2-deoxy-2-phthalimido-β-D-glucopyranose | 31505-45-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-deoxy-2-phthalimido-β-D-glucopyranose
• 英文别名: N,N-phthaloyl-β-D-glucosamine；N-phthaloyl glucosamine；2-[(2R,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]isoindole-1,3-dione
• CAS: 31505-45-0
• 化学式: C₁₄H₁₅NO₇
• 分子量: 309.276
• InChiKey: LWHWPIHFMAOQQQ-GOBQNSBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-deoxy-2-phthalimido-β-D-glucopyranose 在 吡啶 、 ammonium cerium (IV) nitrate 、 2,4-二甲基吡啶 、 三氟甲磺酸三甲基硅酯 、 三氟化硼乙醚 、 sodium methylate 、 对甲苯磺酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 硫脲 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.84h， 生成 p-methoxyphenyl 4,6-di-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1→4)-2,3-di-O-benzoyl-6-O-levulinoyl-β-D-glucopyranoside
  参考文献：
  名称：

  Synthesis and Immunological Characterization of Modified Hyaluronic Acid Hexasaccharide Conjugates

  摘要：

  The synthesis of a tetanus toxoid (TT)-conjugate of a hyaluronic acid (HA) hexasaccharide is described. The compound was intended for use in monitoring HA levels as a disease marker and as a potential vaccine against Group A Streptococcus (GAS) infections. We also report the synthesis of a chemically modified HA-hexasaccharide-TT conjugate in which the N-acetyl moiety of the N-acetyl-D-glucosamine residue is replaced with an N-propionyl unit in order to enhance immunogenicity. The oligosaccharides are synthesized in a convergent manner. The TT-conjugate syntheses rely on the reaction of the amines on the 6-aminohexyl aglycon of the hexasaccharides with diethyl squarate to give the monoethyl squarate adducts. Subsequent reactions with lysine epsilon-amino groups on TT then give the glycoconjugates containing an average of 8 hexasaccharide haptens per TT molecule. Immunological studies in mice show very similar antibody responses with both conjugates, suggesting that the N-acetyl groups of the glucosaminyl residues of the HA-hexasaccharide are not a critical part of the epitope recognized by the anti-HA polyclonal immune response. Furthermore, it would appear that the N-acyl moieties are not in close contact with the amino acid residues of the antibody combining sites.

  DOI：

  10.1021/jo4012442
• 作为产物：
  描述：

  D-glucosamine hydrochloride 在 sodium methylate 、 三乙胺 作用下， 反应 0.17h， 生成 2-deoxy-2-phthalimido-β-D-glucopyranose
  参考文献：
  名称：

  Grover, Parul; Singh, Jitender; Dhar, Journal of the Indian Chemical Society, 2009, vol. 86, # 10, p. 1112 - 1114

  摘要：

  DOI：

文献信息

• Synthesis and characterization of N-acyl-tetra-O-acyl glucosamine derivatives
  作者：Chi-Hien Dang、Cong-Hao Nguyen、Thanh-Danh Nguyen、Chan Im

  DOI：10.1039/c3ra46007j

  日期：——

  Novel 1,3,4,6-tetra-O-acyl-N-acyl-D-glucosamine derivatives were synthesized from glucosamine hydrochloride (GlcN·HCl) by the acylation with pyridine as a catalyst. A derivative of tetra-O-acetyl glucosamine contained ketoprofen, a non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects, was first synthesized. In analysis of the NMR spectra, the ratio of α:β-anomer showed that penta-acyl-D-glucosamine derivatives and N-acetylated glucosamines containing O-acyl groups have been only the α-anomer. Meanwhile, both the intermediates and the glucoconjugate compound of ketoprofen have only the β-anomer.

