3β-[(4-carboxyl)butyryloxy]-lup-20(29)-en-28-oic acid

• 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: 3β-[(4-carboxyl)butyryloxy]-lup-20(29)-en-28-oic acid
• 英文别名: A18；3-O-glutaryl-betulinic acid；(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-(5-hydroxy-5-oxo-pentanoyl)oxy-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylic acid；(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-(4-carboxybutanoyloxy)-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylic acid
• 化学式: C₃₅H₅₄O₆
• 分子量: 570.81
• InChiKey: ZTROUPGCRHSXAO-RTKWQOCYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  氯甲酸乙酯 、 3β-[(4-carboxyl)butyryloxy]-lup-20(29)-en-28-oic acid 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  New hybrids between triterpenoid acids and nucleoside HIV-RT inhibitors

  摘要：

  One-pot synthesis of ester-linked conjugates of betulinic, ursolic or oleanolic acids with anti-HIV drugs AZT, derivatives of AZT and 3TC was performed, the resulting conjugates having shown high anti-HIV activities.

  DOI：

  10.1016/j.mencom.2015.03.004
• 作为产物：
  描述：

  戊二酸酐 、 白桦脂酸 在 吡啶 、 4-二甲氨基吡啶 作用下， 以82%的产率得到3β-[(4-carboxyl)butyryloxy]-lup-20(29)-en-28-oic acid
  参考文献：
  名称：

  五环三萜3β-酯衍生物作为新型胆固醇酯转移蛋白抑制剂的发现

  摘要：

  设计，合成和评估了一系列五环三萜3β-酯衍生物，将其作为治疗血脂异常的一类新的胆固醇酯转移蛋白（CETP）抑制剂。体外筛选试验表明，30种化合物中有5种显示出适度的抑制人CETP活性，IC 50小于10μM。其中，化合物20（IC 50  = 2.3μM）具有最强的生物学活性，可有效改善人脂肪组织特异性CETP转基因（ap2-CETPTg）小鼠和豚鼠的血浆脂质水平。额外的安全性评估（豚鼠没有血压升高）和药代动力学研究表明，化合物20的潜在可药性 这是开发用于治疗血脂异常的新型CETP抑制剂的有希望的先导。

  DOI：

  10.1016/j.ejmech.2017.08.012

文献信息

• Inhibitory Effects of Constituents from Cynomorium songaricum and Related Triterpene Derivatives on HIV-1 Protease.
  作者：Chaomei MA、Norio NAKAMURA、Hirotsugu MIYASHIRO、Masao HATTORI、Kunitada SHIMOTOHNO

  DOI：10.1248/cpb.47.141

  日期：——

  From CH2Cl2 and MeOH extracts of the stems of Cynomorium songaricum RUPR. (Cynomoriaceae), ursolic acid and its hydrogen malonate were isolated as inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, with 50% inhibitory concentrations (IC50) of 8 and 6 μM, respectively. Amongst various synthesized dicarboxylic acid hemiesters of related triterpenes, inhibitory activity tended to increase in the order of oxalyl, malonyl, succinyl and glutaryl hemiesters, for triterpenes such as ursolic acid, oleanolic acid and betulinic acid. The most potent inhibition was observed for the glutaryl hemiesters, with an IC50 of 4 μM.From the water extract of the stems of C. songaricum, flavan-3-ol polymers, consisting of epicatechin as their extender flavan units, were also found to be potent inhibitory principles against HIV-1 protease.

  从锁阳（Cynomorium songaricum RUPR.）茎的CH2Cl2和MeOH提取物中，分离得到了熊果酸及其丙二酸氢化物，它们是人类免疫缺陷病毒1型（HIV-1）蛋白酶的抑制剂，其半数抑制浓度（IC50）分别为8和6微摩尔。在合成的各种相关三萜二羧酸半酯中，对于熊果酸、齐墩果酸和白桦脂酸等三萜类化合物，抑制活性倾向于按草酰、丙二酰、琥珀酰和戊二酰半酯的顺序增加。其中，戊二酰半酯显示出最强的抑制作用，IC50为4微摩尔。从锁阳茎的水提取物中，还发现了由表儿茶素构成扩展单元的黄烷-3-醇聚合物，它们也是HIV-1蛋白酶的强效抑制剂。
• Anticancer Activity of 3-<i>O</i>-Acylated Betulinic Acid Derivatives Obtained by Enzymatic Synthesis
  作者：Faujan Bin H. AHMAD、Mansour GHAFFARI MOGHADDAM、Mahiran BASRI、Mohd Basyaruddin ABDUL RAHMAN

  DOI：10.1271/bbb.90917

  日期：2010.5.23

  An easy and efficient strategy to prepare betulinic acid esters with various anhydrides was used by the enzymatic synthesis method. It involves lipase-catalyzed acylation of betulinic acid with anhydrides as acylating agents in organic solvent. Lipase from Candida antarctica immobilized on an acrylic resin (Novozym 435) was employed as a biocatalyst. Several 3-O-acyl-betulinic acid derivatives were successfully obtained by this procedure. The anticancer activity of betulinic acid and its 3-O-acylated derivatives were then evaluated in vitro against human lung carcinoma (A549) and human ovarian (CAOV3) cancer cell lines. 3-O-glutaryl-betulinic acid, 3-O-acetyl-betulinic acid, and 3-O-succinyl-betulinic acid showed IC50<10 μg/ml against A549 cancer cell line tested and showed better cytotoxicity than betulinic acid. In an ovarian cancer cell line, all betulinic acid derivatives prepared showed weaker cytotoxicity than betulinic acid.

