106921-60-2Relevant articles and documents
Synthesis of C1-C6 fragment for epothilone A via lipase-catalyzed optical resolution
Shioji,Kawaoka,Miura,Okuma
, p. 3569 - 3575 (2001)
Synthesis of 5-oxo-(3S)-hydroxy-4,4-dimethylheptanoic acid (1), C1-C6 fragment of epothilone A, is described. Racemic tert-butyl 5-oxo-(3S)-acetoxy-4,4-dimethylheptanoate (5) was prepared by acylation of enamine followed by aldol condensation. Optical resolution of the heptanoate 5 was carried out by lipase catalyzed hydrolysis (yield 50%, > 98% e.e.).
EPOTHILONE ANALOGUES
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Page/Page column 35; 5/22, (2008/06/13)
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.
Epothilon derivatives, method for the production and the use thereof as pharmaceuticals
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Page/Page column 58-59, (2010/10/19)
Disclosed are epothilone compounds of formula I, which are useful as pharmaceutical compounds for treating, for example, malignant tumors and chronic inflammatory diseases and are useful in anti-angiogenesis therapy.
Studies towards the synthesis of epothilone A via organoboranes
Ramachandran, P. Veeraraghavan,Chandra, J. Subash,Prabhudas, Bodhuri,Pratihar, Debarshi,Reddy, M. Venkat Ram
, p. 3812 - 3824 (2007/10/03)
Studies towards the synthesis of epothilone A via organoboranes have been described. A modified procedure for the large-scale preparation of B-γ,γ-dimethylallyldiisopinocampheylborane from prenyl alcohol has been developed. This reagent, upon reaction wit
Total syntheses of epothilones B and D
Jung, Jae-Chul,Kache, Rajashaker,Vines, Kimberly K.,Zheng, Yan-Song,Bijoy, Panicker,Valluri, Muralikrishna,Avery, Mitchell A.
, p. 9269 - 9284 (2007/10/03)
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.
EPOTHILONE DERIVATIVES, METHOD FOR PRODUCING SAME AND THEIR PHARMACEUTICAL USE
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, (2008/06/13)
This invention relates to the new epothilone derivatives of general formula I, 1in which substituents Y, Z R2a, R2b, R3, R4a, R4b, D—E, R5, R6, R7, R8 and X have the meanings that are indicated in more detail in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanomas, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (psoriasis, arthritis). To avoid uncontrolled proliferation of cells and for better compatibility of medical implants, they can be applied or introduced into polymer materials. The compounds according to the invention can be used alone or to achieve additive or synergistic actions in combination with other principles and classes of substances that can be used in tumor therapy.
Epothilone derivatives
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, (2008/06/13)
The present invention relates to epothilone derivatives, having the following formula in which the variables G, W, Q, X, Y, B1, B2, Z1, Z2, and R1-R7are as defined herein, methods for the preparation of the derivatives and intermediates thereof.
The total synthesis and biological assessment of trans-epothilone A
Altmann, Karl-Heinz,Bold, Guido,Caravatti, Giorgio,Denni, Donatienne,Floersheimer, Andreas,Schmidt, Alfred,Rihs, Grety,Wartmann, Markus
, p. 4086 - 4110 (2007/10/03)
The total synthesis of (12S,13S)-trans-epothilone A (1a) was achieved based on two different convergent strategies. In a first-generation approach, construction of the C(11)-C(12) bond by Pd0-catalyzed Negishi-type coupling between the C(12)-to-C(15) trans-vinyl iodide 5 and the C(7)-to-C(11) alkyl iodide 4 preceded the (nonselective) formation of the C(6)-C(7) bond by aldol reaction between the C(7)-to-C(15) aldehyde 25 and the dianion derived from the C(1)-to-C(6) acid 3. The lack of selectivity in the aldol step was addressed in a second-generation approach, which involved construction of the C(6)-C(7) bond in a highly diastereoselective fashion through reaction between the acetonide-protected C(l)-to-C(6) diol 31 ('Schinzer's ketone') and the C(7)-to-C(11) aldehyde 30. As part of this strategy, the C(11)-C(12) bond was established subsequent to the critical aldol step and was based on B-alkyl Suzuki coupling between the C(1)-to-C(11) fragment 40 and C(12)-to-C(15) trans-vinyl iodide 5. Both approaches converged at the stage of the 3-O, 7-O-bis-TBS-protected seco acid 27, which was converted to trans-deoxyepothilone A (2) via Yamaguchi macrolactonization and subsequent deprotection. Stereoselective epoxidation of the trans C(12)-C(13) bond could be achieved by epoxidation with Oxone in the presence of the catalyst 1,2:4,5-di-O-isopropylidene-L-erythro-2,3-hexodiuro-2,6-pyranose (42a), which provided a 8:1 mixture of 1a and its (12R,13R)-epoxide isomer 1b in 27% yield (54% based on recovered starting material). The absolute configuration of 1a was established by X-ray crystallography. Compound 1a is at least equipotent with natural epothilone A in its ability to induce tubulin polymerization and to inhibit the growth of human cancer cell lines in vitro. In contrast, the biological activity of 1b is at least two orders of magnitude lower than that of epothilone A or 1a.