  利用吡啶作为催化剂，通过酰化反应从葡萄糖胺盐酸盐（GlcN·HCl）合成了新型1,3,4,6-四-O-酰基-N-酰基-D-葡萄糖胺衍生物。首次合成了一种含有酮洛芬的四-O-乙酰基葡萄糖胺衍生物，酮洛芬是一种具有镇痛和退热作用的无菌性抗炎药物（NSAID）。通过NMR谱图分析，α:β-异构体的比例表明，含有O-酰基的五酰基-D-葡萄糖胺衍生物和N-乙酰化的葡萄糖胺均为α-异构体。同时，酮洛芬的中间体和葡萄糖结合物均为β-异构体。
• Synthesis of analogues of calicheamicin and neocarzinostatin chromophore
  作者：Alessandra Cirla、Angela R McHale、John Mann

  DOI：10.1016/j.tet.2004.03.021

  日期：2004.4

  The work presents a synthetic route to the CD ring of calicheamicin and in the case of neocarzinostatin an approach to a functionalised cyclopentane-1,3-diol containing the naturally occurring naphthoate and a glucosamine motif. In the case of the NCS derivative some biological activity (cytotoxicity) was observed.

  这项工作为加利车霉素的CD环提供了一条合成途径，在新carcarinostatin的情况下，提出了一种含有天然萘酚和葡糖胺基序的功能化环戊烷1,3-二醇的方法。在NCS衍生物的情况下，观察到一些生物学活性（细胞毒性）。
• Design, synthesis and evaluation of cytotoxic properties of bisamino glucosylated antitumor ether lipids against cancer cells and cancer stem cells
  作者：Makanjuola Ogunsina、Pranati Samadder、Temilolu Idowu、Gilbert Arthur、Frank Schweizer

  DOI：10.1039/c6md00328a

  日期：——

  diamino-D-gluco-based GAELs and their analogs, and screened them against a panel of human epithelial cancer cell lines and cancer stem cells. Most of the new GAEL analogs are more potent than chlorambucil, cisplatin and salinomycin. The most potent bisamine-based GAEL analogs 1, 2, 4 and 8 showed 2- to 3-fold enhanced cytotoxicity against various cancer cell lines when compared to β-GLN, indicating that the addition

  糖基化抗肿瘤醚脂质（GAEL）是一类通过非凋亡途径杀死癌细胞的两亲性抗肿瘤药。以前的研究已经表明，2-氨基-2-脱氧d -葡萄糖为基础的盖尔如α-GLN和β-GLN显示出大大改善的抗上皮癌细胞的抗肿瘤活性和干细胞。为了进一步优化生物活性，我们制备了一系列二氨基的d -葡糖基础的盖尔和它们的类似物，并筛选它们免受人类上皮癌细胞系和癌症干细胞的一个面板。大多数新的GAEL类似物比苯丁酸氮芥，顺铂和沙利霉素更有效。最有效的基于双胺的GAEL类似物1，与β-GLN相比，图2，图4和图8显示出对各种癌细胞系的细胞毒性提高了2-3倍，这表明添加第二个氨基基团增强了细胞毒性作用。活性最高的GAEL 1和4对分离自乳腺癌（BT-474）和前列腺（DU-145）细胞系的癌症干细胞的影响表明，两种GAEL抑制肿瘤球的形成并导致> 95％的损失5μM时癌症干细胞的活力 GAEL 1对BT-474癌症干细胞的活性优于沙利霉素。
• Synthesis and selective anticancer activity of steroidal glycoconjugates
  作者：María A. Fernández-Herrera、Hugo López-Muñoz、José M.V. Hernández-Vázquez、Luis Sánchez-Sánchez、María L. Escobar-Sánchez、B. Mario Pinto、Jesús Sandoval-Ramírez

  DOI：10.1016/j.ejmech.2012.06.027

  日期：2012.8

  The synthesis of glucosamine derivatives of the steroidal sapogenins diosgenin and hecogenin using the N-phthaloyl protected trichloroacetimidate of d-glucosamine as donor and TMSOTf as promoter is reported. The corresponding glycoconjugates were transformed into their acetamido derivatives and the hydrochloride salt (from diosgenin) and tested against HeLa, CaSki, and ViBo cervicouterine cancer cells

