Junjie,Wong, Chi-Huey
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p. 1404 - 1407
(2007/10/03)
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- Total synthesis of epothilone A through stereospecific epoxidation of the p-methoxybenzyl ether of epothilone C
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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.
- Liu, Zhi-Yu,Chen, Ze-G,Yu, Cheng-Zhi,Wang, Rui-Fang,Zhang, Ru-Zhou,Huang, Chu-Sheng,Yan, Zheng,Cao, De-Rong,Sun, Jian-Bo,Li, Gang
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p. 3747 - 3756
(2007/10/03)
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- Epothilone derivatives, their preparation and utilization
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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(
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- Synthesis of epothilones, intermediates thereto, analogues and uses thereof
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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.
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Page column 37
(2010/01/31)
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- Stereoselective syntheses of epothilones A and B via nitrile oxide cycloadditions and related studies
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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.
- Bode,Carreira
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p. 6410 - 6424
(2007/10/03)
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- Total synthesis of epothilone A
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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
- Hindupur, Rama M,Panicker, Bijoy,Valluri, Muralikrishna,Avery, Mitchell A
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p. 7341 - 7344
(2007/10/03)
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- Methodology based on chiral silanes in the synthesis of polypropionate-derived natural products - Total synthesis of epothilone A
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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
- Zhu, Bin,Panek, James S.
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p. 1701 - 1714
(2007/10/03)
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- Synthesis and biological activity of novel epothilone aziridines.
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[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
- Regueiro-Ren,Borzilleri,Zheng,Kim,Johnson,Fairchild,Lee,Long,Vite
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p. 2693 - 2696
(2007/10/03)
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- Enantioselective total synthesis of epothilone A using multifunctional asymmetric catalyses
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A catalytic version has now been developed for the enantioselective total synthesis of epothilone A (1). The key is the use of multifunctional asymmetric catalySes for a direct aldol reaction and cyanosilylation. This successful approach demonstrated the usefulness of these reactions for the catalytic asymmetric synthesis of complex molecules.
- Sawada, Daisuke,Shibasaki, Masakatsu
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p. 209 - 213
(2007/10/03)
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- Enantioselective total synthesis of epothilones A and B using multifunctional asymmetric catalysis
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An enantioselective total synthesis of epothilones A (1) and B (2) using multifunctional asymmetric catalysis such as a cyanosilylation of an aldehyde, an aldol reaction of an unmodified ketone with an aldehyde, and a protonation in the conjugate addition of a thiol to an α,β-unsaturated thioester has been achieved. We divided 1 and 2 into fragment A, fragment B, and fragment C. A catalytic asymmetric synthesis of fragments A and B was accomplished using a catalytic asymmetric cyanosilylation as a key step. An enantiocontrolled synthesis of fragment C was achieved in two ways. One is the use of a direct catalytic asymmetric aldol reaction of an unmodified ketone with an aldehyde as a key step, and the other utilizes a catalytic asymmetric protonation in the conjugate addition of a thiol to an α,β-unsaturated thioester as a key step. Suzuki cross-coupling of fragment A with fragment C followed by Yamaguchi lactonization as key steps led to an enantiocontrolled synthesis of epothilone A (1). On the other hand, Suzuki cross-coupling of fragment B with fragment C followed by Yamaguchi lactonization accomplished an enantiocontrolled synthesis of epothilone B (2).
