1,5,6-trideoxy-1,5-imino-D-glucitol | 73861-92-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1,5,6-trideoxy-1,5-imino-D-glucitol
• 英文别名: 1,6-dideoxynojirimycin；(2R,3R,4R,5S)-2-methylpiperidine-3,4,5-triol
• CAS: 73861-92-4
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: VYOCYWDJTQRZLC-JGWLITMVSA-N

物化性质

• 沸点：
  280.2±40.0 °C(Predicted)
• 密度：
  1.297±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  72.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,5,6-trideoxy-1,5-imino-D-glucitol 在 palladium on activated charcoal 氢气 、 双氧水 作用下， 以 甲醇 、 水 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 96.0h， 生成 N-methyl-1,6-dideoxynojirimycin oxide
  参考文献：
  名称：

  Enzyme-catalyzed aldol condensation for asymmetric synthesis of azasugars: synthesis, evaluation, and modeling of glycosidase inhibitors

  摘要：

  A combined fructose 1,6-diphosphate aldolase reaction and catalytic reductive amination has been used in the asymmetric synthesis of azasugars structurally corresponding to N-acetylglucosamine, N-acetylmannosamine, and deoxyhexoses. The 6-deoxyazasugars were prepared by direct hydrogenolysis of the aldolase product without removal of the 6-phosphate group. Both (R)- and (S)-3-azido-2-acetamidopropanal used as substrates in the aldolase reactions were prepared from the corresponding lipase-resolved 2-hydroxy species followed by formation of an aziridine intermediate and opening of the aziridine with azide. Evaluation of these azasugars and their diastereomerically pure tertiary amine oxides as well as 5-thioglucose and its sulfoxide derivatives as glycosidase inhibitors was carried out. It was found that all synthetic azasugars and 5-thioglucose were strong inhibitors, but oxidation of the ring heteroatom weakened the inhibition. With the aid of molecular modeling and inhibition analysis, a structure-K(i) relation of inhibitors was established which provides useful information for the design of new glycosidase inhibitors.

  DOI：

  10.1021/ja00016a039
• 作为产物：
  描述：

  2,3-O-(1-甲基乙亚基)-alpha-L-呋喃山梨糖 在 palladium dihydroxide 吡啶 、 sodium azide 、 Dowex 50(H+) 、 氢气 、 potassium carbonate 、 sodium iodide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0~110.0 ℃ 、413.68 kPa 条件下， 反应 100.0h， 生成 1,5,6-trideoxy-1,5-imino-D-glucitol
  参考文献：
  名称：

  A facile synthesis of 1,6-dideoxynojirimycin from l-sorbose

  摘要：

  A practical synthesis of 1,6-dideoxynojirimycin, a potent glycosidase inhibitor, starting from L-sorbose, is described. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2006.06.002

文献信息

• A general approach to the synthesis of dideoxy and trideoxyiminoalditols from β-d-glycosides
  作者：Gabriela Pistia、Rawle I. Hollingsworth

  DOI：10.1016/s0008-6215(00)00124-5

  日期：2000.10

  Imino sugars (also called azasugars), a class of compounds of which the 1,5-dideoxy and 1,5,6-trideoxyiminoalditols are members, are important glycosidase inhibitors with very high potential as drugs. Their potential therapeutic applications range from the treatment of diabetes to cancer and AIDS. We present here a general method for the preparation of such compounds with the D-gluco and D-galacto

  氨基糖（也称为氮杂糖）是一类重要的糖苷酶抑制剂，具有作为药物的巨大潜力，其中一类化合物的1，5-二甲氧基和1，5，6-三甲氧基亚氨基醛糖醇是其中的一员。它们的潜在治疗应用范围从糖尿病到癌症和艾滋病。我们在这里提出了一种从β-D-糖苷开始制备具有D-葡萄糖和D-半乳糖构型的化合物的一般方法。该方法特别具有吸引力，因为它具有很高的立体选择性和直接性。关键步骤是将糖苷选择性氧化为己磺酸，并将肟衍生物还原为内酰胺，然后将其进一步还原为目标化合物。如果C-6位带有乙酰氧基，则可以在还原过程中将其脱氧。然后产生三脱氧亚氨基糖。肟还原前的脱乙酰基产生双脱氧化合物。
• Organocatalytic<i>syn</i>-Aldol Reactions of Hydroxy Ketones with (<i>S</i>)-Isoserinal: Asymmetric Synthesis of 6-Deoxy-1,5-iminohexitols and Related Compounds
  作者：Cyril Nicolas、Roman Pluta、Monika Pasternak-Suder、Olivier R. Martin、Jacek Mlynarski

  DOI：10.1002/ejoc.201201413

  日期：2013.3

  intermediate was reacted through organocatalyzed aldol reaction or Wittig based chain extension and functionalization to give enantiopure 1,5,6-trideoxy-1,5-imino-hexitols such as 10a (L-manno) and 10b (D-gluco). These two compounds are of interest as glycosidase inhibitors. The elaborated organocatalytic process includes diastereoselective syn aldol reaction of (S)-isoserinal hydrate and hydroxyacetone or

