(1R,3aR,4S,7aR)-7a-methyl-1-[(1S)-1-methyl-1-(phenylsulfonyl)ethyl]octahydro-1H-inden-4-ol | 239100-21-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,3aR,4S,7aR)-7a-methyl-1-[(1S)-1-methyl-1-(phenylsulfonyl)ethyl]octahydro-1H-inden-4-ol
• 英文别名: De-A,B-22-benzenesulphonyl-23,24-dinorcholestan-8-ol；(1R,3aR,4S,7aR)-1-[(2S)-1-(benzenesulfonyl)propan-2-yl]-7a-methyl-1,2,3,3a,4,5,6,7-octahydroinden-4-ol
• CAS: 239100-21-1
• 化学式: C₁₉H₂₈O₃S
• 分子量: 336.496
• InChiKey: ABCWTBVRNAKSES-GYFISPQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  62.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,3aR,4S,7aR)-7a-methyl-1-[(1S)-1-methyl-1-(phenylsulfonyl)ethyl]octahydro-1H-inden-4-ol 在 吡啶 、 4-二甲氨基吡啶 、 sodium amalgam 、 正丁基锂 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 33.0h， 生成 (1R,3aR,4S,7aR)-1-[(1R,4R)-4,5-dihydroxy-1,5-dimethylhexyl]-7a-methyl-octahydro-1H-inden-4-ol
  参考文献：
  名称：

  1alpha，24,25-三羟基-2β-（3-羟基丙氧基）维生素D（3）（24-羟基化ED-71）的合成和生物学表征。

  摘要：

  通过会聚方法以24（R）和24（S）形式合成24-羟基衍生物，作为与1α，25-二羟基-2β-（3-羟基丙氧基）维生素D（3）相关的类似物。在收敛性合成中，由D-酒石酸二乙酯合成的A环片段和24（R）和24（S）形式的C / D环片段（维生素D编号）从维生素D（2）获得通过Inhoffen-Lythgoe二醇，以中等收率偶联，得到1alpha，24（R），25-三羟基-2beta-（3-羟基丙氧基）维生素D（3）和1alpha，24（S），25-三羟基-2beta -（3-羟基丙氧基）维生素D（3）。在初步的生物学评估中，与母体化合物相比，1alpha，25-dihydroxy-2beta-（3-hydroxypropoxy）维生素D（3）的24-羟基化导致对维生素D结合蛋白的体外亲和力减弱，体内钙化活性降低。

  DOI：

  10.1016/s0039-128x(00)00149-5
• 作为产物：
  描述：

  (S)-2-((3R,3aR,7S,7aR)-octahydro-7-hydroxy-3a-methyl-1H-inden-3-yl)propyl 4-methylbenzenesulfonate 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 6.0h， 生成 (1R,3aR,4S,7aR)-7a-methyl-1-[(1S)-1-methyl-1-(phenylsulfonyl)ethyl]octahydro-1H-inden-4-ol
  参考文献：
  名称：

  Convergent Synthesis of 1α-Hydroxyvitamin D5

  摘要：

  An eleven-step. high-yielding (46%) synthesis of lu-hydroxyvitamin D-5 (2) Starting from vitamin D-2 (4) is described, in which a Julia olefination sequence is used for the construction of the (24R)-ethyl-substituted side chain.

  DOI：

  10.1002/1099-0690(200008)2000:15<2755::aid-ejoc2755>3.0.co;2-g

文献信息

• 24-HYDROXYVITAMIN D DERIVATIVES
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1061070A1

  公开（公告）日：2000-12-20

  Vitamin D derivatives having general formula (1) which are hydroxylated at the 24-position and considered as one of metabolites of physiologically active vitamin D derivatives substituted at the 2β-position wherein R1, R2, R3 and R4 are the same or different and each represents hydrogen or a protective group; X and Y represent each H or OR5, provided that Y is OR5 when X is H, and Y is H when X is OR5 (wherein R5 represents hydrogen or a protective group, or R1 and R5 may together form a vicinal-diol protective group); synthesis intermediates useful in synthesizing these vitamin D derivatives; and medicinal compositions containing these vitamin D derivatives.

  具有通式(1)的维生素 D 衍生物，该衍生物在 24 位羟基化，并被视为在 2β 位被取代的具有生理活性的维生素 D 衍生物的代谢产物之一，其中 R1、R2、R3 和 R4 相同或不同，且各自代表氢或保护基团；X和Y分别代表H或OR5，条件是当X为H时Y为OR5，而当X为OR5时Y为H（其中R5代表氢或保护基团，或R1和R5可共同形成一个沧海二醇保护基团）；用于合成这些维生素D衍生物的合成中间体；以及含有这些维生素D衍生物的药用组合物。
• 24-hydroxy vitamin D derivatives
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：US20020094972A1

  公开（公告）日：2002-07-18

  A process for preparing vitamin D derivatives having the following formula: 1 wherein R 1 , R 2 , R 3 , and R 4 , which may be the same or different, represent a hydrogen atom or a protecting group, comprising: reacting a compound of formula (2) 2 wherein R 1 represents a hydrogen atom or a protecting group, with a compound having the formula (3) 3 wherein R 1 represents a hydrogen atom and R 2 , R 3 , and R 4 , which are the same or different, represent a hydrogen atom or a protecting group.