  的葡糖胺衍生物的合成的甾体皂苷元薯蓣皂苷元和使用核柯配基Ñ -phthaloyl保护的三氯乙酰d葡糖胺作为供体和将TMSOTf作为启动子的报道。将相应的糖缀合物转化为其乙酰氨基衍生物和盐酸盐（来自薯os皂素），并针对HeLa，CaSki和ViBo宫颈外膜癌细胞进行测试。这些化合物对肿瘤细胞和人淋巴细胞显示出低细胞毒性值，表明主要的细胞死亡过程可能不是坏死。重要的是，这些化合物对肿瘤细胞的抗增殖活性并不影响外周血淋巴细胞的增殖潜能。
• Structure Activity Relationships of N-linked and Diglycosylated Glucosamine-Based Antitumor Glycerolipids
  作者：Makanjuola Ogunsina、Hangyi Pan、Pranati Samadder、Gilbert Arthur、Frank Schweizer

  DOI：10.3390/molecules181215288

  日期：——

  1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (1) was previously reported to show potent in vitro antitumor activity on a range of cancer cell lines derived from breast, pancreas and prostate cancer. This compound was not toxic to mice and was inactive against breast tumor xenografts in mice. This inactivity was attributed to hydrolysis of the glycosidic linkage by glycosidases. Here three N-linked (glycosylamide) analogs 2–4, one triazole-linked analog 5 of 1 as well as two diglycosylated analogs 6 and 7 with different stereochemistry at the C2-position of the glycerol moiety were synthesized and their antitumor activity against breast (JIMT-1, BT-474, MDA-MB-231), pancreas (MiaPaCa2) and prostrate (DU145, PC3) cancer cell lines was determined. The diglycosylated analogs 1-O-hexadecyl-2(R)-, 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (7) and the 1:1 diastereomeric mixture of 1-O-hexadecyl-2(R/S), 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (6) showed the most potent cytotoxic activity at CC50 values of 17.5 µM against PC3 cell lines. The replacement of the O-glycosidic linkage by a glycosylamide or a glycosyltriazole linkage showed little or no activity at highest concentration tested (30 µM), whereas the replacement of the glycerol moiety by triazole resulted in CC50 values in the range of 20 to 30 µM. In conclusion, the replacement of the O-glycosidic linkage by an N-glycosidic linkage or triazole-linkage resulted in about a two to three fold loss in activity, whereas the replacement of the methoxy group on the glycerol backbone by a second glucosamine moiety did not improve the activity. The stereochemistry at the C2-position of the glycero backbone has minimal effect on the anticancer activities of these diglycosylated analogs.

  据先前报道，1-O-十六烷基-2-O-甲基-3-O-(2'-氨基-2'-脱氧-β-D-吡喃葡萄糖基)-sn-甘油（1）对一系列来自乳腺癌、胰腺癌和前列腺癌的癌细胞系显示出强大的体外抗肿瘤活性。该化合物对小鼠无毒性，对小鼠乳腺肿瘤异种移植无活性。这种无效性是由于糖苷酶水解了糖苷键。在此，我们合成了三种 N-连接（糖基酰胺）类似物 2-4、一种 1 的三唑连接类似物 5 以及两种在甘油分子 C2 位上具有不同立体化学结构的二糖基化类似物 6 和 7，并测定了它们对乳腺癌（JIMT-1、BT-474、MDA-MB-231）、胰腺癌（MiaPaCa2）和前列腺癌（DU145、PC3）细胞系的抗肿瘤活性。二糖基化类似物 1-O-十六烷基-2(R)-, 3-O-二（2'-氨基-2'-脱氧-β-D-吡喃葡萄糖基）-sn-甘油（7）和 1：1-O-hexadecyl-2(R/S), 3-O-di-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol（6）的非对映异构体混合物显示出最强的细胞毒性活性，对 PC3 细胞株的 CC50 值为 17.5 µM。用糖酰胺或糖基三唑取代 O-糖苷键，在测试的最高浓度（30 µM）下活性很小或没有活性，而用三唑取代甘油分子，CC50 值在 20 至 30 µM 之间。总之，用 N-糖苷键或三唑键取代 O-糖苷键会导致活性降低约 2 到 3 倍，而用第二个氨基葡萄糖取代甘油骨架上的甲氧基不会提高活性。甘油骨架 C2 位的立体化学对这些二糖基化类似物的抗癌活性影响很小。