  报道了一种改进且方便的大规模保护 (S)-异丝氨酸制备方法。该关键中间体通过有机催化的羟醛反应或基于 Wittig 的扩链和官能化反应，得到对映体纯的 1,5,6-trideoxy-1,5-imino-hexitols，如 10a (L-manno) 和 10b (D-gluco)。这两种化合物可用作糖苷酶抑制剂。精心设计的有机催化过程包括 (S)-异丝氨酸水合物与羟基丙酮或 1-羟基-2-辛酮的非对映选择性合成羟醛反应，并由各种基于氨基酸的催化剂促进。实现了高达 8:1 的非对映选择性，从而为这些重要的碳水化合物模拟物建立了一条新的、有效的合成路线。
• Synthesis of 1,6-Dideoxynojirimycin, 1,6-Dideoxy-D-allo-nojirimycin, and 1,6-Dideoxy-D-gulo-nojirimycinvia Asymmetric Hetero-Diels-Alder Reactions
  作者：Albert Defoin、Herv� Sarazin、Jacques Streith

  DOI：10.1002/hlca.19960790223

  日期：1996.3.20

  Asymmetric Diels-Alder reaction of sorbaldehyde O-methyloxime 1d with chiral chloronitroso derivative 2 of D-mannose, followed by osmylation of the primary cycloadduct, led to diol 6a with excellent enantioselectivity (ee > 99%; Scheme 1). Catalytic hydrogenolysis of 6a gave 1,6-dideoxy-D-allo-nojirimycin (7a). Nucleophilic ring opening of cyclic sulfate 8 allowed a straightforward synthesis of 1,

  不对称狄尔斯-阿尔德反应而山梨醛ö甲基肟1D与手性chloronitroso衍生物2 d甘露糖，接着由主环加成的锇酸酯化，导致二醇6A具有优异的对映选择性（ee值> 99％;方案1）。的催化氢解6A得到1,6-二脱氧D-同种异体-nojirimycin（图7a）。环状硫酸盐8的亲核开环允许直接合成1,6-二脱氧野oji霉素（11）和1,6-二脱氧-D-古洛基-野oji霉素（12；方案2）。
• ADJUVANT COMPOSITIONS
  申请人：Nash Robert James

  公开号：US20090047306A1

  公开（公告）日：2009-02-19

  An adjuvant composition comprises a Th1-activating alkaloid, optionally further comprising an auxiliary adjuvant selected from a type 2 adjuvant (e.g. alum and/or MF59), a type 1 adjuvant and/or a balanced adjuvant. Vaccines comprising the adjuvant composition include nucleic acid(s) which encode one or more antigenic protein(s); protein(s) or peptide(s); glycoprotein(s); polysaccharide(s) (e.g. carbohydrate(s)); fusion protein(s); lipid(s); glycolipid(s); peptide mimic(s) of polysaccharides carbohydrate(s) and a protein(s) in admixture; carbohydrate-protein conjugate(s); cells or extracts thereof; dead or attenuated cells or extracts thereof; tumour cells or extracts thereof; viral particles (e.g. attenuated viral particles or viral components); allergen(s) mixtures thereof.

  一种佐剂组合物包括一种Th1激活生物碱，可选地进一步包括一种辅助佐剂，所述辅助佐剂选自第2型佐剂（例如明胶和/或MF59）、第1型佐剂和/或平衡佐剂。包含该佐剂组合物的疫苗包括编码一种或多种抗原蛋白的核酸；蛋白质或肽；糖蛋白；多糖（例如碳水化合物）；融合蛋白；脂质；糖脂；多糖碳水化合物和蛋白质的肽类模拟物；糖蛋白-蛋白质结合物；细胞或其提取物；死细胞或其提取物；肿瘤细胞或其提取物；病毒颗粒（例如弱毒病毒颗粒或病毒成分）；过敏原或其混合物。
• IMMUNOMODULATORY ALKALOIDS
  申请人：Nash Robert James

  公开号：US20090117083A1

  公开（公告）日：2009-05-07

  Immunotherapy comprises administration of an alkaloid at a dose sufficient to induce IL-2 production in dendritic cells in a patient. The alkaloid induces the production of IL-2 in dendritic cells. The alkaloids need not be naturally occurring, and may be synthetic analogues or derivatives of naturally occurring counterparts. Such analogues or derivatives are preferably pharmaceutically acceptable analogues, salts, isomers or derivatives as herein defined. However, preferred alkaloids are phytochemicals. Such phytochemicals may be isolated from natural sources or synthesised in vitro. Particularly preferred are alkaloids is selected from piperidine alkaloids; pyrrolin alkaloids; pyrrolidine alkaloids; pyrolizidine alkaloids: indolizidine alkaloids and nortropane alkaloids.

  免疫疗法包括在患者体内以足够剂量给予一种生物碱，以诱导树突状细胞产生IL-2。这种生物碱会引起树突状细胞产生IL-2。这些生物碱不一定是天然存在的，也可以是天然存在的衍生物或合成类似物。这些类似物或衍生物最好是药学上可接受的类似物、盐、异构体或衍生物，如本文所定义。然而，最好的生物碱是植物化学物质。这些植物化学物质可以从天然来源中分离出来，也可以在体外合成。特别优选的生物碱包括吡啶生物碱、吡咯烷生物碱、吡咯烷生物碱、吡咯菊烷生物碱、吲哚菊烷生物碱和诺滕烷生物碱。