11α-O-(tert-butyl-dimethylsilanyloxy)pregn-4-en-3,20-dione | 1312468-50-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 11α-O-(tert-butyl-dimethylsilanyloxy)pregn-4-en-3,20-dione
• 英文别名: 17-acetyl-11-(tert-butyldimethylsilanyloxy)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one；11α-(tert-butyldimethylsilanyloxy)pregn-4-ene-3,20-dione；11alpha-(tert-Butyl-dimethyl-silanyloxy)pregn-4-en-3,20-dione；(8S,9S,10R,11R,13S,14S,17S)-17-acetyl-11-[tert-butyl(dimethyl)silyl]oxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
• CAS: 1312468-50-0
• 化学式: C₂₇H₄₄O₃Si
• 分子量: 444.73
• InChiKey: WUNBPQISHRAPCK-ZMEKTPQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.72
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  11α-O-(tert-butyl-dimethylsilanyloxy)pregn-4-en-3,20-dione 在 吡啶 、 sodium tetrahydroborate 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 3β,20-diacetoxy-4-pregnen-11α-ol
  参考文献：
  名称：

  Microwave assisted preparation of C(1)–C(11) oxygen-bridged pregnanes

  摘要：

  1,11-Epoxysteroids may be obtained by an intramolecular remote functionalization using Suarez reagent (diacetoxyiodobenzene/I-2) and irradiation with visible light. We have found that photolysis with visible light may be advantageously replaced by microwave irradiation to prepare 1,11-oxygen bridges resulting in higher yields and shorter reaction times especially in the case of sensitive substrates. Both methodologies were compared on a set of representative 11-alpha-hydroxypregnanes (3, 8, 10 and 11). (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.07.016
• 作为产物：
  描述：

  11Alpha-孕酮 、 叔丁基二甲基氯硅烷 以 氯仿 为溶剂， 反应 72.0h， 以87%的产率得到11α-O-(tert-butyl-dimethylsilanyloxy)pregn-4-en-3,20-dione
  参考文献：
  名称：

  使用某些化学工具设计和合成四种类固醇-环氧乙烷衍生物。

  摘要：

  这项研究涉及几种新的孕酮，11a-羟基孕酮，11a-叔丁基二甲基硅烷基氧基孕酮和雄激素的衍生物的合成。通过将四种甾族化合物的4-en-3-one部分与2-羟基-1-萘醛缩合，得到一系列的4-（R）-羟基-（2-羟基萘基-1-基）来制备新的衍生物。 ）加合物。这些加合物通过二羟基萘基部分与琥珀酸的环化反应进一步改性，然后将所得的环状琥珀酸酯与乙二胺缩合以形成所有可用羰基上的亚胺衍生物。然后通过用氯乙酰氯对11-和17-亚胺氮进行N-酰化来衍生化这些化合物，然后将所得的氯乙酰胺与2-羟基-1-萘乙醛在Darzens型反应中缩合，从而在侧链中形成相应的环氧乙酰胺。另外，通过NMR光谱数据证实了类固醇衍生物的化学结构。

  DOI：

  10.1016/j.steroids.2016.04.012

文献信息

• [EN] NEW STEROID INHIBITORS OF PGP FOR USE FOR INHIBITING MULTIDRUG RESISTANCE<br/>[FR] NOUVEAUX INHIBITEURS STÉROÏDIENS DE PGP POUR EMPLOI DANS L'INHIBITION DE LA RÉSISTANCE PLÉIOTROPE
  申请人：INST NAT SANTE RECH MED

  公开号：WO2011073419A1

  公开（公告）日：2011-06-23

  The present invention relates to a compound of formula (I) for its use for reversing or inhibiting multidrug resistance.

  本发明涉及一种化合物，其化学式为(I)，用于逆转或抑制多药耐药。
• NEW STEROID INHIBITORS OF PGP FOR USE FOR INHIBITING MULTIDRUG RESISTANCE
  申请人：Grenot Catherine

  公开号：US20120309728A1

  公开（公告）日：2012-12-06

  The present invention relates to a compound of formula (I) for its use for reversing or inhibiting multidrug resistance.

