(aS,1R,3R,7E)-9,10-seco-19-norcholesta-5,7-diene-1,2,3,25-tetraol

• 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: (aS,1R,3R,7E)-9,10-seco-19-norcholesta-5,7-diene-1,2,3,25-tetraol
• 英文别名: 1α,2α,25-trihydroxy-19-nor-vitamin D3；1α,2α,25-trihydroxy-19-norvitamin D3；1α,2α,25-(OH)3-19-nor-D3
• 化学式: C₂₆H₄₄O₄
• 分子量: 420.633
• InChiKey: CAGYDFRJDSWOLS-YUAOTPKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.51
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  80.92
• 氢给体数：
  4.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  (1R,3aR,7aR)-1-[(1R)-1,5-二甲基-5-[(三乙基硅烷基)氧基]己基]八氢-7a-甲基-4H-茚-4-酮 在 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 35.0h， 生成 (aS,1R,3R,7E)-9,10-seco-19-norcholesta-5,7-diene-1,2,3,25-tetraol
  参考文献：
  名称：

  Synthesis and Biological Activity of 2-Hydroxy and 2-Alkoxy Analogs of 1.alpha.,25-Dihydroxy-19-norvitamin D3

  摘要：

  1 alpha,2 alpha,25 Trihydroxy-19-norvitamin D-3, 1 alpha,2 beta,25-trihydroxy-19-norvitamin D-3, and their alkoxy analogs were efficiently prepared in a convergent synthesis, starting with (-)-quinic acid and a Windaus-Grundmann type ketone. Configurations of the A-ring fragment substituents were determined by H-1,H-1 COSY 2D spectra and H-1 NOE difference spectroscopy. The new analogs exhibited selective activity in stimulating intestinal calcium transport while having little or no activity in mobilizing bone calcium. They also showed HL-60-differentiating activity equal to or 10 times lower than that of 1 alpha,25-dihydroxyvitamin D-3.

  DOI：

  10.1021/jm00048a009

文献信息

• Efficient Synthesis of 2-Modified 1α,25-Dihydroxy-19-norvitamin D₃ with Julia Olefination:  High Potency in Induction of Differentiation on HL-60 Cells
  作者：Keiichiro Ono、Akihiro Yoshida、Nozomi Saito、Toshie Fujishima、Shinobu Honzawa、Yoshitomo Suhara、Seishi Kishimoto、Takayuki Sugiura、Keizo Waku、Hiroaki Takayama、Atsushi Kittaka

  DOI：10.1021/jo034787y

  日期：2003.9.1

  Six novel 2-substituted analogues of 1alpha,25-dihydroxy-19-norvitamin D(3), 6a,b-8a,b, were efficiently synthesized utilizing (-)-quinic acid as the A-ring precursor. The C2-modified A-rings were prepared as 4-alkylated (3R,5R)-3,5-dihydroxycyclohexanones 12-15 from (-)-quinic acid based on radical allylation at the C4 position of methyl (-)-quinicate. The new type of the CD-ring coupling partner

  利用（-）奎尼酸作为A环前体有效合成了1alpha，25-dihydroxy-19-norvitamin D（3），6a，b-8a，b的六个新颖的2-取代类似物。基于在（-）-奎宁酸甲酯的C 4位上的自由基烯丙基化，由（-）-奎宁酸将C 2修饰的A-环制备为4-烷基化的（3R，5R）-3，5-二羟基环己酮12-15。由25-羟基Grundmann's酮19合成了新型的CD-环偶联配偶体23，以应用于改性的Julia烯化反应，以在A-环和CD-环之间构建一个二烯单元。包括脱保护步骤在内的偶联产率为47-62％。根据C2立体化学分离了非对映异构体后，通过（1）H NMR实验确定了结构（2alpha或2beta），并将其与DeLuca的2-甲基-和2-乙基-1alpha进行了比较，25-二羟基-19-norvitamin D（3）。因此，合成的2alpha-（3-羟丙基）-1alpha，25-d
• Synthesis, Conformational Analysis, and Biological Evaluation of 19-<i>nor</i>-Vitamin D₃ Analogues with A-Ring Modifications
  作者：Laura Sánchez-Abella、Susana Fernández、Annemieke Verstuyf、Lieve Verlinden、Vicente Gotor、Miguel Ferrero

  DOI：10.1021/jm900711d

  日期：2009.10.8

  We have synthesized several isomers of 19-nor-vitamin D analogues possessing a hydroxy group at C-2 as well as novel derivatives bearing an epoxy substituent at the A-ring. All vitamins were prepared in convergent syntheses utilizing the modified Julia olefination. 1α,2α,25-Trihydroxy-19-nor-vitamin D3 (3) and 2β,3β-epoxy-1α,25-dihydroxy-3-deoxy-19-nor-vitamin D3 (10), which showed the highest affinity

  我们已经合成了在C-2处具有羟基的19-或-维生素D类似物的几种异构体，以及在A环上带有环氧取代基的新型衍生物。所有的维生素都是利用聚变的朱莉娅烯化反应以收敛合成的方式制备的。1α，2α，25-三羟基-19-或-维生素D 3（3）和2β，3β-环氧-1α，25-二羟基-3-脱氧-19-或-维生素D 3（10），显示最高对维生素D受体的亲和力，在测试的化合物中表现出最高的抑制MCF-7乳腺癌细胞增殖的潜能。
• Novel synthesis of 2-Substituted 19-norvitamin D A-ring phosphine oxide from d-glucose as a building block
  作者：Masato Shimizu、Yukiko Iwasaki、Yoshinori Shibamoto、Miki Sato、H.F DeLuca、Sachiko Yamada

  DOI：10.1016/s0960-894x(03)00005-2

  日期：2003.3

  19-Norvitamin D A-ring phosphine oxide 5 was synthesized by a new sequence mode starting from D-glucose as a chiral template. Transformation of the pyranoside ring into the A-ring carbocycle was achieved by the Pd-catalyzed Ferrier rearrangement. The phosphine oxide 5 was obtained in an 18% overall yield by this novel cost-effective method. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Synthesis and Biological Activity of 2-Hydroxy and 2-Alkoxy Analogs of 1.alpha.,25-Dihydroxy-19-norvitamin D3
  作者：Rafal R. Sicinski、Kato L. Perlman、Hector F. DeLuca

  DOI：10.1021/jm00048a009

  日期：1994.10

  1 alpha,2 alpha,25 Trihydroxy-19-norvitamin D-3, 1 alpha,2 beta,25-trihydroxy-19-norvitamin D-3, and their alkoxy analogs were efficiently prepared in a convergent synthesis, starting with (-)-quinic acid and a Windaus-Grundmann type ketone. Configurations of the A-ring fragment substituents were determined by H-1,H-1 COSY 2D spectra and H-1 NOE difference spectroscopy. The new analogs exhibited selective activity in stimulating intestinal calcium transport while having little or no activity in mobilizing bone calcium. They also showed HL-60-differentiating activity equal to or 10 times lower than that of 1 alpha,25-dihydroxyvitamin D-3.