3β,20,25-trihydroxy-(20R)-26,27-bisnorcholest-5-en-22-one 3-(2'-tetrahydropyranyl) ether | 136634-04-3

• 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: 3β,20,25-trihydroxy-(20R)-26,27-bisnorcholest-5-en-22-one 3-(2'-tetrahydropyranyl) ether
• 英文别名: (20R)-26,27-bisnorcholest-5-en-22-one-3β,20,25-triol 3-(2'-tetrahydropyranyl) ether；(2R)-2-[(3S,8S,9S,10R,13S,14S,17S)-10,13-dimethyl-3-(oxan-2-yloxy)-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2,6-dihydroxyhexan-3-one
• CAS: 136634-04-3
• 化学式: C₃₀H₄₈O₅
• 分子量: 488.708
• InChiKey: ANCPGWUPFPTLMR-GHUBMNBKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3β,20,25-trihydroxy-(20R)-26,27-bisnorcholest-5-en-22-one 3-(2'-tetrahydropyranyl) ether 在 盐酸 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 (20R)-26,27-bisnorcholest-5-en-22-one-3β,20,25-triol
  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：

  2,3-二氢呋喃 、 3β-<(tetrahydro-2H-pyran-2-yl)oxy>-5-pregnen-20-one 在 叔丁基锂 作用下， 生成 (20S)-26,27-bisnorcholest-5-en-22-one-3β,20,25-triol 3-(2'-tetrahydropyranyl) ether 、 3β,20,25-trihydroxy-(20R)-26,27-bisnorcholest-5-en-22-one 3-(2'-tetrahydropyranyl) ether
  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

• Novel synthesis of cholesterol analogs: condensation of pregnenolone with dihydropyran or dihydrofuran
  作者：Zsuzsa Szendi、Frederick Sweet

  DOI：10.1016/0039-128x(91)90001-c

  日期：1991.9

  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.