(8β,20S)-8-[(tert-butyldimethylsilyl)oxy]des-A,B-pregnan-20-ol | 147725-62-0

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (8β,20S)-8-[(tert-butyldimethylsilyl)oxy]des-A,B-pregnan-20-ol
• 英文别名: (20S)-des-A,B-8β-[(tert-butyldimethylsilyl)oxy]pregnan-20-ol；(20S)-De-A,B-8β-[(tert-butyldimethylsilyl)oxy]pregnan-20-ol；(1S)-1-((1S,3aR,4S,7aR)-4-{[tert-butyl(dimethyl)silyl]oxy}-7a-methyloctahydro-1H-inden-1-yl)ethanol；(S)-1-[(1S,3aR,4S,7aR)-4-(tert-Butyldimethyl-silanyloxy)7a-methyl-octahydro-inden-1-yl]ethanol；(1S)-1-[(1S,3aR,4S,7aR)-4-[tert-butyl(dimethyl)silyl]oxy-7a-methyl-1,2,3,3a,4,5,6,7-octahydroinden-1-yl]ethanol
• CAS: 147725-62-0
• 化学式: C₁₈H₃₆O₂Si
• 分子量: 312.568
• InChiKey: QDFQHDWFYMRCJG-ULQWZQFMSA-N

物化性质

• 沸点：
  351.8±15.0 °C(Predicted)
• 密度：
  0.94±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.97
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (8β,20S)-8-[(tert-butyldimethylsilyl)oxy]des-A,B-pregnan-20-ol 在 吡啶 、 三氯氧磷 作用下， 反应 22.0h， 以94%的产率得到(E)-des-A,B-8β-[(tert-butyldimethylsilyl)oxy]pregn-17(20)-ene
  参考文献：
  名称：

  具有不同大小侧链的16-烯-22-噻-1α，25-二羟基-26,27-二甲基-19-降钙素D3类似物的合成及其构效关系。

  摘要：

  我们已经合成了八个带有不同大小侧链的16-ene-22-thia-26,27-二甲基-19-norvitamin D3类似物1-5，与20S和20R异构体结合在一起。通过A-环氧化膦与具有不同侧链尺寸的16-烯-22-噻-25-羟基格伦德曼酮的Wittig-Horner反应制备目标化合物，所述酮衍生自作为主要中间体的S-苯氧羰基衍生物13。研究了合成的22-thia-19-norvitamin D类似物1-5对维生素D受体（VDR）的结合亲和力，VDR介导的转录活性和破骨细胞诱导活性。就体外测试的生物学活性而言，（20S）-22-硫杂-19,24-地诺维生素D类似物1a与天然激素1α，25-二羟基维生素D3（1α，25-（OH）2D3）具有相同的活性。类似物2a和3a在与VDR的结合中表现出与1alpha，25-（OH）2D3几乎相同的效能，在转录活性方面比1alpha，25-（OH）2D

  DOI：

  10.1016/j.bmc.2007.11.013
• 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 咪唑 、 potassium tert-butylate 、 氧气 、 氢化钾 、 碳酸氢钠 、 二甲基亚砜 作用下， 以 异丙醇 、 叔丁醇 为溶剂， 生成 (8β,20S)-8-[(tert-butyldimethylsilyl)oxy]des-A,B-pregnan-20-ol
  参考文献：
  名称：

  A new approach to the synthesis of the 25-hydroxy-22-oxa-vitamin D3 side chain

  摘要：

  An efficient new method is described for the construction of the 25-hydroxy-22-oxavitamin D-3 side-chain, which is present in several analogues of calcitriol with antitumour activity. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)01056-3

文献信息

• VITAMIN D RECEPTOR ACTIVATORS AND METHODS OF MAKING
  申请人：Von Geldern Thomas W.

  公开号：US20090131379A1

  公开（公告）日：2009-05-21

  The invention relates to compounds that are vitamin D receptor activators, compositions comprising such compounds, methods of using such compounds and compositions, processes for preparing such compounds, and intermediates obtained during such processes.

