[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1-Hydroxy-19,30-Dimethoxy-15,17,21,23,29,35-Hexamethyl-2,3,10,14,20-Pentaoxo-18-Triethylsilyloxy-11,36-Dioxa-4-Azatricyclo[30.3.1.04,9]Hexatriaconta-16,24,26,28-Tetraen-12-Yl]Propyl]-2-Methoxycyclohexyl] 2,2,5-Trimethyl-1,3-Dioxane-5-Carboxylate置于硫酸体系中,用 四氢呋喃,水 用作溶剂,化学反应 50.5H,以77.1%的收率获得西罗莫司脂化物 参考文献:Process For Preparation Of Temsirolimus 标题:Process For Preparation Of Temsirolimus 摘要:该发明提供了两种合成通向替西罗莫司(化合物1B和替西罗莫司类似物1A)的方法.第一种方法包括通过在有机碱存在下,直接将雷帕霉素(4B)或脯氨酰-雷帕霉素(4A)与取代基-2,2-双(甲氧基)丙酸酐(11)反应,然后去保护基得到cci-779或脯氨酰cci-779的合成.第二种方法包括涉及雷帕霉素-Oh-31-硅醚(4D)或脯氨酰-雷帕霉素-Oh-31-硅醚(4C)与取代基-2,2-双(甲氧基)丙酸酐(11)在有机碱存在下反应,然后经过随后的水解步骤得到所需的cci-779或脯氨酰cci-779. 如本发明所述,化合物11在室温下稳定,成本效益高且易于加工.
专利信息
专利号:US-7202256-B2 优先权日:2004-04-14 标题:Proline CCI-779, production of and uses therefor, and two-step enzymatic synthesis of proline CCI-779 and CCI-779 发明人:GU JIANXIN; RUPPEN MARK E; RAVEENDRANATH PANOLIL; CHEW WARREN; SHAW CHIA-CHENG 权利人:WYETH CORP 摘要:Methods for the synthesis of CCI-779 and proline-CCI-779 are described, including a method involving lipase-catalyzed acetylation of 42-hydroxy of rapamycin with a vinyl ester of 2,2-bis(hydroxymethyl) propionic acid in an organic solvent followed by deprotection. Also provided are products containing proline-CCI-779 and uses thereof.
专利号:US-7268144-B2 优先权日:2004-04-14 标 题 :Regiospecific synthesis of rapamycin 42-ester derivatives 发明人:GU JIANXIN; CAI PING; RUPPEN MARK E 权利人:WYETH CORP 摘要:A method for the regiospecific synthesis of rapamycin 42-ester derivatives is described. The method involves lipase-catalyzed acetylation of 42-hydroxy of rapamycin with an acyl donor such as a vinyl ester, an isopropenyl ester or an anhydride in a suitable organic solvent.
专利号:US-8258299-B2 优先权日:2009-03-27 标题:Process for preparation of temsirolimus 发明人:LEE KWANG-CHUNG; LEE TING-HUEI; TUNG YEN-SHIH; KAO CHIA-CHEN; LEE TZU-AI 权利人:LEE KWANG-CHUNG; LEE TING-HUEI; TUNG YEN-SHIH; KAO CHIA-CHEN; LEE TZU-AI; CHUNGWA CHEMICAL SYNTHESIS & BIOTECH CO LTD 摘要:The present invention provides two synthetic routes for the preparation of Temsirolimus (compound 1b and analog of Temsirolimus 1a). The first route includes the synthesis of CCI-779 by directly reacting rapamycin (4b) or Prolyl-rapamycin (4a) with substituent-2,2-bis(methoxy) propionic acid anhydride(11) in the presence of an organic base, followed by deprotection to give CCI-779 or Proline CCI-779. The second route includes a process involving a reaction of rapamycin-OH-31-sily ether (4d) or Prolyl-rapamycin-OH-31-sily ether (4c) with substituent-2,2-bis(methoxy) propionic acid anhydride(11) in the presence of an organic base and followed by subsequent hydrolysis step to obtain the desired CCI-779 or Proline CCI-779. n Compound 11, as described in this invention, is stable at room temperature, cost effective and ease of processing.
专利号:US-10973847-B2 优先权日:2017-06-30 标题 :Core-to-surface polymerization for the synthesis of star polymers and uses thereof 发明人:JOHNSON JEREMIAH A; GOLDER MATTHEW R 权利人:MASSACHUSETTS INST TECHNOLOGY 摘要:Disclosed are methods, compositions, reagents, systems, and kits to prepare star polymers, as well as compositions and uses thereof. Various embodiments show that synthesis of these polymers contain low metal concentration to provide polymers for diverse biomedical applications including in vivo applications.
专利号:US-2021220331-A1 优先权日:2016-05-03 标题:Inhibitors of ires-mediated protein synthesis 发明人:GERA JOSEPH F; LICHTENSTEIN ALAN; JUNG MICHAEL E; LEE JIHYE; HOLMES BRENT; BENAVIDES-SERRATO ANGELICA 权利人:UNIV CALIFORNIA; THE UNITED STATE GOVERNMENT REPRESENTED BY THE DEPT OF VETERANS AFFAIRS 摘要:This disclosure relates to inhibitors of IRES-mediated protein synthesis, compositions comprising therapeutically effective amounts of these compounds, and methods of using those compounds and compositions in treating hyperproliferative disorders, e.g., cancers. This disclosure also relates to compositions comprising inhibitors of IRES-mediated protein synthesis and mTOR inhibitors, and to methods of treating cancer by conjoint administration of inhibitors of IRES-mediated protein synthesis and mTOR inhibitors.
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.
1: Houeis L, van der Plancke G, Cacciottola L, Goudmaeker A, Kluyskens C, Zipponi M, Dehoux JP, Donnez J, Dolmans MM. Temsirolimus and antimüllerian hormone protect fertility and the ovarian reserve against chemotherapy-induced damage in a murine model. Fertil Steril. 2025 Jul 23:S0015-0282(25)00603-X. doi: 10.1016/j.fertnstert.2025.07.030. Epub ahead of print. 8(2):184-190. doi: 10.36401/JIPO-25-3. 4: Stitzlein LM, Baig MU, Chandra J, McGovern S, Paulino A, Ketonen LM, Khatua S, Zaky W. Phase I Study of Vorinostat and Temsirolimus in Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma. Pediatr Blood Cancer. 2025 May;72(5):e31619. doi: 10.1002/pbc.31619. Epub 2025 Feb 25.
合成参考文献
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