- Sawada, Daisuke,Kanai, Motomu,Shibasaki, Masakatsu
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p. 10521 - 10532
(2007/10/03)
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- Total synthesis of (-)-epothilone A
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The total synthesis of (-)-epothilone A by a convergent route is reported. The synthesis of the required key intermediates has been improved with respect to stereoselectivity and availability. The access to ethyl ketone 2 has been significantly improved b
- Schinzer, Dieter,Bauer, Armin,Boehm, Oliver M.,Limberg, Anja,Cordes, Martin
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p. 2483 - 2491
(2007/10/03)
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- Total Synthesis of Epothilones A and B
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Convergent, stereocontrolled total syntheses of the microtubule-stabilizing macrolides epothilones A (2) and B (3) have been achieved. Four distinct ring-forming strategies were pursued (see Scheme 1). Of these four, three were reduced to practice. In one approach, the action of a base on a substance possessing an acetate ester and a nonenolazable aldehyde brought about a remarkably effective macroaldolization see (89 -> 90 + 91; 99 -> 100 + 101), simultaneously creating the C2-C3 bond and the hydroxyl-bearing stereocenter at C-3. Alternatively, the 16-membered macrolide of the epothilones could be fashioned through a C12-C13 ring-closing olefin metathesis (e.g. see 111 -> 90 + 117; 122 -> 105 + 123) and through macrolactonization of the appropriate hydroxy acid (e.g. see 88 -> 93). The application of a stereospecific B-alkyl Suzuki coupling strategy permitted the establishment of a cis-C12-C13 olefin, thus setting the stage for an eventual site- and diastereoselective epoxidation reaction (see 96 -> 2; 106 -> 3). The development of a novel cyclopropane solvolysis strategy for incorporating the geminal methyl groups of the epothilones (see 39 -> 40 -> 41), and the use of Lewis acid catalyzed diene-aldehyde cyclocondensation (LACDAC) (see 35 + 36 -> 37) and asymmetric allylation (see 10 -> 76) methodology are also noteworthy.
- Dongfang, Meng,Bertinato, Peter,Balog, Aaron,Su, Dai-Shi,Kamenecka, Ted,et al.
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p. 10073 - 10092
(2007/10/03)
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- Total synthesis of epothilone A: The olefin metathesis approach
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A flexible alterative route to the total synthesis of the antitumor agent epothilone A has been achieved by a highly convergent strategy involving olefin metathesis as a key step. The strategy may allow the chemical synthesis of a library of designed epothilones for biological screening.
- Yang,He,Vourloumis,Vallberg,Nicolau
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p. 166 - 168
(2007/10/03)
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- The olefin metathesis approach to epothilone A and its analogues
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The olefin metathesis approach to epothilone A (1) and several analogues (39-41, 42-44, 51-57, 58-60, 64-65, and 67-69) is described. Key building blocks 6-8 were constructed in optically active form and were coupled and elaborated to olefin metathesis pr
- Nicolaou,He,Vourloumis,Vallberg,Roschangar,Sarabia,Ninkovic,Yang,Trujillo
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p. 7960 - 7973
(2007/10/03)
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- Total syntheses of epothilones A and B via a macrolactonization-based strategy
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The total syntheses of epothilones A (1) and B (2) and several analogues thereof are described. The reported strategy relies on a macrolactonization approach and features selective epoxidation of the macrocycle double bond in precursors 3 and 4 (Scheme 1), respectively, as well as high convergency and flexibility. Building blocks 9-12 and 15 were constructed by asymmetric processes and coupled via Wittig, aldol, and macrolactonization reactions to afford the basic skeleton of epothilones and that of several of their analogues by a relatively short route. The utilization ofintermediate 14, obtained via a stereoselective Wittig reaction and its Enders coupling to SAMP hydrazone 13 (Scheme 8), in combination with a stereoselective aldol reaction with the modified substrate 69 (Scheme 10) improved the stereoselectivity and efficiency of the total synthesis of these new and highly potent microtubule binding antitumor agents.
- Nicolaou,Ninkovic,Sarabia,Vourloumis,He,Vallberg,Finlay,Yang
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p. 7974 - 7991
(2007/10/03)
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- Totalsynthese von (-)-Epothilon A
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Keywords: Cyclisierungen; Epothilone; C-C-Kupplungen; Naturstoffe; Synthesemethoden
- Balog, Aaron,Meng, Dongfang,Kamenecka, Ted,Bertinato, Peter,Su, Dai-Shi,et al.
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p. 2976 - 2978
(2007/10/03)
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