CAS: 152044-54-7; (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12,16-Pentamethyl-3-((E)-1-(2-Methylthiazol-4-yl)Prop-1-En-2-yl)-4,17-Dioxabicyclo[14.1.0]Heptadecane-5,9-Dione

上下游产品

epothilone D (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-16-iodomethyl-8,8,10,12-tetramethyl-3-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione (1S,3S,7S,10R,11S,12S,16R)-7-(tert-Butyl-dimethyl-silanyloxy)-11-hydroxy-8,8,10,12,16-pentamethyl-3-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-4,17-dioxa-bicyclo[14.1.0]heptadecane-5,9-dione (E)-9,10-dehydroepothilone Bepothilone D (4S,7R,8S,9S,13Z,16S,1'E)-4,8-di-tert-butyldimethylsilyloxy-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)-1-ethenyl]-1-oxa-13-cyclohexadecene-2,6-dione (1S,3S,7S,10R,11S,12S,16S)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4-oxabicyclo[14.1.0]heptadecane-5,9-dione Epothilone F

(E)-9,10-Dehydro-12,13-Desoxyepothilone B置于trisnhnh2,二甲基二环氧乙烷,三乙胺体系中,用 二氯甲烷,1,2-二氯乙烷,丙酮 用作溶剂,化学反应 8.7H,反应生成埃博霉素b
参考文献:通过化学合成发现 (E)-9,10-脱氢埃坡霉素:关于 26-三氟-(E)-9,10-脱氢-12,13-脱氧埃坡霉素 B 作为有前景的抗癌候选药物的出现
标题:通过化学合成发现 (E)-9,10-脱氢埃坡霉素:关于 26-三氟-(E)-9,10-脱氢-12,13-脱氧埃坡霉素 B 作为有前景的抗癌候选药物的出现
摘要:我们全面介绍了 12,13-脱氧埃坡霉素 B (Depob) 的 (E)-9,10-脱氢衍生物的发现,这是一类具有非常好体内临床前特性的新型抗肿瘤药物.迄今为止,无法通过修饰任何天然存在的埃坡霉素获得的化合物是通过全化学合成发现的.我们描述了我们对埃坡霉素设置中的闭环复分解反应的研究如何导致 (E)-9,10-脱氢-12,13-脱氧埃坡霉素同源物 6 的第一代和第二代合成.经过进一步修改,该合成应用于达到 26-三氟衍生化合物(见化合物 7).为了进行此类研究并预期未来的发展需求,导致最初发现化合物 7 的全合成被显着简化.然后应用用于获得化合物 7 的全合成方法获得更容易配制的化合物,在 21 位带有羟基和氨基官能团(参见化合物 45,62 和 63).在对这些新同源物进行广泛的体外评估后,化合物 7 被提名用于异种移植模型的体内评估.本文提供的数据证明了有希望的治疗功效,对大肿瘤的活性,
Doi:10.1021/ja046992G

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:US-12383499-B2
优先权日:2018-01-01
标题:Scale up synthesis of silicasome nanocarriers
发明人：NEL ANDRE E; MENG HUAN; LIU XIANGSHENG
权利人:UNIV CALIFORNIA
摘要:In order to facilitate the approval and commercialization of silicasome drug delivery systems (e.g. irinotecan silicasomes) it is necessary to scale up synthesis of the drug-loaded silicasomes. In this regard, it was discovered that the synthesis protocols used for laboratory synthesis of drug-loaded silicasomes (e.g., 500 mg/batch) do not scale to large scale silicasome production, because the resulting products were too heterogeneous for use as pharmaceuticals. Accordingly, new methods are provided herein that effectively afford the large-scale production of mesoporous silica nanoparticles (MSNPs) and lipid bilayer coated MSNPs (silicasomes).

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-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.

专利号:US-7321046-B2
优先权日:2002-09-06
标 题 :Analogs of dictyostatin, intermediates therefor and methods of synthesis thereof
发明人：CURRAN DENNIS P; SHIN YOUSEUNG; FOURNIER JEAN-HUGUES; MANCUSO JOHN; DAY BILLY W; BRUCKNER ARNDT; FUKUI YOSHIKAZU
权利人:UNIV PITTSBURGH
摘要:Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer n nwherein R 1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R 2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e ; R a , R b and R c are independently an alkyl group or an aryl group; R d is an alkyl group, an aryl group, an alkoxylalkyl group, —R i SiR a R b R c or a benzyl group, wherein R i is an alkylene group; R e is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NR g R h , wherein R g and R h are independently H, an alkyl group or an aryl group; R 3 is (CH 2 ) n where n is and integer in the range of 0 to 5, —CH 2 CH(CH 3 )—, —CHâ•?CH—, —CHâ•?C(CH 3 )—, or —C≡C—; R 4 isn n nwherein R 23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e ; R 23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e , or R 23a and R 23b together form a portion of six-membered acetal ring incorporating CR t R u ; R t and R u are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R 5 is H or OR 2b , wherein R 2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiR a R b R c , CH 2 OR d , or COR e ; provided that the compound is not dictyostatin 1.

专利号:US-2017283878-A1
优先权日:2015-12-11
标题:Modulation of globoseries glycosphingolipid synthesis and cancer biomarkers
发明人：WONG CHI-HUEY; WU CHUNG-YI; CHEUNG SARAH K C; CHUANG PO-KAI; HSU TSUI-LING
权利人:ACADEMIA SINICA
摘要:The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for diagnostic and therapeutic uses.