11beta,18-环氧-18,21-二羟基孕甾-4-烯-3,20-二酮 | 6251-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 中文名称: 11beta,18-环氧-18,21-二羟基孕甾-4-烯-3,20-二酮
• 英文名称: aldosterone
• 英文别名: Aldosteron；Aldosterone hemiacetal；(1R,2S,5S,6S,14R,15S,16S)-18-hydroxy-2-(2-hydroxyacetyl)-14-methyl-17-oxapentacyclo[14.2.1.01,5.06,15.09,14]nonadec-9-en-11-one
• CAS: 6251-69-0
• 化学式: C₂₁H₂₈O₅
• 分子量: 360.45
• InChiKey: QUQBHBRVKLEOEI-UBWIUKTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  11beta,18-环氧-18,21-二羟基孕甾-4-烯-3,20-二酮 在 吡啶 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 50.17h， 生成
  参考文献：
  名称：

  醛固酮葡糖醛酸，重要的生物标志物：新型异构体的合成和结构解析

  摘要：

  醛固酮1是盐皮质激素，它对血压有很大的影响，其葡糖醛酸苷是检测多种疾病的重要标志。在这里，我们描述了不同醛固酮18和20葡糖醛酸内酯的化学合成。在TMSOTf存在下，三甲基甲硅烷基2,3,4-三乙酰基-1-β-葡萄糖醛酸甲酯5b与醛固酮二乙酸酯11的反应得到18-α-葡萄糖醛酸9a。18-β葡萄糖醛酸苷15b中与20-β葡萄糖醛酸苷16b中可以通过甲基的反应而获得2,3,4-三ö异丁酰基1α葡糖醛三氯14和醛固酮21-乙酸酯8在将TMSOTf或BF的存在3 ⋅OEt 2。最后，在TMSOTf存在下，醛固酮21-乙酸8与2,3,4-三乙酰基-1α-葡萄糖醛酸三氯乙酰胺酸甲酯19反应，得到相应的18-β-三乙酰基葡萄糖醛酸甲酯9 b，然后将其转化为所需的醛固酮18 -β-葡萄糖醛酸3通过两个酶促转化。

  DOI：

  10.1002/chem.202004154
• 作为产物：
  描述：

  (11beta)-11,18-环氧-21-羟基孕甾-4-烯-3,20-二酮 在 Krebs-Ringer-bicarbonate-glucose buffer 、 male CHBB-Thom rat adrenal mitochondria 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 11beta,18-环氧-18,21-二羟基孕甾-4-烯-3,20-二酮
  参考文献：
  名称：

  Inhibition of aldosterone formation by cortisol in rat adrenal mitochondria

  摘要：

  In this work we confirm by a metabolic method the existence of at least two enzymes with 11 beta- and 18-hydroxylase activities in rat adrenal mitochondria. The method was based on the ability of cortisol (F), a foreign alternative substrate, to inhibit competitively metabolite productions from various precursors. F inhibited a) aldosterone (ALDO) production from 11-deoxycorticosterone (DOG) without affecting the yields of corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18-OHDOC); b) 18-hydroxycorticosterone and aldosterone productions from B (K-i = 2.5 +/- 0.5 mu M); and c) ALDO production from 18-OHDOC. These results suggest the existence of two categories of enzymes with both 11 beta- and 18-hydroxylase activities, one comprising those that catalyze the conversions of DOC to B and 18-OHDOC (F-insensitive reactions [FIS]) and the other one comprising the enzymes involved in the conversions of B to 18-OHB and ALDO and that of 18-OHDOC to ALDO (F-sensitive reactions [FS]). The cloned enzymes CYP11B1 and CYP11B2 would pertain respectively to the FIS and FS categories.

  DOI：

  10.1016/0039-128x(94)00064-j

文献信息

• Preparation and Structural Elucidation of the Picolinyl Ester of Aldosterone for Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry
  作者：Kouwa Yamashita、Yumiko Tadokoro、Madoka Takahashi、Mitsuteru Numazawa

  DOI：10.1248/cpb.56.873

  日期：——

  Treatment of aldosterone with 35% HCl in EtOH or in MeOH followed by the picolinyl derivatization gave the picolinyl derivative of aldosterone-ethyl ether, 8, or methyl ether, 9, as a single and well-shaped liquid chromatographic peak. Picolinyl derivatization of aldosterone produced 21-picolinyl derivative of 18,20-anhydro-hemiacetal derivatives, 6, with poor chromatographic peak with wide half-width. Further conversion of 6 to 8 required long reaction time (>4 h). Structure of each picolinyl or alkyl ether-picolinyl derivative, was carefully elucidated by nuclear magnetic resonance spectroscopy, electron ionization mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Enhancement of sensitivity (approximately 10-fold) in positive-LC-ESI-MS/MS of aldosterone was confirmed by the use of the alkyl ether-picolinyl derivatization when compared to the underivatized molecule.

