6β-methyl-estra-1,3,5(10)-triene-3,17β-diol | 88899-74-5

• 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: 6β-methyl-estra-1,3,5(10)-triene-3,17β-diol
• 英文别名: 6β-Methyl-oestra-1,3,5(10)-trien-3,17β-diol；(6R,8R,9S,13S,14S,17S)-6,13-dimethyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
• CAS: 88899-74-5
• 化学式: C₁₉H₂₆O₂
• 分子量: 286.414
• InChiKey: GIWQIXCJHHWPIT-WWELPLAASA-N

物化性质

• 熔点：
  222-225 °C
• 沸点：
  444.5±45.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  6β-methylestrone 在 sodium tetrahydroborate 作用下， 生成 6β-methyl-estra-1,3,5(10)-triene-3,17β-diol
  参考文献：
  名称：

  Steroids. CXIII.¹ 6-Methyl Estrogens

  摘要：

  DOI：

  10.1021/jo01085a006

文献信息

• Synthesis and GC-MS of 6-Alkylestradiols, Possible Aromatase Reaction Products of 6-Alkylandrostenediones.
  作者：Mitsuteru NUMAZAWA、Akiko YOSHIMURA

  DOI：10.1248/cpb.44.1530

  日期：——

  A series of 6α- and 6β-alkylestradiols (5 and 6) (alkyl : methyl, ethyl, n-propyl, n-pentyl, and n-heptyl) were synthesized as possible aromatase reaction products of 6-alkylandrost-4-ene-3, 17-diones and their Δ1-derivatives, potent competitive and mechanism-based inhibitors of aromatase. Treatment of 6-oxoestradiol with Grignard reagents followed by acid-catalyzed dehydration and subsequent catalytic hydrogenation over Pd-C gave the 6-alkylestradiols (5 and 6). GC-MS (electron impact mode) of trimethylsilyl derivatives of bis-trimethylsilyl derivatives of compounds 5 and 6 revealed that the 6α-alkyl compounds, 5, emerged with a longer retention time compared to the corresponding 6β-alkyl isomers, 6, where the retention time was in proportion to the length of the 6-alkyl chain in each series. In the MS, a molecular ion (M+) peak was the base peak for all the 6-alkylestrogens, with strong and characteristic fragment ion peaks corresponding to M+-131 and at m/z 325. A selected ion monitoring method using a molecular ion will be sensitive enough for analysis of the aromatization reaction of the 6-alkylandrogens.

  合成了一系列6α-和6β-烷基雌二醇（5和6）（烷基：甲基、乙基、正丙基、正戊基和正庚基），作为6-烷基雄烯-3, 17-二酮及其Δ1衍生物的可能芳香化反应产物，这些化合物是强竞争性和机制基础的芳香化酶抑制剂。将6-氧雌二醇与格林纳反应试剂处理，经过酸催化脱水和随后在Pd-C上的催化加氢，得到了6-烷基雌二醇（5和6）。通过气相色谱-质谱（电子轰击模式）分析化合物5和6的双三甲基氯硅烷衍生物，发现6α-烷基化合物5的保留时间比相应的6β-烷基异构体6长，且每个系列中保留时间与6-烷基链的长度成正比。在质谱中，所有6-烷基雌激素的母离子（M+）峰是基峰，且具有强烈且特征性的碎片离子峰，分别对应于M+-131和m/z 325。使用母离子进行选择性离子监测的方法将对6-烷基雄烯的芳香化反应分析足够敏感。
• Synthesis and Biochemical Studies of 19-Oxygenated Derivatives of 6.ALPHA.- and 6.BETA.-Methylandrostenediones as Catalytic Probes for the Active Site of Aromatase.
  作者：Mitsuteru NUMAZAWA、Akiko YOSHIMURA

  DOI：10.1248/bpb.23.1059

  日期：——

  To gain insight into the binding aspects of 6α- and 6β-methylandrostenediones (1 and 2), potent competitive inhibitors and effective substrates of aromatase, at the active site of the enzyme, we synthesized their 19-hydroxy and 19-oxo derivatives to determine their inhibition of aromatase activity as well as their aromatization rates in human placental microsomes. The 6β- and 6α-methyl-19-ols 12 and 13 were produced from 19-(tert-butyl-dimethylsiloxy)androstenedione (6) in 6 steps in which the Grignard reaction of 5α, 6α-epoxy steroid 8 with CH3MgBr was employed as a key reaction. Oxidation of the 19-ols 12 and 13 yielded the corresponding 19-als 14 and 15. The 6α-methyl steroids 13 and 15 were good competitive inhibitors of aromatase (Ki≤100 nM), and their aromatization rates obtained by gas chromatography-mass spectrometric analysis were 110 and 205pmol/min/mg protein, respectively. In contrast, the 6β-methyl isomers 12 and 14 were non-competitive inhibitors, with Ki values of more than 500 nM, and they were aromatized at rates of 16 and 20 pmol/min/mg protein, respectively. These results reveal that there is a marked difference in binding to the active site between the 19-oxygenated 6α-methyl and 6β-methyl inhibitors where the binding manner of the 6α-steroids, rather than the 6β-isomers, is suitable as a substrate for aromatase.

  6α- 和 6β- 甲基雄烯二酮（1 和 2）是芳香化酶的强效竞争性抑制剂和有效底物，为了深入了解它们与芳香化酶活性位点的结合情况，我们合成了它们的 19- 羟基和 19- 氧代衍生物，以确定它们对芳香化酶活性的抑制作用以及它们在人类胎盘微粒体中的芳香化率。6β-和 6α-甲基-19-醇 12 和 13 是由 19-（叔丁基-二甲基硅氧基）雄烯二酮（6）经 6 个步骤合成的，其中 5α、6α-环氧类固醇 8 与 CH3MgBr 的格氏反应被用作关键反应。19- 醇 12 和 13 氧化生成相应的 19-醛 14 和 15。6α- 甲基类固醇 13 和 15 是芳香化酶的良好竞争性抑制剂（Ki≤100 nM），通过气相色谱-质谱分析获得的芳香化率分别为 110 和 205pmol/min/mg。相反，6β-甲基异构体 12 和 14 是非竞争性抑制剂，Ki 值超过 500 nM，它们的芳香化率分别为 16 和 20 pmol/min/mg。这些结果表明，19-氧代 6α- 甲基和 6β- 甲基抑制剂与活性位点的结合存在明显差异，其中 6α- 类固醇而非 6β- 异构体的结合方式适合作为芳香化酶的底物。