tri-O-benzyl-2-deoxy-D-galactono-1,5-lactone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tri-O-benzyl-2-deoxy-D-galactono-1,5-lactone
• 英文别名: (2R,3R,4R)-3,4-bis-benzyloxy-2-benzyloxymethyltetrahydropyran-5-one；3,4,6-tri-O-benzyl-2-deoxy-D-lyxo-hexono-1,5-lactone；(4R,5R,6R)-4,5-Bis(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one；(4R,5R,6R)-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-one
• 化学式: C₂₇H₂₈O₅
• 分子量: 432.516
• InChiKey: XDRGBAJBRHEMCV-RGSZASNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tri-O-benzyl-2-deoxy-D-galactono-1,5-lactone 在 palladium on activated charcoal N-溴代丁二酰亚胺(NBS) 、 氢气 、 双(三甲基硅烷基)氨基钾 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 methyl (2R,4R,5R,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-methoxyoxane-2-carboxylate
  参考文献：
  名称：

  由糖内酯的乙烯酮二硫缩醛的首次合成：方便地获得3-ulosonic酸

  摘要：

  异构的2-脱氧醛内酯与2- [双（2,2,2-三氟乙氧基）磷酰基] 1,3-二硫杂环丁烷进行霍纳-埃蒙反应，得到相应的烯酮二硫缩醛，它们是合成3-的关键中间体脱氧-2-酮-醛糖酸。

  DOI：

  10.1016/s0040-4039(98)01045-4
• 作为产物：
  描述：

  (2R,3R,4R)-2-(羟基甲基)-3,4-二氢-2H-吡喃-3,4-二醇 在 盐酸 、 sodium hydride 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 生成 tri-O-benzyl-2-deoxy-D-galactono-1,5-lactone
  参考文献：
  名称：

  Glycomimetic Ligands for the Human Asialoglycoprotein Receptor

  摘要：

  The asialoglycoprotein receptor (ASGPR) is a high-capacity galactose-binding receptor expressed on hepatocytes that binds its native substrates with low affinity. More potent ligands are of interest for hepatic delivery of therapeutic agents. We report several classes of galactosyl analogues with varied substitution at the anomeric, C2-, C5-, and C6-positions. Significant increases in binding affinity were noted for several trifluoromethyl-acetamide derivatives without covalent attachment to the protein. A variety of new ligands were obtained with affinity for ASGPR as good as or better than that of the parent N-acetylgalactosamine, showing that modification on either side of the key C3,C4-diol moiety is well tolerated, consistent with previous models of a shallow binding pocket. The galactosyl pyranose motif therefore offers many opportunities for the attachment of other functional units or payloads while retaining low-micromolar or better affinity for the ASGPR.

  DOI：

  10.1021/ja2104679

文献信息

• Illuminating the binding interactions of galactonoamidines during the inhibition of β-galactosidase (E. coli)
  作者：Qiu-Hua Fan、Jessica B. Pickens、Susanne Striegler、Cédric D. Gervaise

  DOI：10.1016/j.bmc.2015.12.034

  日期：2016.2

  identified as very potent competitive inhibitors that exhibit stabilizing hydrophobic interactions of the aglycon in the active site of β-galactosidase (Aspergillus oryzae). To elucidate the contributions of the glycon to the overall inhibition ability of the compounds, three glyconoamidine derivatives with alteration in the glycon at C-2 and C-4 were synthesized and evaluated herein. All amidines are competitive

  先前已鉴定出几种半乳糖酰胺是非常有效的竞争性抑制剂，在β-半乳糖苷酶（米曲霉）的活性位点中，糖苷配基具有稳定的疏水相互作用。为了阐明糖苷对化合物总体抑制能力的贡献，在本文中合成并评估了三种在C-2和C-4的糖苷具有改变的糖胺no衍生物。所有am都是β-半乳糖苷酶（大肠杆菌）的竞争性抑制剂。），并且与亲本相比显示出明显降低的抑制能力。结果突出了the糖苷C-2处的羟基与酶的活性位点之间强烈的氢键相互作用。稍弱的H键通过C-4处的羟基促进。对于母体半乳糖o而言，抑制常数确定为皮摩尔，对于所设计的衍生物而言，纳摩尔浓度为纳摩尔浓度，从而使所有糖基very都成为糖苷酶的强效抑制剂，尽管衍生化的show的抑制活性比母体低700倍。
• [EN] TARGETED BIFUNCTIONAL DEGRADERS<br/>[FR] AGENTS DE DÉGRADATION BIFONCTIONNELS CIBLÉS
  申请人：UNIV YALE

  公开号：WO2021072269A1

  公开（公告）日：2021-04-15

  The present invention provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In another aspect, the present invention provides bifunctional compounds that can be used to promote or enhance degradation of certain autoantibodies. In certain embodiments, treatment or management of a disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein or the autoantibody in the subject. Thus, in certain embodiments, administration of a compound of the invention to the subject removes or reduces the circulation concentration of the circulating protein or the autoantibody, thus treating, ameliorating, or preventing the disease and/or disorder. In certain embodiments, the circulating protein is TNF.