  本发明涉及一种式（I）的化合物，用于逆转或抑制多药耐药。
• Synthesis of New Steroidal Inhibitors of P-Glycoprotein-Mediated Multidrug Resistance and Biological Evaluation on K562/R7 Erythroleukemia Cells
  作者：Marc Rolland de Ravel、Ghina Alameh、Maxime Melikian、Zahia Mahiout、Agnès Emptoz-Bonneton、Eva-Laure Matera、Thierry Lomberget、Roland Barret、Luc Rocheblave、Nadia Walchshofer、Sonia Beltran、Lucienne El Jawad、Elisabeth Mappus、Catherine Grenot、Michel Pugeat、Charles Dumontet、Marc Le Borgne、Claude Yves Cuilleron

  DOI：10.1021/jm501676v

  日期：2015.2.26

  A simple route for improving the potency of progesterone as a modulator of P-gp-mediated multidrug resistance was established by esterification or etherification of hydroxylated 5 alpha/beta-pregnane-3,20-dione or 5 beta-cholan-3-one precursors. X-ray crystallography of representative 7 alpha-, 11 alpha-, and 17 alpha-(2'R/S)-O-tetrahydropyranyl ether diastereoisomers revealed different combinations of axial-equatorial configurations of the anomeric oxygen. Substantial stimulation of accumulation and chemosensitization was observed on K562/R7 erythroleukemia cells resistant to doxorubicin, especially using 7 alpha,11 alpha-O-disubstituted derivatives of 5 alpha/beta-pregnane-3,20-dione, among which the 5 beta-H-7 alpha-benzoyloxy-11 alpha-(2'R)-O-tetrahydropyranyl ether 22a revealed promising properties (accumulation index 2.9, IC50 0.5 mu M versus 1.2 and 10.6 mu M for progesterone), slightly overcoming those of verapamil and cyclosporin A. Several 7 alpha,12 alpha-O-disubstituted derivatives of 5 beta-cholan-3-one proved even more active, especially the 7 alpha-O-methoxymethyl-12 alpha-benzoate 56 (accumulation index 3.8, IC50 0.2 mu M). The panel of modulating effects from different O-substitutions at a same position suggests a structural influence of the substituent completing a simple protection against stimulating effects of hydroxyl groups on P-gp-mediated transport.
• Design and synthesis of four steroid-oxirane derivatives using some chemical tools
  作者：Figueroa-Valverde Lauro、Díaz-Cedillo Francisco、Ortega-Morales Otto、García-Cervera Elodia、Rosas-Nexticapa Marcela、Pool-Gómez Eduardo、Lopéz-Ramos Maria、Rodriguez-Hurtado Fernanda、Chan-Salvador Marissa

  DOI：10.1016/j.steroids.2016.04.012

  日期：2016.8

  This study involved the synthesis of several new derivatives of progesterone, 11a-hydroxyprogesterone, 11a-t-butyldimethylsilanyloxyprogesterone, and andrenosterone. The new derivatives were prepared by condensation of the 4-en-3-one moiety of the four steroids with 2-hydroxy-1-naphthaldehyde to afford a series of 4-(R)-hydroxy-(2-hydroxynaphtalen-1-yl) adducts. These adducts were further modified

  这项研究涉及几种新的孕酮，11a-羟基孕酮，11a-叔丁基二甲基硅烷基氧基孕酮和雄激素的衍生物的合成。通过将四种甾族化合物的4-en-3-one部分与2-羟基-1-萘醛缩合，得到一系列的4-（R）-羟基-（2-羟基萘基-1-基）来制备新的衍生物。 ）加合物。这些加合物通过二羟基萘基部分与琥珀酸的环化反应进一步改性，然后将所得的环状琥珀酸酯与乙二胺缩合以形成所有可用羰基上的亚胺衍生物。然后通过用氯乙酰氯对11-和17-亚胺氮进行N-酰化来衍生化这些化合物，然后将所得的氯乙酰胺与2-羟基-1-萘乙醛在Darzens型反应中缩合，从而在侧链中形成相应的环氧乙酰胺。另外，通过NMR光谱数据证实了类固醇衍生物的化学结构。
• Microwave assisted preparation of C(1)–C(11) oxygen-bridged pregnanes
  作者：Lautaro D. Alvarez、Juan M. Sonego、Adriana S. Veleiro、Gerardo Burton

  DOI：10.1016/j.steroids.2011.07.016

  日期：2011.12

  1,11-Epoxysteroids may be obtained by an intramolecular remote functionalization using Suarez reagent (diacetoxyiodobenzene/I-2) and irradiation with visible light. We have found that photolysis with visible light may be advantageously replaced by microwave irradiation to prepare 1,11-oxygen bridges resulting in higher yields and shorter reaction times especially in the case of sensitive substrates. Both methodologies were compared on a set of representative 11-alpha-hydroxypregnanes (3, 8, 10 and 11). (C) 2011 Elsevier Inc. All rights reserved.