3β,12β-dihydroxy-23,24,25,26,27-hexanordammarane-20-one

• 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: 3β,12β-dihydroxy-23,24,25,26,27-hexanordammarane-20-one
• 英文别名: 3β,12β-diol-22,23,24,25,26,27-hexanordammaran-20-one；3,12-dihydroxy-4,4,8,10,14-pentamethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-ylethan-1-one；20-oxoprotopanaxadiol；1-[(3S,5R,8R,9R,10R,12R,13R,14R,17S)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
• 化学式: C₂₄H₄₀O₃
• 分子量: 376.58
• InChiKey: HCAQWVKVUOLAIG-FKHSOBLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3β,12β-dihydroxy-23,24,25,26,27-hexanordammarane-20-one 在 disodium hydrogenphosphate 、 间氯过氧苯甲酸 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 72.0h， 以52%的产率得到7-hydroxy-1,1,5a,10a,10b-pentamethyl-3-oxohexadecahydro-1H-cyclopenta[5,6]naphtho[2,1-c]oxepin-8-yl acetate
  参考文献：
  名称：

  Synthesis of selective 11 β -HSD1 inhibitors based on dammarane scaffold

  摘要：

  Inspired by natural 11 beta-HSD1 inhibitors hupehenols A - E, a ring-focused strategy was applied for the synthesis of 35 structurally diverse dammarane-type derivatives. These derivatives were effectively prepared from protopanaxadiol based on the modification of rings A and D. Among these compounds, ten were identified as selective 11 beta-HSD1 inhibitors (IC50 range: 101-1047 nM, SI range: 8-169) which exhibited inhibitory activities against human or mouse 11 beta-HSD1. Otherwise, we found 23a could selectively inhibit both human and mouse 11 beta-HSD1 with IC50 value of 994 and 213 nM (SI > 10 and > 47), respectively. Additionally, the molecular modelling results of 23a docking into the human and mouse 11 beta-HSD1 were in good agreement with the results from the enzyme inhibitory experiment. Moreover, valuable structural-activity relationship (SAR) information of dammarane-type 11 beta-HSD1 inhibitor was summarized. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.059
• 作为产物：
  描述：

  原人参二醇 在 吡啶 、 4-二甲氨基吡啶 、 sodium periodate 、 四氧化锇 、 palladium 10% on activated carbon 、 氢气 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 30.0h， 生成 3β,12β-dihydroxy-23,24,25,26,27-hexanordammarane-20-one
  参考文献：
  名称：

  (20S,24R)-epoxy-dammarane-3β,12β,25-三醇衍生物作为α-葡萄糖苷酶和PTP1B抑制剂的合成和生物学评价

  摘要：

  我们之前的研究中从青钱柳中获得的达玛烷三萜(20 S ,24 R )-epoxy-dammarane-3 β ,12 β ,25- triol 在体外对α-葡萄糖苷酶有抑制活性，抑制率为32.2%。浓度为 200 μM。为了揭示构效关系（SARs）并获得更多活性化合物，对羟基进行化学修饰合成了(20 S ,24 R )-epoxy-dammarane-3 β ,12 β ,25-triol 的42个衍生物。 （C-3 和 C-12），环 A 和 E，并测定它们的α-葡萄糖苷酶和PTP1B抑制活性。两种化合物 ( 8 , 26 ) 增加了对α-葡萄糖苷酶的活性，四种化合物 ( 8 , 15 , 26 , 42 ) 显着抑制了 PTP1B。值得注意的是，化合物8和26作为双靶点抑制剂可同时抑制α-葡萄糖苷酶和 PTP1B，其 IC 50值为 489.8、467.7 μM（α-葡萄糖苷酶）和 319

  DOI：

  10.1007/s00044-021-02836-0

文献信息

• 达玛烷三萜衍生物及其药物组合物和其在制药 中的应用
  申请人：中国科学院昆明植物研究所

  公开号：CN103709223B

  公开（公告）日：2016-08-31

  式（I）所示的达玛烷型三萜衍生物及其药用盐，其制备方法，以其为有效成分的药物组合物，它们在制备治疗或预防肥胖、糖尿病、高血压及心脑血管疾病及其相关的代谢性疾病药物中的应用，它们在制备11β‑HSD1抑制剂中的应用。
• Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3β,12β,25-triol derivatives as α-glucosidase and PTP1B inhibitors
  作者：Xiao-Tong Yang、Tian-Ze Li、Chang-An Geng、Pei Liu、Ji-Jun Chen

  DOI：10.1007/s00044-021-02836-0

  日期：2022.2

  activity against α-glucosidase, and four compounds (8, 15, 26, 42) significantly inhibited PTP1B. It was noted that compounds 8 and 26 could inhibit both α-glucosidase and PTP1B as dual-target inhibitors with IC50 values of 489.8, 467.7 μM (α-glucosidase) and 319.7, 269.1 μM (PTP1B). Compound 26 was revealed to be a mix-type inhibitor on α-glucosidase and a noncompetitive-type inhibitor on PTP1B based

  我们之前的研究中从青钱柳中获得的达玛烷三萜(20 S ,24 R )-epoxy-dammarane-3 β ,12 β ,25- triol 在体外对α-葡萄糖苷酶有抑制活性，抑制率为32.2%。浓度为 200 μM。为了揭示构效关系（SARs）并获得更多活性化合物，对羟基进行化学修饰合成了(20 S ,24 R )-epoxy-dammarane-3 β ,12 β ,25-triol 的42个衍生物。 （C-3 和 C-12），环 A 和 E，并测定它们的α-葡萄糖苷酶和PTP1B抑制活性。两种化合物 ( 8 , 26 ) 增加了对α-葡萄糖苷酶的活性，四种化合物 ( 8 , 15 , 26 , 42 ) 显着抑制了 PTP1B。值得注意的是，化合物8和26作为双靶点抑制剂可同时抑制α-葡萄糖苷酶和 PTP1B，其 IC 50值为 489.8、467.7 μM（α-葡萄糖苷酶）和 319
• Synthesis of selective 11 β -HSD1 inhibitors based on dammarane scaffold
  作者：Li-Dong Shao、Ying Bao、Yu Shen、Jia Su、Ying Leng、Qin-Shi Zhao

  DOI：10.1016/j.ejmech.2017.04.059

  日期：2017.7

  Inspired by natural 11 beta-HSD1 inhibitors hupehenols A - E, a ring-focused strategy was applied for the synthesis of 35 structurally diverse dammarane-type derivatives. These derivatives were effectively prepared from protopanaxadiol based on the modification of rings A and D. Among these compounds, ten were identified as selective 11 beta-HSD1 inhibitors (IC50 range: 101-1047 nM, SI range: 8-169) which exhibited inhibitory activities against human or mouse 11 beta-HSD1. Otherwise, we found 23a could selectively inhibit both human and mouse 11 beta-HSD1 with IC50 value of 994 and 213 nM (SI > 10 and > 47), respectively. Additionally, the molecular modelling results of 23a docking into the human and mouse 11 beta-HSD1 were in good agreement with the results from the enzyme inhibitory experiment. Moreover, valuable structural-activity relationship (SAR) information of dammarane-type 11 beta-HSD1 inhibitor was summarized. (C) 2017 Elsevier Masson SAS. All rights reserved.