(3R,5S,8R,9S,10S,13S,14S)-3-(methoxymethoxy)-10,13-dimethylHexadecahydro- 17H-cyclopenta[a]phenanthren-17-one | 1135993-39-3

• 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: (3R,5S,8R,9S,10S,13S,14S)-3-(methoxymethoxy)-10,13-dimethylHexadecahydro- 17H-cyclopenta[a]phenanthren-17-one
• 英文别名: (3R,5S,8R,9S,10S,13S,14S)-3-(methoxymethoxy)-10,13-dimethylHexadecahydro-17H-cyclopenta[a]phenanthren-17-one；3α-methoxymethoxy-5α-androstan-17-one；3α-Methoxymethoxyandrostan-17-on
• CAS: 1135993-39-3
• 化学式: C₂₁H₃₄O₃
• 分子量: 334.499
• InChiKey: ORCGXARMXKAWSV-XVYLQWLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.59
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (3R,5S,8R,9S,10S,13S,14S)-3-(methoxymethoxy)-10,13-dimethylHexadecahydro- 17H-cyclopenta[a]phenanthren-17-one 在 sodium tetrahydroborate 、 sodium hydride 、 乙酰氯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 mineral oil 为溶剂， 反应 7.0h， 生成 3α-hydroxy-17β-methoxy-5α-androstane
  参考文献：
  名称：

  Direct measurements of neurosteroid binding to specific sites on GABAA receptors

  摘要：

  Background and PurposeNeurosteroids are allosteric modulators of GABAA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady‐state binding affinities of various neurosteroids for specific sites on the GABAA receptor.Experimental ApproachTwo methods were developed to measure neurosteroid binding affinity: (1) quenching of specific tryptophan residues in neurosteroid binding sites by the neurosteroid 17‐methylketone group, and (2) FRET between MQ290 (an intrinsically fluorescent neurosteroid) and tryptophan residues in the binding sites. The assays were developed using ELIC‐α1GABAAR, a chimeric receptor containing transmembrane domains of the α1‐GABAA receptor. Tryptophan mutagenesis was used to identify specific interactions.Key ResultsAllopregnanolone (3α‐OH neurosteroid) was shown to bind at intersubunit and intrasubunit sites with equal affinity, whereas epi‐allopregnanolone (3β‐OH neurosteroid) binds at the intrasubunit site. MQ290 formed a strong FRET pair with W246, acting as a site‐specific probe for the intersubunit site. The affinity and site‐specificity of several neurosteroid agonists and inverse agonists was measured using the MQ290 binding assay. The FRET assay distinguishes between competitive and allosteric inhibition of MQ290 binding and demonstrated an allosteric interaction between the two neurosteroid binding sites.Conclusions and ImplicationsThe affinity and specificity of neurosteroid binding to two sites in the ELIC‐α1GABAAR were directly measured and an allosteric interaction between the sites was revealed. Adaptation of the MQ290 FRET assay to a plate‐reader format will enable screening for high affinity agonists and antagonists for neurosteroid binding sites.

  DOI：

  10.1111/bph.16490
• 作为产物：
  描述：

  雄酮 、 氯甲基甲基醚 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.3h， 以77%的产率得到(3R,5S,8R,9S,10S,13S,14S)-3-(methoxymethoxy)-10,13-dimethylHexadecahydro- 17H-cyclopenta[a]phenanthren-17-one
  参考文献：
  名称：

  γ-和δ-氰基-N-甲苯磺酰腙与烯基硼酸的立体选择性多米诺碳环化反应，在四元立体中心上形成两个不同的C(sp3)-C(sp2)键

  摘要：

  通过烯基硼酸与δ-或γ-氰基-N-甲苯磺酰腙的级联碳环化，定义了一种合成功能化碳环的新策略。在该反应中，两个 C(sp(3))-C(sp(2)) 键形成在前一个腙碳上，产生全碳季立体中心，并导致环状酮具有完全非对映选择性的烯基侧链。这些过程是在非常简单的实验条件下进行的，仅在 K2CO3 存在下，以 1,4-二恶烷为溶剂并在微波辐射下进行，并已应用于合成各种结构的稠合环戊酮和环己酮。此外，这种方法的多功能性已在雄酮的结构修饰中得到证明。

