5-(N-benzyloxycarbonyl)aminopentyl β-D-galactopyranoside | 160242-89-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 5-(N-benzyloxycarbonyl)aminopentyl β-D-galactopyranoside
• 英文别名: 5-(benzyloxycarbonylamino)pentyl β-D-galactopyranoside
• CAS: 160242-89-7
• 化学式: C₁₉H₂₉NO₈
• 分子量: 399.441
• InChiKey: ORTPOFYMORGCTF-DISONHOPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  28.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  137.71
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  5-(N-benzyloxycarbonyl)aminopentyl β-D-galactopyranoside 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 44.0h， 生成 17-demethoxy-17-[(2-β-galactopyranosylpentyl)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 4 A molecular sieve 、 sodium methylate 、 乙酸肼 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 5-(N-benzyloxycarbonyl)aminopentyl β-D-galactopyranoside
  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

• Mitochondrial Affinity of Guanidine-rich Molecular Transporters Built on Monosaccharide Scaffolds: Stereochemistry and Lipophilicity
  作者：Woo-Sirl Lee、Wan-Il Kim、Kyong-Tai Kim、Sung-Kee Chung

  DOI：10.5012/bkcs.2011.32.7.2286

  日期：2011.7.20

  We synthesized eight G8 molecular transporters (MTs) based on 4 different monosaccharide scaffolds, and studied their biological properties with a special focus on possible mitochondrial targeting and tissue selectivity. The mitochondrial affinity of these MTs was found to be clearly related to the scaffold stereochemistry and also tenuously with the lipophilicity. It may be suggested that in the practical delivery strategy of drugs for the brain and mitochondrial diseases the BBB permeability and mitochondrial affinity should be considered as key parameters, and that an enhanced mitochondrial affinity appears possible by further research on the structure-property relationship of guanidine-rich molecular transporters.

  我们合成了八种基于四种不同单糖支架的G8分子转运体（MTs），并研究了它们的生物特性，特别关注可能的线粒体靶向性和组织选择性。这些MT的线粒体亲和力明显与支架的立体化学相关，也与疏水性有一定联系。可以建议，在针对大脑和线粒体疾病的药物实际递送策略中，应将血脑屏障渗透性和线粒体亲和力视为关键参数，并且通过进一步研究富含胍的分子转运体的结构—性质关系，增强线粒体亲和力是可行的。
• Synthesis of the 5-aminopentyl glycoside of β-d-Galp-(1 → 4)-β-d-GlcpNAc-(1 → 3)-l-Fucp and fragments thereof related to glycopeptides of human Christmas factor and the marine sponge Microciona prolifera
  作者：Thomas Ziegler

  DOI：10.1016/0008-6215(94)84179-9

  日期：1994.9

  The marine sponge Microciona prolifera and human coagulation factor IX (Christmas factor)-related mono- to tri-saccharide 5-aminopentyl glycosides beta-D-Gal p-R (5), beta-D-Glc pNAc-R (16), beta-D-Gal p-(1-->4)-beta-D-Glc p NAc-R (26), beta-D-Glc p NAc-(1-->3)-beta-L-Fuc p-R (39), beta-D-Glc pNAc-(1-->3)-alpha-L-Fuc p-R (43), beta-D-Gal p-(1-->4)-beta-D- Glc pNAc-(1-->3)-beta-L-Fuc p-R (45), and beta-D-Gal

  海洋海绵Microciona增殖和人类凝血因子IX（圣诞节因子）相关的单糖至三糖5-氨基戊基糖苷β-D-GalpR（5），β-D-GlcpNAc-R（16），β- D-Gal p-（1-> 4）-beta-D-Glc p NAc-R（26），beta-D-Glc p NAc-（1-> 3）-beta-L-Fuc pR（39 ），β-​​D-GlcpNAc-（1-> 3）-α-L-FucpR（43），β-D-Galp-（1-> 4）-β-D-GlcpNAc-（ 1-> 3）-beta-L-Fuc pR（45）和beta-D-Gal p-（1-> 4）-beta-D-Glc p NAc-（1-> 3）-alpha制备了-L-Fuc pR（47），其中R是5-氨基戊氧基间隔基，其允许糖缀合物的构建。因此，3,4,6-三-O-乙酰基-2-脱氧-2-（2,2,2-三氯乙氧基羰基-氨基）-α-D-吡喃葡萄糖基三氯乙酰亚氨酸盐（10）和1
• Design, synthesis and biological evaluation of the positional isomers of the galactose conjugates able to target hepatocellular carcinoma cells via ASGPR-mediated cellular uptake and cytotoxicity
  作者：Wenchong Ye、Qun Tang、Tiantian Zhou、Cui Zhou、Chuangchuang Fan、Xiaoyang Wang、Chunmei Wang、Keyu Zhang、Guochao Liao、Wen Zhou

  DOI：10.1016/j.ejmech.2023.115988

  日期：2024.1