  一种制备具有下式的维生素 D 衍生物的工艺： 1 其中 R 1 , R 2 , R 3 和 R 4 可以相同或不同，代表氢原子或保护基团，包括 使式 (2) 的化合物反应 2 其中 R 1 代表氢原子或保护基团，与式 (3) 3 其中 R 1 代表氢原子，R 2 , R 3 和 R 4 代表氢原子或保护基团。
• Synthesis of putative metabolites of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)
  作者：Yoshiyuki Ono、Hiroyoshi Watanabe、Ikuo Taira、Keisuke Takahashi、Jun Ishihara、Susumi Hatakeyama、Noboru Kubodera

  DOI：10.1016/j.steroids.2005.11.001

  日期：2006.7

  1 alpha,25-Dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (ED-71), an analog of active vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2 beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D-3 because of metabolism at the 2 beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2 beta-positon and a combination of metabolism between side chain and 2 beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2 beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2 beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method. (c) 2006 Elsevier Inc. All rights reserved.
• Synthesis and biological activities of the two C(23) epimers of 1α,23,25-trihydroxy-24-oxo-19-nor-vitamin D3: novel analogs of 1α,23(S),25-trihydroxy-24-oxo-vitamin D3, a natural metabolite of 1α,25-dihydroxyvitamin D3
  作者：Nancy E Lee、Paul G Williard、Alex J Brown、Moray J Campbell、H.Phillip Koeffler、Sara Peleg、D.Sunita Rao、G.Satyanarayana Reddy

  DOI：10.1016/s0039-128x(99)00110-5

  日期：2000.5

  In a previous report. we indicated that 1 alpha,23(S).25-trihydroxy-23-oxovitamin D-3 [1 alpha,23(S).25(OH)(3)-24-oxo-D-3], a natural metabolite of 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] is almost equipotent to 1 alpha,25(OH)(2)D-3 in suppressing parathyroid hormone (PTH) secretion (Lee et al., 1997. Biochemistry 36, 9429-9437). Also, 1 alpha,23(S),25(OH)(3)-24-oxo-D-3 has been shown to possess only weak in vivo calcemic actions. Thus. vitamin D-3 analogs structurally related to 1 alpha,23(S),25(OH)(3)-24-oxo-D-3 may have therapeutic value. Furthermore. biologic activity studies of various synthetic analogs of 1 alpha,25(OH)(2)D-3 showed that the removal of carbon-19 (C-19) reduces the calcemic activity of 1 alpha,25(OH)(2)D-3. Therefore, in an attempt to produce vitamin D-3 analogs with a better therapeutic index, we synthesized C(23) epimers of 1 alpha,23,25(OH)(3)-24-oxo-19-nor-vitamin D-3 1 alpha,23,25(OH)(3)-24-oxo-19-nor-D-3]. The two epimers were compared to 1 alpha,25(OH)(2)-19-nor-D-3 and 1 alpha.25(OH)(2)D-3 in their ability to generate biologic activities in several in vitro assay systems. In the assay measuring the suppression of parathyroid hormone (PTH) secretion in bovine parathyroid cells, 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 was as potent as 1 alpha,25(OH)(2)-19-nor-D-3 but was less potent than 1 alpha,25(OH)(2)D-3. In the same assay 1 alpha,23(R)25(OH)(3)-24-oxo-19-nor-D-3 exhibited greater potency than 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3. In the assays measuring the ability of vitamin D compounds to inhibit clonal growth and to induce differentiation of human promyelocytic leukemia (HL60) cells, 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 was less potent than 1 alpha,25(OH)(2)-19-nor-D-3 but was equipotent to 1 alpha,25(OH)(2)D-3. More importantly, in the same assays, 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 was more potent than 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 and was equipotent to 1 alpha,25(OH)(2)-19-nor-D-3. Also, the vitamin D receptor-mediated transcriptional activity or 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 was almost equal to that of 1 alpha,25(OH)(2)-19-nor-D-3, but higher than that of 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3. This finding explains in part the greater in vitro biologic activities of 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3. In summary, our results indicate that 1 alpha,23(R),25(OH)(3)-24-oxo-19-nor-D-3 and to a lesser extent 1 alpha,23(S),25(OH)(3)-24-oxo-19-nor-D-3 are potent 19-nor vitamin D-3 analogs, which suppress PTH secretion in bovine parathyroid cells and strongly inhibit clonal growth and induce differentiation of HL-60 cells in vitro. (C) 2000 Elsevier Science Inc. All rights reserved.
• Process for the preparation of ED-71
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1061070B1

  公开（公告）日：2008-07-16