1,5-dideoxy-1,5-imino-L-allitol | 168960-10-9

• 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-dideoxy-1,5-imino-L-allitol
• 英文别名: (S)-1-deoxy-allonojirimycin；1-deoxy-L-allonojirimycin；L-1-deoxyallonojirimycin；(2S,3S,4R,5R)-2-(hydroxymethyl)piperidine-3,4,5-triol
• CAS: 168960-10-9
• 化学式: C₆H₁₃NO₄
• 分子量: 163.174
• InChiKey: LXBIFEVIBLOUGU-BGPJRJDNSA-N

物化性质

• 沸点：
  361.1±42.0 °C(Predicted)
• 密度：
  1.456±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  93
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-溴壬烷 、 1,5-dideoxy-1,5-imino-L-allitol 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,3S,4R,5R)-2-(hydroxymethyl)-1-nonylpiperidine-3,4,5-triol
  参考文献：
  名称：

  基于荧光偏振活性的蛋白质谱分析法在人类非溶酶体葡萄糖基神经酰胺酶的有效，选择性抑制剂的发现中。

  摘要：

  人非溶酶体葡萄糖基神经酰胺酶（GBA2）是控制糖脂水平的几种酶之一，其活性与几种人类疾病状态相关。迫切需要设计或发现选择性的GBA2抑制剂作为化学工具和潜在的治疗剂。在这里，我们描述了基于荧光偏振活性的蛋白质谱分析（FluoPol-ABPP）测定法的发展，该测定法可从350多种亚氨基糖文库中快速鉴定GBA2抑制剂。基于FluoPol-ABPP筛选的线索生成聚焦库，并针对与其他葡糖神经酰胺代谢酶，葡糖神经酰胺合酶（GCS），溶酶体葡糖神经酰胺酶（GBA）和胞质保留β-葡糖苷酶GBA3的GBA2选择性偏移进行评估。我们的工作产生了有效的和选择性的GBA2抑制剂，

  DOI：

  10.1021/jacs.7b07352
• 作为产物：
  描述：

  (-)-(2S,3R)-3-羟基-2-(羟甲基)-3,6-二氢-2H-吡啶-1-羧酸叔丁酯 在 吡啶 、 盐酸 、 potassium osmate(VI) 、 N-甲基吲哚酮 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 10.0h， 生成 1,5-dideoxy-1,5-imino-L-allitol
  参考文献：
  名称：

  Biological Properties of d- and l-1-Deoxyazasugars

  摘要：

  L-Enantiomers of 1-deoxynojirimycin (DNJ), 1-deoxymannojirimycin (manno-DNJ), 1-deoxyallonojirimycin (allo-DNJ), 1-deoxyaltronojirimycin (altro-DNJ), 1-deoxygalactonojirimycin (galacto-DNJ), 1-deoxygulonojirimycin (gulo-DNJ), and 1-deoxyldonojirimycin (ido-DNJ) were prepared according to prior methods for the D-enantiomers. These enantiospecific syntheses established unambiguously the absolute configuration of naturally occurring DNJ, manno-DNJ, allo-DNJ, altro-DNJ, and gulo-DNJ. Although D-DNJ and D-galacto-DNJ are known to be powerful competitive inhibitors of alpha-glucosidase and alpha-galactosidase, respectively, with K-i values in the nM range, L-DNJ and L-galacto-DNJ were noncompetitive inhibitors of alpha-glucosidase and alpha-galactosidase, respectively, with K-i values in the PM range. However, the azasugar mimicking the structure of the terminal sugar moiety of the natural substrate is not always an inhibitor of the glycosidase responsible for the hydrolysis. D-manno-DNJ is known as a much better inhibitor of alpha-L-fucosidase than a-mannosidase, while L-allo-DNJ was a better inhibitor than D-manno-DNJ of alpha-mannosidase. L-galacto-DNJ can be regarded as the 6-hydroxylated derivative of deoxyfuconojirimycin (DFJ), which is a powerful inhibitor of alpha-L-fucosidase with a K-i value in the nM range. However, this replacement of the methyl group in DFJ by a hydroxymethyl group reduced its affinity by about 50-fold. This suggests that there is a hydrophobic region in or around the active site of alpha-L-fucosidase. It has been found that inhibitors of human lysosomal glycosidases have therapeutic potential for the corresponding lysosomal storage diseases (Nat. Med. 1999, 5, 112; Proc. Natl. Acad. Sci. USA, 2002, 99, 15428). Inhibition of human lysosomal glycosidases by the 1-deoxyazasugars synthesized was investigated. D-galacto-DNJ is a potent inhibitor of lysosomal alpha-galactosidase (IC50 = 90 nM) and is now being evaluated preclinically for its potential use in Fabry disease, while D-DNJ inhibiting alpha-glucosidase (IC50 = 40 nM) potently does not appear to become a potential therapeutic agent because of additional inhibitory activity toward glycoprotein processing alpha-glucosidases. On the other hand, although L-allo-DNJ is a moderate inhibitor of alpha-mannosidase (IC50 = 64 mu M), it may become a key compound for the drug design of potential therapeutic agents for alpha-mannosidosis.