  用 35% HCl 在 EtOH 或 MeOH 中处理醛固酮，然后进行吡啶基衍生化，可得到醛固酮-乙醚的吡啶基衍生物 8 或甲醚的吡啶基衍生物 9，其液相色谱峰单一且形状良好。醛固酮的吡啶基衍生化产生了 18,20-anhydro-hemiacetal 衍生物的 21-吡啶基衍生物 6，其色谱峰较差，半宽较宽。将 6 进一步转化为 8 需要较长的反应时间（>4 小时）。通过核磁共振光谱法、电子电离质谱法和液相色谱-电喷雾串联质谱法（LC-ESI-MS/MS），仔细阐明了每种皮啶或烷基醚-皮啶衍生物的结构。与未充分活化的分子相比，通过使用烷基醚-匹考林基衍生化，醛固酮的正液相色谱-电喷雾离子化-质谱/质谱灵敏度得到了提高（约 10 倍）。
• 18-substituted steroids. part 18. chemical synthesis and mineralocorticoid activity of 2α- and 2β-hydroxyaldosterone
  作者：David N. Kirk、Martin H. Schröder、Syed A. Latif、Graham W. Souness、David J. Morris

  DOI：10.1016/0039-128x(93)90053-p

  日期：1993.2

  The 2 alpha-hydroxy and 2 beta-hydroxy derivatives of aldosterone have been synthesized chemically from aldosterone, after the earlier identification of 2 alpha-hydroxylated metabolites formed in liver. Both 2 alpha- and 2 beta-hydroxyaldosterone are potent mineralocorticoids, with activities on the order of 1/10 that of aldosterone on the basis of a rat bioassay.

  在较早鉴定出肝脏中形成的2个α-羟基化代谢物后，醛固酮的化学合成醛固酮的2个α-羟基和2个β-羟基衍生物。2α-和2β-羟基醛固酮都是有效的盐皮质激素，根据大鼠生物测定法，其活性约为醛固酮的1/10。
• 18-Substituted steroid. Part 15. 6β-hydroxylation of aldosterone by liver
  作者：David N. Kirk、Philip J. Burke、Harold C. Toms、Syed A. Latif、David J. Morris

  DOI：10.1016/0039-128x(89)90092-5

  日期：1989.8

  6 beta-Hydroxyaldosterone and 6 beta-hydroxy-17-isoaldosterone, characterized by high-field NMR studies, are among the major polar metabolites formed from aldosterone by incubation with rat liver slices or microsomal fraction. It is uncertain at present whether the 17-iso product results from an enzymatic or a chemical inversion of configuration. Periodate degradation of the 6 beta-hydroxyaldosterone

  以高场NMR研究为特征的6β-羟基醛固酮和6β-羟基-17-异醛固酮是由醛固酮与大鼠肝脏切片或微粒体温育形成的主要极性代谢产物。目前尚不确定17-iso产物是由构型的酶促转化还是化学转化而产生。6β-羟基醛固酮的高碘酸盐降解产生6β-羟基醛固酮γ-内酯，与合成样品相同。
• Differences between adrenal adenoma causing primary aldosteronism and other adrenal tissues in the incorporation of labeled steroid precursors into their products
  作者：Toshitaka Usa、Arunabha Ganguly、Myron H. Weinberger

  DOI：10.1016/0039-128x(80)90076-8

  日期：1980.11

  The incorporation and conversion of several labeled steroid precursors into their products were examined in slices of adrenal tissue from two patients with primary aldosteronism and compared with that in "normal" adrenal tissue and adrenal tissues from a patient with Cushing's syndrome. The products of the incorporation were separated by Sephadex LH-20 column chromatography. The major products of conversion in the adenomatous tissue of primary aldosteronism were 18-hydroxycorticosterone and lesser amounts of aldosterone. Smaller amounts of 18-hydroxycorticosterone were isolated from all other adrenal tissues studied. No aldosterone could be recovered after incubating any of the adrenal tissue studied with labeled 18-hydroxy-11-deoxycorticosterone or 18-hydroxycorticosterone as precursor steroid. These in vitro results seem to suggest that there is increased 18-hydroxylation in the adenoma of primary aldosteronism compared with other tissues and that relatively more 18-hydroxycorticosterone is produced in such tissue than aldosterone.
• Kirk, David N.; Miller, Barry W.; Cooley, George, Journal of Chemical Research, Miniprint, 1989, # 6, p. 1274 - 1289
  作者：Kirk, David N.、Miller, Barry W.、Cooley, George、Latif, Syed A.、Morris, David J.

  DOI：——

  日期：——