(20R)-<6'-(3',4'-<2'H>-dihydropyranyl)>pregn-5-ene-3β,20-diol 3-acetate | 136634-00-9

• 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: (20R)-<6'-(3',4'-<2'H>-dihydropyranyl)>pregn-5-ene-3β,20-diol 3-acetate
• 英文别名: (20R)-[6'-(3',4'-[2'H]dihydropyranyl)]-pregn-5-nen-3β,20-diol-3-acetate；[(3S,8S,9S,10R,13S,14S,17S)-17-[(1R)-1-(3,4-dihydro-2H-pyran-6-yl)-1-hydroxyethyl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
• CAS: 136634-00-9
• 化学式: C₂₈H₄₂O₄
• 分子量: 442.639
• InChiKey: XRERZXHFNATBLL-FVXQNEOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (20R)-<6'-(3',4'-<2'H>-dihydropyranyl)>pregn-5-ene-3β,20-diol 3-acetate 在 盐酸 作用下， 生成 (20R)-27-norcholest-5-en-22-one-3β,20,26-triol 3-acetate
  参考文献：
  名称：

  Novel synthesis of cholesterol analogs: condensation of pregnenolone with dihydropyran or dihydrofuran

  摘要：

  Pregnenolone 3-(2'-tetrahydropyranyl) ether (1) was condensed with 3,4-[H-2]dihydropyran to mainly give (20R)-[6'-(3',4'-[2'H]dihydropyranyl)]-pregn-5-ene-3-beta,20-diol 3-(2'-tetrahydropyranyl) ether (20R-3), according to nuclear magnetic resonance (NMR). Cold, dilute HCl in ethanol removed the tetrahydropyranyl group at C-3 and also opened the dihydropyranyl ring at the C-20 position of 20R-3 to give (20R)-27-norcholest-5-en-22-one-3-beta,20,26-triol (20R-5). Analogous results were obtained by condensing pregnenolone 3-acetate with 3,4-[H-2]dihydropyran to provide (20R)-[6'-(3',4'-[2'H]dihydropyranyl)]-pregn-5-ene-3-beta,20-diol 3-acetate (20R-4). Acid-catalyzed opening of the dihydropyranyl ring at C-20 in 20R-4 yielded 20R-7, which, on acetylation followed by crystallization, provided (20R)-27-norcholest-5-en-22-one-3-beta,20,26-triol 3,26-diacetate (20R-8), identical to the diacetate made from 20R-5. Varying the reaction sequence beginning with 20(R,S)-4 gave an 84:16 ratio of 20R to 20S in a mixture of 20(R,S)-8, according to NMR analysis. Crystallization of the mixture from methanol provided pure 20R-8. Condensing 2,3-dihydrofuran and 1 for producing (20R)-[5'-(2',3'-dihydrofuranyl)]-pregn-5-ene-3-beta,20-diol 3-(2'-tetrahydropyranyl) ether (6) gave instead (20R)-26,27-bisnorcholest-5-en-22-one-3-beta,20,25-triol 3-(2'-tetrahydropyranyl) ether (20R-9) by partial hydrolysis during workup. Treating 20R-9 briefly with dilute HCl produced (20R)-26,27-bisnorcholest-5-en-22-one-3-beta,20,25-triol (20R-10). Structural assignments for the new steroids are supported by NMR, mass spectroscopy, elemental analysis, and cleavage with HIO4 of the alpha-hydroxy ketone group (at C-20 and C-22) in 5, 7, 8, 9, and 10 to give pregenolone (or pregnenolone 3-acetate). Efficient condensation of pregnenolone with 3,4-[H-2]dihydropyran or 2,3-dihydrofuran provides a novel route to elaborating the side chain on the D ring, pointing the way to new syntheses of cholesterol analogs.