  本发明在一个方面提供了可以用来促进或增强降解某些循环蛋白的双功能化合物。在另一个方面，本发明提供了可以用来促进或增强降解某些自身抗体的双功能化合物。在某些实施方式中，治疗或管理疾病和/或疾病需要降解、去除或减少受试者体内循环蛋白或自身抗体的浓度。因此，在某些实施方式中，将本发明的化合物给予受试者可去除或减少循环蛋白或自身抗体的循环浓度，从而治疗、改善或预防疾病和/或疾病。在某些实施方式中，循环蛋白是TNF。
• [EN] ENGINEERED ANTIBODIES AS MOLECULAR DEGRADERS THROUGH CELLULAR RECEPTORS<br/>[FR] ANTICORPS CONÇUS COMME AGENTS DE DÉGRADATION MOLÉCULAIRE PAR L'INTERMÉDIAIRE DE RÉCEPTEURS CELLULAIRES
  申请人：UNIV YALE

  公开号：WO2021072246A1

  公开（公告）日：2021-04-15

  The present disclosure provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In certain embodiments, the circulating protein mediates a disease and/or disorder in a subject, and treatment or management of the disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein in the subject. Thus, in certain embodiments, administration of a compound of the disclosure to the subject removes or reduces the circulation concentration of the circulating protein, thus treating, ameliorating, or preventing the disease and/or disorder.

  本公开提供了一种双功能化合物，可用于促进或增强特定循环蛋白的降解。在某些实施例中，循环蛋白在受试者中介导疾病和/或紊乱，治疗或管理该疾病和/或紊乱需要降解、去除或减少受试者中循环蛋白的浓度。因此，在某些实施例中，将本公开的化合物给予受试者可去除或减少循环蛋白的循环浓度，从而治疗、改善或预防疾病和/或紊乱。
• Glycal-mediated syntheses of enantiomerically pure polyhydroxylated γ- and δ-lactams
  作者：Antonella Squarcia、Fabrizio Vivolo、Hans-Georg Weinig、Pietro Passacantilli、Giovanni Piancatelli

  DOI：10.1016/s0040-4039(02)00852-3

  日期：2002.5

  Syntheses of new enantiomerically pure γ-lactams 4a,b and δ-lactams 5a,b from d-glucal (3a) and d-galactal (3b) as starting materials are described.

  描述了以d-葡萄糖（3a）和d-半乳糖（3b）为原料合成新的对映体纯的γ-内酰胺4a，b和δ-内酰胺5a，b。
• Synthetic routes to methyl 3-deoxy-aldulosonic acid methyl esters and their 2-deoxy isomers based on the Horner-Emmons and Peterson reaction of sugar lactones
  作者：Jacek Młynarski、Anna Banaszek

  DOI：10.1016/s0040-4020(99)00049-6

  日期：1999.2

  The two reagents: 2-trimethylsilyl- and 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]-1,3-dithianes were engaged in the construction of appropriate ketene thioacetals from the isomeric 2-deoxy-hexono-1,5-lactones via Horner-Emmons or Peterson reaction. A comparison of the results shows that the second reagent is more promising, as it forms the desired ketene thioacetals as sole products. The latter were

  将两种试剂：2-三甲基甲硅烷基-和2- [双（2,2,2-三氟乙氧基）磷酰基] -1,3-二硫杂环丁烷用于从异构的2-脱氧六邻体-1构建合适的乙烯酮硫缩醛，通过霍纳-埃蒙斯或彼得森反应生成5-内酯。结果的比较表明，第二种试剂更有前景，因为它形成了所需的烯酮硫缩醛作为唯一产物。使用NBS / MeOH在CH 2 Cl 2中，通过氧化水解反应将后者直接立体选择性转化为标题αulosonates 。2-脱氧-磺基甲酸甲酯的构建涉及先前通过LiBH 4 -TMSCl物种对双键的氢化，以及随后在THF水溶液中用NBS水解。