5-amino-3-oxapentyl-β-D-galactopyranoside acetate | 213338-67-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-amino-3-oxapentyl-β-D-galactopyranoside acetate
• 英文别名: (2R,3R,4S,5R,6R)-2-(2-(2-aminoethoxy)ethoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol；(2R,3R,4S,5R,6R)-2-[2-(2-aminoethoxy)ethoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 213338-67-1
• 化学式: C₁₀H₂₁NO₇
• 分子量: 267.279
• InChiKey: UOWHZBJXUDKQCW-SOYHJAILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  135
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-amino-3-oxapentyl-β-D-galactopyranoside acetate 、 格尔德霉素 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以78%的产率得到17-demethoxy-17-{[2-(2-β-galactopyranosylethyl)ethyl]amino}geldanamycin
  参考文献：
  名称：

  Synthesis and Enzyme-Specific Activation of Carbohydrate−Geldanamycin Conjugates with Potent Anticancer Activity

  摘要：

  Geldanamycin (GA) is a potent anticancer antibiotic that inhibits Hsp90. Its potential clinical utility is hampered by its severe toxicity. To alleviate this problem, we synthesized a series of carbohydrate - geldanamycin conjugates for enzyine-specific activation to increase tumor selectivity. The conjugation was carried out at the C-17-position of GA. Their anticancer activity was tested in a number of cancer cell lines. The enzyme-specific activation of these conjugates M ion was evaluated with beta-galactosidase and beta-glucosidase. Evidently. glycosylation of C-17-pasition converted GA to an inactive prodrug before enzyme cleavage. Glucose-GA, as positive control, showed anticancer activity with IC50 of 70.2- 380.9 nM in various cancer cells by beta-glucocsidase activation inside of the tumor cells, which was confirmed by 3-fold inhibition using beta-glucasidase. specific inhibitor [2,5-dihydroxyniethy-3,4-dihydroxypyrrolidine (DMDP)]. Compared to glucose- GA, galactose- and lactose-GA conjugates exhibited much less activity with IC50 greater than 8000-25 000 nM. However, when galactose- and lactose-GA, were incubated with beta-galactosidase in the cells, their anticancer activity was enhanced by 3- to 40-fold. The results suggest, that GA can be inactivated by glycosylation of C-17-position and reactivated for anticancer activity by beta-galactosidase. Therefore, galactose-GA can be exploited in antibody-directed enzyme prodrug therapy (ADEPT) with beta-galactosidase for enzyme-specific activation in tumors. to increase tumor selectivity.

  DOI：

  10.1021/jm049693a
• 作为产物：
  描述：

  beta-D-半乳糖五乙酸酯 在 palladium on activated charcoal 4 A molecular sieve 、 氢气 、 sodium methylate 、 乙酸肼 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -30.0~60.0 ℃ 、344.74 kPa 条件下， 反应 22.0h， 生成 5-amino-3-oxapentyl-β-D-galactopyranoside acetate
  参考文献：
  名称：

  Synthesis and Enzyme-Specific Activation of Carbohydrate−Geldanamycin Conjugates with Potent Anticancer Activity

  摘要：

  Geldanamycin (GA) is a potent anticancer antibiotic that inhibits Hsp90. Its potential clinical utility is hampered by its severe toxicity. To alleviate this problem, we synthesized a series of carbohydrate - geldanamycin conjugates for enzyine-specific activation to increase tumor selectivity. The conjugation was carried out at the C-17-position of GA. Their anticancer activity was tested in a number of cancer cell lines. The enzyme-specific activation of these conjugates M ion was evaluated with beta-galactosidase and beta-glucosidase. Evidently. glycosylation of C-17-pasition converted GA to an inactive prodrug before enzyme cleavage. Glucose-GA, as positive control, showed anticancer activity with IC50 of 70.2- 380.9 nM in various cancer cells by beta-glucocsidase activation inside of the tumor cells, which was confirmed by 3-fold inhibition using beta-glucasidase. specific inhibitor [2,5-dihydroxyniethy-3,4-dihydroxypyrrolidine (DMDP)]. Compared to glucose- GA, galactose- and lactose-GA conjugates exhibited much less activity with IC50 greater than 8000-25 000 nM. However, when galactose- and lactose-GA, were incubated with beta-galactosidase in the cells, their anticancer activity was enhanced by 3- to 40-fold. The results suggest, that GA can be inactivated by glycosylation of C-17-position and reactivated for anticancer activity by beta-galactosidase. Therefore, galactose-GA can be exploited in antibody-directed enzyme prodrug therapy (ADEPT) with beta-galactosidase for enzyme-specific activation in tumors. to increase tumor selectivity.