  DOI：

  10.1016/0039-128x(91)90001-c
• 作为产物：
  描述：

  孕烯醇酮醋酸酯 在 吡啶 、 叔丁基锂 作用下， 生成 (20R)-<6'-(3',4'-<2'H>-dihydropyranyl)>pregn-5-ene-3β,20-diol 3-acetate
  参考文献：
  名称：

  Novel synthesis of cholesterol analogs: condensation of pregnenolone with dihydropyran or dihydrofuran

  摘要：

  Pregnenolone 3-(2'-tetrahydropyranyl) ether (1) was condensed with 3,4-[H-2]dihydropyran to mainly give (20R)-[6'-(3',4'-[2'H]dihydropyranyl)]-pregn-5-ene-3-beta,20-diol 3-(2'-tetrahydropyranyl) ether (20R-3), according to nuclear magnetic resonance (NMR). Cold, dilute HCl in ethanol removed the tetrahydropyranyl group at C-3 and also opened the dihydropyranyl ring at the C-20 position of 20R-3 to give (20R)-27-norcholest-5-en-22-one-3-beta,20,26-triol (20R-5). Analogous results were obtained by condensing pregnenolone 3-acetate with 3,4-[H-2]dihydropyran to provide (20R)-[6'-(3',4'-[2'H]dihydropyranyl)]-pregn-5-ene-3-beta,20-diol 3-acetate (20R-4). Acid-catalyzed opening of the dihydropyranyl ring at C-20 in 20R-4 yielded 20R-7, which, on acetylation followed by crystallization, provided (20R)-27-norcholest-5-en-22-one-3-beta,20,26-triol 3,26-diacetate (20R-8), identical to the diacetate made from 20R-5. Varying the reaction sequence beginning with 20(R,S)-4 gave an 84:16 ratio of 20R to 20S in a mixture of 20(R,S)-8, according to NMR analysis. Crystallization of the mixture from methanol provided pure 20R-8. Condensing 2,3-dihydrofuran and 1 for producing (20R)-[5'-(2',3'-dihydrofuranyl)]-pregn-5-ene-3-beta,20-diol 3-(2'-tetrahydropyranyl) ether (6) gave instead (20R)-26,27-bisnorcholest-5-en-22-one-3-beta,20,25-triol 3-(2'-tetrahydropyranyl) ether (20R-9) by partial hydrolysis during workup. Treating 20R-9 briefly with dilute HCl produced (20R)-26,27-bisnorcholest-5-en-22-one-3-beta,20,25-triol (20R-10). Structural assignments for the new steroids are supported by NMR, mass spectroscopy, elemental analysis, and cleavage with HIO4 of the alpha-hydroxy ketone group (at C-20 and C-22) in 5, 7, 8, 9, and 10 to give pregenolone (or pregnenolone 3-acetate). Efficient condensation of pregnenolone with 3,4-[H-2]dihydropyran or 2,3-dihydrofuran provides a novel route to elaborating the side chain on the D ring, pointing the way to new syntheses of cholesterol analogs.

  DOI：

  10.1016/0039-128x(91)90001-c

文献信息

• Stereoselective reactions of (20R)-3,20-dihydroxy-(3′,4′-dihydro-2′H-pyranyl)-5-pregnene derivatives form 27-nor-3,20,23,26-tetrahydroxy-cholesten-22-ones and related bromo ketones
  作者：Angéla Magyar、Zsuzsanna Szendi、Péter Forgó、Marianna Mák、Helmar Görls、Frederick Sweet

  DOI：10.1016/j.steroids.2003.09.011

  日期：2004.1

  20-dihydroxy-(3',4'-dihydro-2'H-pyranyl)-5-pregnene (4) giving mostly (20R,23R)-23-bromo-3,20,26-trihydroxy-27-norcholest-5-en-22-one (7a). Thus both major steroidal products 2a and 7a have the same C-23R configuration. Assignment of molecular structures and the absolute configurations to 1 and 2a were based on elemental analysis, mass spectra, nuclear magnetic resonance, FTIR infrared spectroscopic

  先前报道的孕烯醇酮类似物具有通过 Cz.sbnd;C 键连接到 C-20 位置 (1) 的 3,4-二氢-2H-吡喃，在 -5 摄氏度下与甲醇中的间氯过苯甲酸立体选择性反应. 分离的中间体的酸催化水解产生了大部分新的 27-norcholesterol 类似物的良好产率：(20R,23R)-3,20,23,26-tetrahydroxy-27-norcholest-5-en-22-one-3 -乙酸酯（2a，以及少量的 23S 对映异构体 2b）。环氧化和甲醇分解后进行酸催化水解的三种不同条件通常会产生大约 2:1 的 23R:23S 非对映异构体，在新的不对称中心具有一个 C-23 羟基。溴还与 (20R)-3,20-二羟基-(3',4'-二氢-2'H-吡喃基)-5-孕烯 (4) 发生立体选择性反应，主要生成 (20R,23R)-23-溴-3 ,20, 26-trihydroxy-27-