3{beta}-O-(3',3'-dimethylsuccinyl)lupeol

• 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: 3{beta}-O-(3',3'-dimethylsuccinyl)lupeol
• 英文别名: 3-O-(3',3'-dimethylsuccinyl)lupeol；4-[[(1R,3aR,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-1-isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxo-butanoic acid；4-[[(1R,3aR,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a,5a,5b,8,8,11a-hexamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid
• 化学式: C₃₆H₅₈O₄
• 分子量: 554.854
• InChiKey: UYFUPLFIKDRTIK-BNJJVXHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.8
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,3-dimethyl succinic anhydride 、 羽扇豆醇 在 吡啶 、 4-二甲氨基吡啶 作用下， 以70%的产率得到3{beta}-O-(3',3'-dimethylsuccinyl)lupeol
  参考文献：
  名称：

  Synthesis of new heterocyclic lupeol derivatives as nitric oxide and pro-inflammatory cytokine inhibitors

  摘要：

  A series of heterocyclic derivatives including indoles, pyrazines along with oximes and esters were synthesized from lupeol and evaluated for anti-inflammatory activity through inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 and J774A.1 cells. All the synthesized molecules of lupeol were found to be more active in inhibiting NO production with an IC50 of 18.4-48.7 mu M in both the cell lines when compared to the specific nitric oxide synthase (NOS) inhibitor, L-NAME (IC50 = 69.21 and 73.18 mu M on RAW 264.7 and J774A.1 cells, respectively). The halogen substitution at phenyl ring of indole moiety leads to potent inhibition of NO production with half maximal concentration ranging from 18.4 to 41.7 mu M. Furthermore, alkyl (11, 12) and p-bromo/iodo (15, 16) substituted compounds at a concentration of 20 mu g/mL exhibited mild inhibition (29-42%) of LPS-induced tumor necrosis factor alpha (TNF-alpha) and weak inhibition (10-22%) towards interleukin 1-beta (IL-1 beta) production in both the cell lines. All the derivatives were found to be non-cytotoxic when tested at their IC50 (mu M). These findings suggest that the derivatives of lupeol could be a lead to potent inhibitors of NO. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.032

文献信息

• Synthesis and in vitro antitumor activities of lupeol dicarboxylic acid monoester derivatives
  作者：Weijie Li、Jing Hao、Yeyu Xiao

  DOI：10.1007/s12272-013-0155-x

  日期：2013.12

  Ten lupeol dicarboxylic acid monoester derivatives as new potent antitumor agents were synthesized and evaluated for in vitro antitumor activities against A549, LAC, HepG2 and HeLa cell lines. Among them, compounds 1–5 showed excellent antitumor activities against all tested tumor cell lines and compounds 6–10 exhibited high activities against A549, HepG2 and HeLa cells, exceeded lupeol, lupanol and doxorubicin. Compound 2 displayed the highest potent antitumor activities with IC50 values of 5.78 μM against A549 cell, 2.38 μM against LAC cell, 6.14 μM against HepG2 cell and 0.00842 μM against HeLa cell.

  合成了 10 种作为新型有效抗肿瘤药物的羽扇豆醇二羧酸单酯衍生物，并评估了其对 A549、LAC、HepG2 和 HeLa 细胞系的体外抗肿瘤活性。其中，化合物1-5对所有测试的肿瘤细胞系均表现出优异的抗肿瘤活性，化合物6-10对A549、HepG2和HeLa细胞表现出较高的活性，超过了羽扇豆醇、羽扇豆醇和阿霉素。化合物 2 显示出最强的抗肿瘤活性，针对 A549 细胞的 IC50 值为 5.78 μM，针对 LAC 细胞的 IC50 值为 2.38 μM，针对 HepG2 细胞的 IC50 值为 6.14 μM，针对 HeLa 细胞的 IC50 值为 0.00842 μM。
• Anti-AIDS Agents 69. Moronic Acid and Other Triterpene Derivatives as Novel Potent Anti-HIV Agents
  作者：Donglei Yu、Yojiro Sakurai、Chin-Ho Chen、Fang-Rong Chang、Li Huang、Yoshiki Kashiwada、Kuo-Hsiung Lee

  DOI：10.1021/jm0601912

  日期：2006.9.1

  In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 mu M against NL4-3, 0.021 mu M against PI-R (a multiple protease inhibitor resistant strain), and 0.13 mu M against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.
• Synthesis of new heterocyclic lupeol derivatives as nitric oxide and pro-inflammatory cytokine inhibitors
  作者：Pamita Bhandari、Neeraj Kumar Patel、Kamlesh Kumar Bhutani

  DOI：10.1016/j.bmcl.2014.05.032

  日期：2014.8

  A series of heterocyclic derivatives including indoles, pyrazines along with oximes and esters were synthesized from lupeol and evaluated for anti-inflammatory activity through inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 and J774A.1 cells. All the synthesized molecules of lupeol were found to be more active in inhibiting NO production with an IC50 of 18.4-48.7 mu M in both the cell lines when compared to the specific nitric oxide synthase (NOS) inhibitor, L-NAME (IC50 = 69.21 and 73.18 mu M on RAW 264.7 and J774A.1 cells, respectively). The halogen substitution at phenyl ring of indole moiety leads to potent inhibition of NO production with half maximal concentration ranging from 18.4 to 41.7 mu M. Furthermore, alkyl (11, 12) and p-bromo/iodo (15, 16) substituted compounds at a concentration of 20 mu g/mL exhibited mild inhibition (29-42%) of LPS-induced tumor necrosis factor alpha (TNF-alpha) and weak inhibition (10-22%) towards interleukin 1-beta (IL-1 beta) production in both the cell lines. All the derivatives were found to be non-cytotoxic when tested at their IC50 (mu M). These findings suggest that the derivatives of lupeol could be a lead to potent inhibitors of NO. (C) 2014 Elsevier Ltd. All rights reserved.