1-(tert-butyldimethylsilyl)-7-deacetylforskolin | 105535-46-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 1-(tert-butyldimethylsilyl)-7-deacetylforskolin
• 英文别名: (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-10-[tert-butyl(dimethyl)silyl]oxy-3-ethenyl-5,6,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-1-one
• CAS: 105535-46-4
• 化学式: C₂₆H₄₆O₆Si
• 分子量: 482.733
• InChiKey: KMCURCAREGEVQC-UIXRHWCESA-N

物化性质

• 熔点：
  60-62 °C
• 沸点：
  531.4±50.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(tert-butyldimethylsilyl)-7-deacetylforskolin 在 4-二甲氨基吡啶 、 sodium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 [2-(Trityl-amino)-acetylamino]-acetic acid (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-10-(tert-butyl-dimethyl-silanyloxy)-5,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-3-vinyl-dodecahydro-benzo[f]chromen-6-yl ester
  参考文献：
  名称：

  Lal, Bansi; Gangopadhyay, Ashok Kumar; Gidwani, Ramesh M., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 1, p. 232 - 246

  摘要：

  DOI：
• 作为产物：
  描述：

  佛司可林 在 咪唑 、 potassium carbonate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.0h， 生成 1-(tert-butyldimethylsilyl)-7-deacetylforskolin
  参考文献：
  名称：

  Cardiovascular effects of new water-soluble derivatives of forskolin

  摘要：

  A series of 6- and 7-aminoacyl derivatives of 7-deacetylforskolin was prepared to provide water-soluble derivatives of the potent cardioactive diterpenoid forskolin. The compounds were evaluated for positive inotropic and blood pressure lowering properties in pharmacological models. Several derivatives displayed potent positive inotropic activity in guinea pig atria (EC50 = 0.16-3.0 micrograms/mL). In the most active compounds, the amino moiety of the aminoacyl chain corresponded to a cyclic amine, and the acyl moiety to a C2-C4 alkanoyl group. In vivo biological evaluation led to the selection of 6-(piperidinoacetyl)-7-deacetylforskolin hydrochloride (49) as a candidate for clinical development.

  DOI：

  10.1021/jm00118a002

文献信息

• Labdane compounds, pharmaceutical compositions and use
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US04639443A1

  公开（公告）日：1987-01-27

  Novel labdanes, intermediates and processes for the preparation thereof, and methods for reducing intraocular pressure utilizing compounds or compositions thereof are disclosed.

  本发明揭示了用于制备新型拉丹烷化合物、中间体和制备方法，以及利用这些化合物或组合物减少眼内压力的方法。
• Forskolin Derivatives. I. Synthesis, and Cardiovascular and Adenylate Cyclase-Stimulating Activities of Water-Soluble Forskolins.
  作者：Tochiro TATEE、Aya NARITA、Kazuhisa NARITA、Giichi IZUMI、Takashi TAKAHIRA、Masao SAKURAI、Akira FUJITA、Makoto HOSONO、Kouwa YAMASHITA、Keiko ENOMOTO、Akira SHIOZAWA

  DOI：10.1248/cpb.44.2274

  日期：——

  Water-soluble forskolin and 7-deacetylforskolin derivatives with an aminoacetyl, a 3-aminopropionyl, or a 4-aminobutyryl group at the 6- or 7-position were prepared, and their positive inotropic as well as vasodilative activities were evaluated in anesthetized dogs.7-Deacetylforskolin (2) and 7-deacetyl-1-silylforskolin (6) were converted to the corresponding 7-chloroacylderivatives (3, 7, 10), which were reacted with amines to obtain 7-aminoacyl-7-deacetylforskolins (4a-f, 9a, b, 11). The 7-acyl substituents migrated to the 6-position with sodium hydroxide in acetonitrile-water to afford 6-aminoacyl-7-deacetylforskolins (12a-f). The 7-position of 12a, d-f was selectively acetylated with acetyl chloride to obtain the corresponding 6-aminoacylforskolins (13a-d).Among the 6-aminoacylforskolins, 6-(3-dimethylaminopropionyl)forskolin (13b) and 6-(4-dimethylaminobutyryl)forskolin (13d) exhibited potent positive inotropic and vasodilative activities comparable to those of forskolin (1).The activities of 13b and 13d were approximately ten times more potent than those of 7-aminoacyl- and 6-aminoacyl-7-deacetylforskolins (4a-f, 9a, 12a-c, f). 6-Dimethylaminoacetylforskolin (13a) and 6-(3-diethylaminopropionyl)forskolin (13c) were less potent than 1. The effects of the soluble forskolins on adenylate cyclase activity were also examined in vitro. 6-Aminoacylforskolins (13a-d) exhibited potent adenylate cyclase-stimulating activity, comparable to that of 1.

  制备了在 6-或 7-位具有氨基乙酰基、3-氨基丙酰基或 4-氨基丁酰基的水溶性毛喉素和 7-去乙酰基毛喉素衍生物，并在麻醉狗中评估了它们的正性肌力和血管舒张活性。将7-脱乙酰基毛喉素(2)和7-脱乙酰基-1-甲硅烷基毛喉素(6)转化为相应的7-氯酰基衍生物(3,7,10),与胺反应得到7-氨酰基-7-脱乙酰基毛喉素(4a- f、9a、b、11)。在乙腈-水中，用氢氧化钠将 7-酰基取代基迁移到 6-位，得到 6-氨基酰基-7-脱乙酰基毛喉素 (12a-f)。用乙酰氯选择性乙酰化12a、d-f的7位，得到相应的6-氨基酰基毛喉素(13a-d)。6-氨基酰基毛喉素中，6-(3-二甲基氨基丙酰基)毛喉素(13b)和6-(4-毛喉素)二甲氨基丁酰)forskolin (13d) 表现出与 forskolin (1) 相当的强正性肌力和血管舒张活性。13b 和 13d 的活性比 7-氨酰基-和 6-氨酰基-7-脱乙酰基 forskolin 的活性大约强十倍（ 4a-f、9a、12a-c、f)。 6-二甲氨基乙酰基毛喉素 (13a) 和 6-(3-二乙氨基丙酰基)毛喉素 (13c) 的效力低于 1。可溶性毛喉素对腺苷酸环化酶活性的影响也在体外进行了检测。 6-氨基酰基毛喉素 (13a-d) 表现出有效的腺苷酸环化酶刺激活性，与 1 相当。
• ——
  作者：

  DOI：——

  日期：——
• Hydroxyacyl derivatives of forskolin—their positive inotropic activity
  作者：Bansi Lal、Ashok Kumar Gangopadhyay、Ramanujam Rajagopalan、Anil Vasantrao Ghate

  DOI：10.1016/s0968-0896(98)00123-0

  日期：1998.11

  Using appropriate protection and deprotection sequence novel hydroxyacyl chains of the type CO(CH2)(n)OH are synthesized and are utilized to develop new analogues of forskolin. Several compounds showed good positive inotropic activity. Compound 12 is almost 10 times more active than forskolin (EC50 = 0.002 mu g/ml).]. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Lal, Bansi; Gangopadhyay, Ashok Kumar; Rajagopalan, Ramanujam, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 11, p. 2308 - 2313
  作者：Lal, Bansi、Gangopadhyay, Ashok Kumar、Rajagopalan, Ramanujam、Ghate, Anil V.

  DOI：——

  日期：——