  DOI：

  10.1021/jm049693a

文献信息

• Oligosaccharide-camptothecin conjugates as potential antineoplastic drugs: Design, synthesis and biological evaluation
  作者：Maolin Li、Wenchong Ye、Kaishuo Fu、Cui zhou、Yonghui Shi、Weiping Huang、Wenming Chen、Jiliang Hu、Zhilin Jiang、Wen Zhou

  DOI：10.1016/j.ejmech.2020.112509

  日期：2020.9

  Thirty novel 20 (S)-O-linked camptothecin (CPT) glycoconjugates were synthesized. They showed more potent in vitro cytotoxicities over irinotecan, but very weak direct topoisomerase I (Topo I) inhibition was observed at 100.0 μM. Oligosaccharide types, length of a PEG linker and acetyl groups exerted obvious effects on cytotoxicity, selectivity, water solubility and stability of the newly synthesized

  合成了三十种新颖的20（S）-O-连接的喜树碱（CPT）糖缀合物。他们表现出更有效的体外细胞毒性过伊立替康，但非常弱的直接拓扑异构酶I在100.0观察（TOPO I）抑制μ M.寡糖类型，PEG接头的长度和乙酰基作用于细胞毒性，选择性，水溶性明显影响，并新合成的CPT糖缀合物的稳定性。结构40与CPT相比，博来霉素（BLM）二糖与引入的酯部分中的二甘醇相连，具有更高的抗肿瘤活性和独特的选择性。静脉内动物急性毒性（160 mg / kg）未检测到毒性。总的来说，将具有靶向肿瘤的寡糖附着到CPT的20（S）-OH上可以为当前的Topo I毒药带来的艰巨问题提供解决方案。
• Galactose-decorated light-responsive hydrogelator precursors for selectively killing cancer cells
  作者：Wei Ji、Guofeng Liu、Fang Wang、Zhu Zhu、Chuanliang Feng

  DOI：10.1039/c6cc05707a

  日期：——

  Intracellular molecular self-assembly of gelators released from their precursors has shown promising applications in cancer therapy. However, the specifically targeting tumor cells and precise control of gelators release for the...

  从其前体释放的胶凝剂的细胞内分子自组装已在癌症治疗中显示出有希望的应用。然而，专门针对肿瘤细胞和精确控制胶凝剂释放的...
• A gulose moiety contributes to the belomycin (BLM) disaccharide selective targeting to lung cancer cells
  作者：Cui Zhou、Wenchong Ye、Yongjun Cao、Meizhu Wang、Dongxia Qi、Guohao Liao、Houkai Li、Weiping Huang、Wenming Chen、Xiaoyang Wang、Wen Zhou

  DOI：10.1016/j.ejmech.2021.113866

  日期：2021.12

  mono- or disaccharide analogues derived from BLM disaccharide, along with the corresponding carbohydate-dye conjugates have been designed and synthesized in this study, aiming at exploring the effect of a gulose residue on the cellular binding/uptake of BLM disaccharide and it possible uptake mechanism. Our evidence is presented indicating that, for the cellular binding/uptake of BLM disaccharide, a gulose

  本研究设计并合成了八种源自 BLM 二糖的单糖或二糖类似物以及相应的碳水化合物-染料偶联物，旨在探索古洛糖残基对 BLM 二糖细胞结合/摄取的影响及其可能的摄取机制。我们的证据表明，对于 BLM 二糖的细胞结合/摄取，古洛糖残基是必需的亚基，但与其化学性质无关。有趣的是，d -gulose-dye conjugate 能够选择性地靶向 A549 癌细胞，但l -gulose-dye conjugate 失败。进一步的摄取机制研究表明d与 BLM 二糖染料类似的-古洛糖染料衍生物以温度和 ATP 依赖性方式表现，并且部分受 GLUT1 受体指导。此外，与吉西他滨被其他单糖修饰的衍生物53b-c相比，修饰d-古洛糖的吉西他滨53a表现出更强的抗肿瘤活性。总之，单糖d-古洛糖缀合物提供了一种通过增加肺癌治疗中的肿瘤靶向来解决细胞毒性药物的新策略。
• Synthesis and Enzyme-Specific Activation of Carbohydrate−Geldanamycin Conjugates with Potent Anticancer Activity
  作者：Hao Cheng、Xianhua Cao、Ming Xian、Lanyan Fang、Tingwei Bill Cai、Jacqueline Jia Ji、Josefino B. Tunac、Duxin Sun、Peng George Wang

  DOI：10.1021/jm049693a

  日期：2005.1.1

  Geldanamycin (GA) is a potent anticancer antibiotic that inhibits Hsp90. Its potential clinical utility is hampered by its severe toxicity. To alleviate this problem, we synthesized a series of carbohydrate - geldanamycin conjugates for enzyine-specific activation to increase tumor selectivity. The conjugation was carried out at the C-17-position of GA. Their anticancer activity was tested in a number of cancer cell lines. The enzyme-specific activation of these conjugates M ion was evaluated with beta-galactosidase and beta-glucosidase. Evidently. glycosylation of C-17-pasition converted GA to an inactive prodrug before enzyme cleavage. Glucose-GA, as positive control, showed anticancer activity with IC50 of 70.2- 380.9 nM in various cancer cells by beta-glucocsidase activation inside of the tumor cells, which was confirmed by 3-fold inhibition using beta-glucasidase. specific inhibitor [2,5-dihydroxyniethy-3,4-dihydroxypyrrolidine (DMDP)]. Compared to glucose- GA, galactose- and lactose-GA conjugates exhibited much less activity with IC50 greater than 8000-25 000 nM. However, when galactose- and lactose-GA, were incubated with beta-galactosidase in the cells, their anticancer activity was enhanced by 3- to 40-fold. The results suggest, that GA can be inactivated by glycosylation of C-17-position and reactivated for anticancer activity by beta-galactosidase. Therefore, galactose-GA can be exploited in antibody-directed enzyme prodrug therapy (ADEPT) with beta-galactosidase for enzyme-specific activation in tumors. to increase tumor selectivity.