2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-galactono-1,5-lactone | 160701-84-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-galactono-1,5-lactone
• 英文别名: (3R,4R,5R,6R)-3-azido-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-one；(3R,4R,5R,6R)-3-azido-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-one
• CAS: 160701-84-8
• 化学式: C₂₇H₂₇N₃O₅
• 分子量: 473.528
• InChiKey: JZVINQNAXZEQKZ-FXSWLTOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-galactono-1,5-lactone 在 三乙基硅烷 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 1.08h， 生成 p-methoxyphenyl-tri-O-benzyl-2-azido-2-deoxy-D-galactopyranoside
  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
• 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 、 双(三甲基硅烷基)氨基钾 、 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 、 甲苯 为溶剂， 反应 28.83h， 生成 2-azido-3,4,6-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

• [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。
• Expeditious Synthesis of β-Linked Glycosyl Serine Methylene Isosteres (β-C-Gly Ser) via Ethynylation of Sugar Lactones
  作者：Alessandro Dondoni、Giandomenico Mariotti、Alberto Marra、Alessandro Massi

  DOI：10.1055/s-2001-18058

  日期：——

  The addition of the lithium derivative of N-Boc 4-ethynyl-2,2-dimethyl-1,3-oxazolidine to tetra-O-benzyl-d-gluco- and galactonolactone and 2-azido-2-deoxy congeners afforded the corresponding ethynyl ketoses in fairly good yields (64-78%). Following the conversion of the ketoses into O-acetates and removal of the acetoxy group by silane reduction, the resulting β-linked ethynyl glycosides were transformed into N-Boc C-glycosyl α-aminobutyric acids by reduction of the triple bond using H2/Pd(OH)2 and oxidative cleavage of the oxazolidine ring using the Jones’ reagent. After the removal of O-benzyl groups of the carbohydrate moieties by hydrogenation and the reduction of azido to amino group, all compounds were subjected to acetylation and isolated as O- and N-acetyl derivatives. The C-glycosyl α-amino acids prepared correspond to methylene isosteres of O-glycosyl serines.

  将N-Boc 4-乙炔基-2,2-二甲基-1,3-噁唑烷的锂衍生物与四-O-苄基-d-葡萄糖和d-半乳糖内酯以及2-叠氮-2-脱氧同系物反应，得到相应的乙炔基酮，产率相当不错（64-78%）。在将酮转化为O-醋酸酯并通过硅烷还原去除醋酸氧基后，得到的β-连接乙炔基糖苷通过使用H2/Pd(OH)2还原三重键和利用琼斯试剂氧化开环将噁唑烷环转化为N-Boc C-糖苷 α-氨基丁酸。在通过氢化去除糖部分的O-苄基后，并将叠氮基还原为氨基后，所有化合物均经过醋酸化处理，并以O-和N-醋酸衍生物的形式分离出来。所制备的C-糖苷 α-氨基酸对应于O-糖苷丝氨酸的亚甲基等构体。
• Electrophilic azidation of 2-deoxy-aldono-1,5-lactones: an alternative route to 2-azido-2-deoxy-aldopyranoses
  作者：Fran�ois-Yves Dupradeau、Sen-itiroh Hakomori、Tatsushi Toyokuni

  DOI：10.1039/c39950000221

  日期：——

  Electrophilic azidation of tri-O-benzyl-2-deoxy-D-galactono-1,5-lactone 3 with triisopropylphenylsulfonyl azide, followed by selective reduction with diisobutylaluminium hydride, yielded tri-O-benzyl-2-azido-2-deoxy-D-galactopyranose 5 as the sole product in 80% yield, while the same sequence of reactions with the 2-deoxy-glucono-1,5-lactone derivative 8 afforded only tri-O-benzyl-2-azido-2-deoxy-D-mannopyranose 10 in 65% yield.

  三-O-苄基-2-脱氧-D-半乳糖醛-1,5-内酯3与三异丙基苯磺酰叠氮化物的电亲核叠氮化反应，随后使用二异丁基铝氢化物进行选择性还原，得到了三-O-苄基-2-叠氮-2-脱氧-D-半乳糖吡喃糖5，产率为80%，而对2-脱氧-D-葡萄糖醛-1,5-内酯衍生物8进行相同的反应顺序仅得到三-O-苄基-2-叠氮-2-脱氧-D-甘露糖吡喃糖10，产率为65%。
• [EN] BIFUNCTIONAL SMALL MOLECULES TO TARGET THE SELECTIVE DEGRADATION OF CIRCULATING PROTEINS<br/>[FR] PETITES MOLÉCULES BIFONCTIONNELLES POUR CIBLER LA DÉGRADATION SÉLECTIVE DE PROTÉINES CIRCULANTES
  申请人：UNIV YALE

  公开号：WO2019199634A4

  公开（公告）日：2019-12-05