CAS: 152044-53-6; (1R,5S,6S,7R,10S,14S,16S)-6,10-Dihydroxy-5,7,9,9-Tetramethyl-14-[(E)-1-(2-Methyl-1,3-Thiazol-4-yl)Prop-1-En-2-Yl]-13,17-Dioxabicyclo[14.1.0]Heptadecane-8,12-Dione

上下游产品

desoxyepothilone A (7S)-(tert-butyl-dimethyl-silanyloxy)-(11S)-hydroxy-8,8,(10R,12S)-tetramethyl-(3S)-[1-methyl-(2E)-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione (1S,3S,7S,10R,11S,12S,16R)-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-11-hydroxy-7-(4-methoxybenzyloxy)-8,8,10,12-tetramethyl-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione (4S,7R,8S,16S)-8-hydroxy-4-(4-methoxybenzyloxy)-5,5,7,9-tetramethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-1-oxacyclohexadec-13-en-2,6-dione desoxyepothilone A [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

(1E,3Z)-1-甲氧基-2-甲基-3-(三甲基硅氧基)-1,3-戊二烯置于吡啶,咪唑,2,6-二甲基吡啶,4-二甲氨基吡啶,N-碘代丁二酰亚胺,Lithium Aluminium Tetrahydride,草酰氯,偶氮二异丁腈,Camphor-10-Sulfonic Acid,Diethylzinc,三正丁基氢锡,二甲基二环氧乙烷,四氯化钛,Potassium Carbonate,戴斯-马丁氧化剂,对甲苯磺酸,氟化氢吡啶,二甲基亚砜,三乙胺,9-硼双环[3.3.1]壬烷,2,3-二氯-5,6-二氰基-1,4-苯醌,[双(三氟乙酰氧基)碘]苯,Lithium Diisopropyl Amide体系中,用 四氢呋喃,1,4-二氧六环,甲醇,乙醚,二氯甲烷,水,N,N-二甲基甲酰胺,丙酮,甲苯,苯 用作溶剂,化学反应 36.33H,反应生成西洛他唑
参考文献:Total Syntheses Of Epothilones A And B
标题:Total Syntheses Of Epothilones A And B
摘要: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 Nonenolizable 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.
Doi:10.1021/ja971946K

专利信息

专利号:US-2004018598-A1
优先权日:2000-05-30
标题 :Bio-intermediates for use in the chemical synthesis of polyketides
发明人：SANTI DANIEL; ASHLEY GARY; MYLES DAVID C
摘要:The present invention relates to compounds made by a subset of modules from one or more polyketide synthase (“PKSâ€?) genes that are used as starting material in the chemical synthesis of novel molecules, particularly naturally occurring polyketides or derivatives thereof. The biologically derived intermediates (“bio-intermediatesâ€?) generally represent particularly difficult compounds to synthesize using traditional chemical approaches due to one or more stereocenters. In one aspect of the invention, an intermediate in the synthesis of epothilone is provided that feeds into the synthetic protocol of Danishefsky and co-workers. In another aspect of the invention, intermediates in the synthesis of discodermolide are provided that feed into the synthetic protocol of Smith and co-workers. By taking advantage of the inherent stereochemical specificity of biological processes, the syntheses of key intermediates and thus the overall syntheses of compounds like epothilone and discodermolide are greaty simplified.

专利号:WO-2005054429-A3
优先权日:2003-11-19
标 题:Synthesis of the c1-c6 keto-acid synthon of the epothilones
发明人：AVERY MITCHELL A; ZHENG YANSONG
权利人:UNIV MISSISSIPPI; AVERY MITCHELL A; ZHENG YANSONG
摘要:The present invention relates to alternative methods for producing keto-acid synthons, which are useful for the synthesis of epothilones and analogs and derivatives thereof. A general method according to the present invention broadly comprises performing aldol condensation of a first aldehyde of a general formula: (I) with a carbonyl compound in the form of a ketone or a second aldehyde having a generalized formula: (II) thereby to form a first compound having a generalized formula : (III) and thereafter converting the first compound to a protected keto-`acid synthon of generalized formula: (IV) The present invention is also directed to chemical compounds useful in the synthesis of epothilones and analogs and derivatives thereof and to methods for forming each of these chemical compounds.

专利号:US-6350878-B1
优先权日:1998-05-18
标 题 :Intermediates for the synthesis of epothilones and methods for their preparation
发明人：ALTMANN KARL-HEINZ; BAUER ARMIN; SCHINZER DIETER
权利人:NOVARTIS AG
摘要:The invention relates to a method of synthesis for a compound of formula (I),wherein R is a heterocyclyl moiety and X1, X2, X3 and X4 are, independently of each other, protecting groups, which is appropriate for the synthesis of epothilone B and desoxyepothione B.

专利号:US-2007015260-A1
优先权日:2002-03-14
标 题:Synthesis of synthons for the manufacture of bioactive compounds
发明人：WONG CHI-HUEY; LIU JUNJIE; DESANTIS GRACE; BURK MARK
权利人:SCRIPPS RESEARCH INST
摘要:The present invention is based on the discovery that 2-deoxyribose-5-phosphate aldolase (DERA, EC 4.1.2.4) and variants thereof can be used to catalyze sequential asymmetric aldol reactions between a wide variety of donor and acceptor aldehydes. The reaction products typically contain at least two new stereogenic centers and can be produced in enantiomerically pure form. As such, DERA catalyzed asymmetric aldol chemistry can be exploited to produce synthons for the synthesis of a variety of bioactive molecules.

专利号:US-6933385-B2
优先权日:2001-08-03
标题 :Protected 3,5-dihydroxy-2,2-dimethyl-valeroamides for the synthesis of epothilones and derivatives and process for the production and the use
发明人：WESTERMANN JURGEN; PLATZEK JOHANNES; PETROV ORLIN
权利人:SCHERING AG
摘要:The invention relates to new protected 3,5-dihydroxy-2,2-dimethyl-valeroamides for the synthesis of epothilones and derivatives and process for the production and the use of the new compounds for the production of epothilones or epothilone derivatives.

专利号:US-6603015-B2
优先权日:1999-03-29
标题:Synthesis of epothilones
发明人：GEORG GUNDA I; NAIR SAJIV K; REIFF EMILY; TUNOORI ASHOK RAO
权利人:UNIV KANSAS
摘要:Commercially feasible methods for synthesizing various epothilones precursors needed for the preparation of final epothilones are provided, including techniques for the synthesis of epothilone segment A and C precursors. Segment C precursors are prepared using starting nitriles, which can alternately be oxidized to ketones and converted, or reacted to form the diol with subsequent conversion to the segment. Segment A precursors are prepared by reacting a starting enone with a chiral catalyst to give an intermediate alcohol in high enantomeric excess, followed by conversion of the alcohol to the desired Segment A precursor.