  一种简便高效的策略通过酶合成方法制备了白桦酸的各种酐酯。该方法涉及在有机溶剂中使用酐作为酰化剂，通过脂肪酶催化白桦酸的酰化反应。采用了固定在丙烯酸树脂上的南极假丝酵母脂肪酶（Novozym 435）作为生物催化剂。通过这一步骤成功获得了几种3-O-酰基白桦酸衍生物。随后，评估了白桦酸及其3-O-酰化衍生物对人肺腺癌（A549）和人卵巢癌（CAOV3）细胞系的体外抗癌活性。3-O-戊二酰白桦酸、3-O-乙酰白桦酸和3-O-琥珀酰白桦酸对A549癌细胞系的IC50值小于10微克/毫升，并且显示出比白桦酸更强的细胞毒性。在卵巢癌细胞系中，所有制备的白桦酸衍生物的细胞毒性均弱于白桦酸。
• Anti-AIDS agents—XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives
  作者：Fumio Hashimoto、Yoshiki Kashiwada、L.Mark Cosentino、Chin-Ho Chen、Patricia E. Garrett、Kuo-Hsiung Lee

  DOI：10.1016/s0968-0896(97)00158-2

  日期：1997.12

  lupane-type triterpenoic acid derivatives were synthesized and evaluated for their inhibitory activity against HIV-1 replication in acutely infected H9 cells, based on the fact that betulinic acid (1) and dihydrobetulinic acid (9) were identified as anti-HIV agents. Among the derivatives, 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (3) and 3-O-(3',3'-dimethylsuccinyl)-dihydrobetulinic acid (11) both demonstrated

  基于以下事实，合成了两个系列的卢烷型三萜酸衍生物，并评估了其在抗急性感染的H9细胞中对HIV-1复制的抑制活性，这是基于将桦木酸（1）和二氢白菜酸（9）鉴定为抗HIV的事实。代理商。在这些衍生物中，3-O-（3'，3'-二甲基琥珀酰基）-丁二酸（3）和3-O-（3'，3'-二甲基琥珀酰基）-二氢丁二酸（11）均显示出极强的抑制活性EC50值<3.5 x 10（-4）microM，并且显着的体外治疗指数（TI）值分别为20,000和14,000。3-O-（3'，3'-二甲基戊二芳基）-贝丁酸（4）和-二氢贝丁酸（12）3-O-二甘醇-丁二酸（5）和-二氢贝丁酸（13）和3-O-戊二酰-丁二酸（6）也是有效的HIV复制抑制剂，EC50值为0.04至2.3 x 10（-3） ）的microM和TI值在292至2344之间。此外，化合物11和12在单核细胞系和外周血单核细胞中也具有抗HIV复制的活
• Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors
  作者：Dongyin Chen、Xin Huang、Hongwen Zhou、Hanqiong Luo、Pengfei Wang、Yongzhi Chang、Xinyi He、Suiying Ni、Qingqing Shen、Guoshen Cao、Hongbin Sun、Xiaoan Wen、Jun Liu

  DOI：10.1016/j.ejmech.2017.08.012

  日期：2017.10

  A series of pentacyclic triterpene 3β-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC50s less than 10 μM. Among them, compound 20 (IC50 = 2.3 μM) had the most potent biological

  设计，合成和评估了一系列五环三萜3β-酯衍生物，将其作为治疗血脂异常的一类新的胆固醇酯转移蛋白（CETP）抑制剂。体外筛选试验表明，30种化合物中有5种显示出适度的抑制人CETP活性，IC 50小于10μM。其中，化合物20（IC 50  = 2.3μM）具有最强的生物学活性，可有效改善人脂肪组织特异性CETP转基因（ap2-CETPTg）小鼠和豚鼠的血浆脂质水平。额外的安全性评估（豚鼠没有血压升高）和药代动力学研究表明，化合物20的潜在可药性 这是开发用于治疗血脂异常的新型CETP抑制剂的有希望的先导。
• New hybrids between triterpenoid acids and nucleoside HIV-RT inhibitors
  作者：Anh Thi Tuyet Dang、Chinh The Pham、Tuan Anh Le、Hieu Hong Truong、Ha Thu Thi Vu、Anatoly T. Soldatenkov、Tuyen Van Nguyen

  DOI：10.1016/j.mencom.2015.03.004

  日期：2015.3

  One-pot synthesis of ester-linked conjugates of betulinic, ursolic or oleanolic acids with anti-HIV drugs AZT, derivatives of AZT and 3TC was performed, the resulting conjugates having shown high anti-HIV activities.