  DOI：

  10.1021/jm0495881

文献信息

• Phosphinic Acid/ <scp>NaI</scp> Mediated Reductive Cyclization Approach for Accessing the <scp> <i>L</i> ‐1‐Deoxynojirimycin </scp> Using a <scp>Two‐Component Three‐Centered</scp> ( <scp>2C3C</scp> ) Ugi Type Reaction
  作者：Chandra S Azad、Pratibha Shukla、Mark A Olson、Anudeep K Narula

  DOI：10.1002/cjoc.202000634

  日期：2021.6

  A catalytic two-component three-centered (2C3C) Ugi-type reaction was developed for the synthesis of L-1-deoxynojirimycin (DNJ) isomers using a chiron approach. This new and quite mild catalytic system, comprised of phenylphosphinic acid/NaI, was used to synthesize both the L-allo-DNJ and L-altro-DNJ in high yield.

  开发了一种催化两组分三中心（2C3C）Ugi型反应，用于使用Chiron方法合成L -1-脱氧野oji霉素（DNJ）异构体。这种由苯次膦酸/ NaI组成的新型且温和的催化体系用于高收率地合成L - allo -DNJ和L - altro -DNJ。
• Ring Enlargement of Polyhydroxylated Pyrrolidines to Piperidines by ­Mitsunobu Reaction: A Fortuitous Synthesis of 1-Deoxy-<scp>l</scp>-allonojirimycin
  作者：Alessandro Dondoni、Alberto Marra、Barbara Richichi、Daniela Perrone

  DOI：10.1055/s-2004-829566

  日期：——

  corresponding R-protected pyrrolidines and 2-deoxy-piperidines in different ratios depending on the stereochemistry of the starting pyrrolidine and the nature of the acid R-OH. A mechanistic scheme is proposed involving the formation of an aziridinium ion as an intermediate. A piperidine derivative obtained in 74% yield was converted in four steps into the title allonojirimycin.

  手性 3,4-二苄氧基-5-羟甲基-2-噻唑基吡咯烷在光延条件下（R-OH、Ph 3 P、DIAD in THF，80 °C）得到不同比例的相应 R-保护的吡咯烷和 2-脱氧-哌啶取决于起始吡咯烷的立体化学和酸 R-OH 的性质。提出了涉及形成氮丙啶鎓离子作为中间体的机制方案。以 74% 产率获得的哌啶衍生物分四步转化为标题别异野尻霉素。
• Efficient and stereodivergent synthesis of deoxyimino sugars
  作者：Bor-Cherng Hong、Zhong-Yi Chen、Arumugam Nagarajan、Rudresha Kottani、Vishal Chavan、Wei-Hung Chen、Yea-Fen Jiang、Shuo-Cang Zhang、Ju-Hsiou Liao、Sepehr Sarshar

  DOI：10.1016/j.carres.2005.08.014

  日期：2005.11

  Both cis- and trans-2-substituted-1,2,3,6-tetrahydro-pyridin-3-ols have been prepared via an aldol condensation-ring-closing metathesis sequence. A stereodivergent synthesis of optionally functionalized deoxyimino sugars was achieved via asymmetric dihydroxylation or epoxidation/nucleophilic substitution of these tetrahydropyridines. (C) 2005 Elsevier Ltd. All rights reserved.
• A general strategy for the stereoselective synthesis of l-1-deoxyallonojirimycin and d-1-deoxygulonojirimycin
  作者：Subhash Ghosh、J. Shashidhar、Samit Kumar Dutta

  DOI：10.1016/j.tetlet.2006.06.110

  日期：2006.8

  A general strategy for the synthesis of deoxyazasugars from D-glucose is described. Ring-closing metathesis and stereoselective dihydroxylation reactions were used as key steps. (c) 2006 Elsevier Ltd. All rights reserved.
• Stereocontrolled synthesis of 1,5-dideoxy-1,5-imino-allitol (1-deoxy-allonojirimycin) from serine
  作者：Hans-Josef Altenbach、Klaus Himmeldirk

  DOI：10.1016/0957-4166(95)00129-d

  日期：1995.5

  1-Deoxy-L-allonojirimycin was prepared from a protected L-serine aldehyde via a 5,6-dihydro-2-pyridone as a key intermediate.