  DOI：

  10.1021/jacs.6b08116

文献信息

• Pd(PPh3)4/AgOAc-catalyzed coupling of 17-steroidal triflates and alkynes: Highly efficient synthesis of D-ring unsaturated 17-alkynylsteroids
  作者：Qian Sun、Chenggang Jiang、Hangxian Xu、Zonglei Zhang、Lanhai Liu、Cunde Wang

  DOI：10.1016/j.steroids.2010.05.018

  日期：2010.12

  and various 1-alkynes by Pd(PPh(3))(4)/AgOAc-catalyzed in the presence of DIPEA for 24h to yield the desired D-ring unsaturated 17-alkynyl steroids (86-97%). Moreover, it was found that the coupling reaction catalyzed by Pd[(C(6)H(5))(3)P](4)/AgOAc system is selective for aryl triflates or vinyl triflates. By optimizing the reaction conditions, the sole C17-coupling products from steroidal bistriflates

  开发了一种新颖实用的方法，用于通过 Pd(PPh(3))(4)/AgOAc 催化偶联的甾体 17-三氟甲磺酸酯和炔烃制备 D 环不饱和 17-炔基类固醇。首先用 PhN(Tf)(2) 和 KHMDS 在干燥的 THF 中在 -78 摄氏度下处理类固醇 17-酮 2 小时，在偶联后以高产率 (97-98%) 得到相应的类固醇 17-三氟甲磺酸酯产物在 DIPEA 存在下，通过 Pd(PPh(3))(4)/AgOAc 催化 17-三氟甲磺酸酯和各种 1-炔烃反应 24 小时，得到所需的 D 环不饱和 17-炔基类固醇 (86-97%) . 此外，发现由 Pd[(C(6)H(5))(3)P](4)/AgOAc 系统催化的偶联反应对芳基三氟甲磺酸酯或乙烯基三氟甲磺酸酯具有选择性。通过优化反应条件，以令人满意的收率获得了来自甾体双三氟甲磺酸酯的唯一 C17 偶联产物。由于具有共轭双键和三重键的 D 环不饱和
• [EN] NMDAR INHIBITING AGENTS AND GABAAR POTENTIATING AGENTS AND USES THEREOF<br/>[FR] AGENTS INHIBITEURS DE NMDAR ET AGENTS DE POTENTIALISATION GABAAR ET LEURS UTILISATIONS
  申请人：COVEY DOUGLAS

  公开号：WO2021080880A1

  公开（公告）日：2021-04-29

  N-methyl-d-aspartate receptors (NMDAR) and/or potentiating y-aminobutyric acid receptors (GABAAR) agents and uses thereof are described. Uses of these agents include methods of treating or preventing various psychiatric diseases, disorders, or conditions and methods of treating or preventing alcohol use disorder in a subject in need thereof.

  描述了N-甲基-d-天冬氨酸受体（NMDAR）和/或增强γ-氨基丁酸受体（GABAAR）药物及其用途。这些药物的用途包括治疗或预防各种精神疾病、障碍或病况的方法，以及治疗或预防需要的受试者中的酒精使用障碍的方法。
• Generation of Fused Seven-Membered Polycyclic Systems via Ring Expansion and Application to the Total Synthesis of Sesquiterpenoids
  作者：Zhimin Xing、Bowen Fang、Shangwen Luo、Xingang Xie、Xiaolei Wang

  DOI：10.1021/acs.orglett.2c01401

  日期：2022.6.10

  methods for synthesizing fused medium-sized bicyclo[m.n.0] ring systems, including the benzo-cycloheptane systems, are still urgent. Herein we describe a base-induced ring expansion as a general strategy to construct a wide range of fused seven-membered ring systems. The application of this method was demonstrated by the efficient total syntheses of two sesquiterpenoids, plecarpenene and plecarpenone

  广泛存在于天然产物和分子药物中的七元多环结构是具有挑战性的合成靶标。然而，合成融合中型双环的方法[ m . n .0] 环系统，包括苯并环庚烷系统，仍然是紧迫的。在这里，我们将碱基诱导的环扩展描述为构建广泛的稠合七元环系统的一般策略。该方法的应用通过两种倍半萜类化合物 plecarpenene 和 plecarpenone 的高效全合成得到证明，两者均具有稠合的双环 [5.3.0] 癸烷骨架。
• 10.3184/030823408x333409
  作者：Bian, Xiaoqin、Li, Shuangshuang、Gang, Xin、Liu, Lanhai、Xie, Zengyang、Wang, Cunde

  DOI：10.3184/030823408x333409

  日期：——