  该发明涉及一种维生素D受体激活剂化合物，包括这种化合物的组合物，使用这种化合物和组合物的方法，制备这种化合物的过程，以及在这些过程中获得的中间体。
• Synthesis of Novel Hapten Derivatives of 1α,25-Dihydroxy-vitamin D₃ and Its 20-Epi Analogue¹
  作者：Lars K. A. Blæhr,*、Fredrik Björkling、Martin J. Calverley、Ernst Binderup、Mikael Begtrup

  DOI：10.1021/jo026061s

  日期：2003.2.1

  Hapten derivatives of 1alpha,25-dihydroxyvitamin D(3) and its 20-epimer were synthesized and conjugated to a carrier protein for raising polyclonal antibodies. The haptens were linked through spacers at C-16, thereby exposing both the A-ring and the side chain of the molecules, to maximize antibody specificity. The spacers were introduced via stereoselective hydroboration of 16-ene intermediates as

  合成了1alpha，25-dihydroxyvitamin D（3）的Hapten衍生物及其20个受体，并将其缀合到载体蛋白上以产生多克隆抗体。半抗原通过在C-16处的间隔基连接，从而暴露分子的A环和侧链，以最大化抗体特异性。间隔基是通过16烯中间体的立体选择性硼氢化引入的，这是关键步骤。在免疫测定中，针对天然激素的抗体相对于具有A环或侧链修饰的衍生物对该化合物具有选择性。然而，针对20个末端的抗体不能识别侧链中的修饰。
• Dermatological use of vitamin D derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US05827883A1

  公开（公告）日：1998-10-27

  A method of using vitamin D derivatives of the formula ##STR1## wherein X is .dbd.CH.sub.2 or H,H; Y is a moiety --CH(CH.sub.3)--(A).sub.n --C(O)--OR.sup.1 (a) --CH(CH.sub.3)--CH.sub.2 --O--C(O)--R.sup.2 (b) or --C(O)--OR.sup.1 (c); A is --CH.dbd.CH-- or CH.sub.2 --CH.sub.2 -- R.sup.1 is lower alkyl, cycloalkyl, cycloalkylmethyl, --CH.sub.2 R.sup.3 or --CH.sub.2 --CH.sub.2 R.sup.3 ; R.sup.2 is lower alkyl, cycloalkyl or R.sup.3 ; R.sup.3 is hydroxy-lower alkyl, hydroxy-cycloalkyl or trifluoromethyl-hydroxy-lower-alkyl; n is 0 or 1; and the dotted bond in the five membered ring is optional; in the treatment of dermatological conditions, in particular keratinization disorders such as psoriasis, as well as acne and photodamaged skin, is described. Vitamin D derivatives of the formula I above, wherein X, Y, A, R.sup.1, R.sup.2, R.sup.3 and n are as set forth above; with the proviso that X is H,H when Y is --CH(CH.sub.3)--CH.sub.2 --OC(O)--C(OH)(CH.sub.3).sub.2 and the dotted bond in the five-membered ring is not present; as well as a process for the preparation of the compounds of formula I, and pharmaceutical compositions containing a compound of the formula I wherein X, Y, A, R.sup.1, R.sup.2, R.sup.3 and n are set forth above; with the proviso that X is H,H when Y is --CH(CH.sub.3)--CH.sub.2 --OC(O)--C(OH)(CH.sub.3).sub.2 and the dotted bond in the five-membered ring is not present, are also described.

  使用公式I中的维生素D衍生物的方法，其中X是.dbd.CH.sub.2或H,H; Y是一个基团--CH(CH.sub.3)--(A).sub.n--C(O)--OR.sup.1 (a) --CH(CH.sub.3)--CH.sub.2--O--C(O)--R.sup.2 (b)或--C(O)--OR.sup.1 (c); A是--CH.dbd.CH--或CH.sub.2--CH.sub.2--; R.sup.1是较低的烷基，环烷基，环烷基甲基，--CH.sub.2R.sup.3或--CH.sub.2--CH.sub.2R.sup.3; R.sup.2是较低的烷基，环烷基或R.sup.3; R.sup.3是羟基较低烷基，羟基环烷基或三氟甲基羟基较低烷基; n为0或1; 五元环中的虚线键是可选的; 描述了在治疗皮肤病症方面，特别是角化异常症如银屑病，以及痤疮和光损伤皮肤中使用。还描述了公式I中的维生素D衍生物，其中X，Y，A，R.sup.1，R.sup.2，R.sup.3和n如上所述; 假设当Y为--CH(CH.sub.3)--CH.sub.2--OC(O)--C(OH)(CH.sub.3).sub.2时，X为H，H，并且五元环中的虚线键不存在; 以及制备公式I化合物的过程，以及含有公式I中化合物的制药组合物，其中X，Y，A，R.sup.1，R.sup.2，R.sup.3和n如上所述; 假设当Y为--CH(CH.sub.3)--CH.sub.2--OC(O)--C(OH)(CH.sub.3).sub.2时，X为H，H，并且五元环中的虚线键不存在。
• From Hydrindane to Decalin: A Mild Transformation through a Dyotropic Ring Expansion
  作者：Hugo Santalla、Olalla Nieto Faza、Generosa Gómez、Yagamare Fall、Carlos Silva López

  DOI：10.1021/acs.orglett.7b01621

  日期：2017.7.7

  An unexpected ring expansion converting hydrindane cores into decalins has been observed. The process occurs under very mild conditions and with exquisite transfer of chiral information. The ring expansion provides access to decorated decalins with complete stereocontrol. The reaction mechanism is studied in order to gain insight into the underlying causes for the low thermal requirements in this reaction

  已经观察到意外的环膨胀，其将氢化茚满核转化为十氢化萘。该过程在非常温和的条件下进行，并且手性信息传递精细。扩环功能使您可以通过完全的立体声控制来访问装饰过的十氢化萘。对反应机理进行了研究，以便深入了解此反应中低热量要求的根本原因以及手性转移过程的性质。有趣的是，这两者都是由涉及甲磺酸盐基团的前所未有的促渗反应引起的。
• Synthesis and biological activities of new 1α,25-dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain
  作者：Masato Shimizu、Yukiko Miyamoto、Emi Kobayashi、Mika Shimazaki、Keiko Yamamoto、Wolfgang Reischl、Sachiko Yamada

  DOI：10.1016/j.bmc.2006.01.061

  日期：2006.6

  In a series of studies on structure-activity relationships of 2-substituted 19-norvitamin D analogs, we found that 1 alpha,25-dihydroxy-19-norvitamin D-3 analogs with 2 beta-hydroxyethoxy or 2E-hydroxyethylidene moieties show strong binding affinity for the vitamin D receptor (VDR) as well as marked transcriptional activity. To further examine the effects of side chain structure on the activity of 2-substituted 19-norvitamin D analogs, we have synthesized new 19-norvitamin D3 analogs with modifications in both the A-ring at the C(2) position and the side chain. The side chains of these analogs contained a double bond between C(22) and C(23) or an oxygen atom at C(22). The biological activity of the analogs was evaluated in vitro. All the side chain-modified analogs were less active than 1 alpha,25-dihydroxyvitamin D-3 1e and the parent compounds 3-6e possessing a natural 20R-configuration in binding to the VDR, but, except for the (20R)-22-oxa analogs 3-6d, were significantly more potent in transcriptional activity. Of the side-chain-modified analogs 4 and 5, the 2 beta-hydroxyethoxy- and 2E-hydroxyethylidene-22,24-diene-24a,26a,27a-trihorno analogs showed markedly higher transcriptional activity (25- and 17.5-fold, respectively) compared with le. Elongation of the side chain at the C-24, C-26, and C-27 positions and introduction of a 22,24-diene moiety strongly increased transcriptional activity, as seen in the 20-epi analogs 3-6f. (c) 2006 Elsevier Ltd. All rights reserved.