(-)-6-cyano-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose | 56760-91-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧吡喃
• 英文名称: (-)-6-cyano-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose
• 英文别名: 6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galacto-heptopyranurononitrile；1,2:3,4-di-O-isopropylidene-6-deoxy-6-galactopyranosiduronitrile；6-cyano-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranoside；2-((3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxolo)[4,5-b:4',5'-d]pyran-5-yl)acetonitrile；2-[(1S,2R,6R,8R,9S)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.02,6]dodecan-8-yl]acetonitrile
• CAS: 56760-91-9
• 化学式: C₁₃H₁₉NO₅
• 分子量: 269.298
• InChiKey: YOKIIWQBNZNEJI-ZKKRXERASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  69.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (-)-6-cyano-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 以66.3%的产率得到5-[6'-deoxy-(1',2':3',4'-di-O-isopropylidene-α-D-galactopyranos-6'-yl)]tetrazole
  参考文献：
  名称：

  Synthesis of New Five Membered Nitrogen Containing Heterocycles Bearing D-Galactose Side Chains

  摘要：

  The synthesis of 5-[6'-deoxy-(1',2':3',4'-di-O- isopropylidene-alpha -D-galactopyranos-6'-yl)]tetrazole and its reaction with acetic anhydride and 1,2:3,4-di-O-isopropylidene-6-O-(4-toluenesulfonyl)-alpha -D-galactopyranose are described.

  DOI：

  10.1080/00397910008087059
• 作为产物：
  描述：

  D-吡喃葡萄糖 在 咪唑 、 18-冠醚-6 、 硫酸 、 碘 、 copper(II) sulfate 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 4.0h， 生成 (-)-6-cyano-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose
  参考文献：
  名称：

  Synthesis of New Five Membered Nitrogen Containing Heterocycles Bearing D-Galactose Side Chains

  摘要：

  The synthesis of 5-[6'-deoxy-(1',2':3',4'-di-O- isopropylidene-alpha -D-galactopyranos-6'-yl)]tetrazole and its reaction with acetic anhydride and 1,2:3,4-di-O-isopropylidene-6-O-(4-toluenesulfonyl)-alpha -D-galactopyranose are described.

  DOI：

  10.1080/00397910008087059

文献信息

• Synthesis of amino-substituted hexo- and heptopyranoses from d-galactose
  作者：Benedikt Streicher、Bernhard Wünsch

  DOI：10.1016/s0008-6215(03)00382-3

  日期：2003.10

  After condensation of D-galactose with two equivalents of acetone, the last free hydroxy group was transformed into an acylated amino group by Swern oxidation, oxime formation, LiAlH4 reduction and acylation. The intermediate aldehyde was homologated with the Wittig reagent, (methoxymethyl)triphenylphosphonium chloride, to afford, after careful hydrolysis, a homologous heptodialdo-1,5-pyranose. Condensation

  D-半乳糖与两当量的丙酮缩合后，最后的游离羟基通过Swern氧化，肟形成，LiAlH4还原和酰化作用转变为酰化氨基。用Wittig试剂氯化（甲氧基甲基）三苯基phosph将中间体醛均化，在仔细水解后得到同源的庚二醛-1，5-吡喃糖。醛与羟胺的缩合和随后的LiAlH4还原提供了一个双-O，O-异亚丙基保护的7-氨基-6,7-二脱氧半乳糖庚基吡喃糖，其被各种羧酸衍生物酰化。通过仔细的水解或醇解作用裂解异亚丙基保护基团，得到6-酰基氨基-6-脱氧半乳糖吡喃糖和7-酰基氨基-6,7-二脱氧半乳糖庚基-吡喃糖。
• New Synthetic Technology for the Mild and Selective One-Carbon Homologation of Hindered Aldehydes in the Presence of Ketones
  作者：K. C. Nicolaou、Georgios Vassilikogiannakis、Remo Kranich、Phil S. Baran、Yong-Li Zhong、Swaminathan Natarajan

  DOI：10.1021/ol000102u

  日期：2000.6.1

  efficient method has been uncovered during the total synthesis of the CP molecules to accomplish the one-carbon homologation of sterically hindered aldehydes in the presence of acid- and base-labile moieties, Michael acceptors, and even other carbonyl groups such as reactive and epimerizable ketones. Mechanistic studies have revealed a neutral reagent for the rapid collapse of cyanohydrins to ketones.

  在CP分子的全合成过程中，发现了一种选择性，温和且高效的方法，可在酸和碱不稳定的基团，迈克尔受体甚至其他羰基化合物的存在下完成位阻醛的一碳同系化基团，例如反应性和差向异构的酮。机理研究表明，中性试剂可将氰醇快速分解为酮。
• The New Pharmacological Chaperones PBXs Increase α-Galactosidase A Activity in Fabry Disease Cellular Models
  作者：Pedro Besada、María Gallardo-Gómez、Tania Pérez-Márquez、Lucía Patiño-Álvarez、Sergio Pantano、Carlos Silva-López、Carmen Terán、Ana Arévalo-Gómez、Aurora Ruz-Zafra、Julián Fernández-Martín、Saida Ortolano

  DOI：10.3390/biom11121856

  日期：——

  Fabry disease is an X-linked multisystemic disorder caused by the impairment of lysosomal α-Galactosidase A, which leads to the progressive accumulation of glycosphingolipids and to defective lysosomal metabolism. Currently, Fabry disease is treated by enzyme replacement therapy or the orally administrated pharmacological chaperone Migalastat. Both therapeutic strategies present limitations, since enzyme replacement therapy has shown low half-life and bioavailability, while Migalastat is only approved for patients with specific mutations. The aim of this work was to assess the efficacy of PBX galactose analogues to stabilize α-Galactosidase A and therefore evaluate their potential use in Fabry patients with mutations that are not amenable to the treatment with Migalastat. We demonstrated that PBX compounds are safe and effective concerning stabilization of α-Galactosidase A in relevant cellular models of the disease, as assessed by enzymatic activity measurements, molecular modelling, and cell viability assays. This experimental evidence suggests that PBX compounds are promising candidates for the treatment of Fabry disease caused by mutations which affect the folding of α-Galactosidase A, even for GLA variants that are not amenable to the treatment with Migalastat.

  法布里病是一种X连锁多系统障碍，由溶酶体α-半乳糖苷酶A的损伤引起，导致糖脂代谢的进行受到影响和逐渐积累。目前，法布里病的治疗方法包括酶替代疗法和口服药物Migalastat。这两种治疗策略都存在局限性，因为酶替代疗法的半衰期和生物利用度较低，而Migalastat只适用于特定基因突变的患者。本研究的目的是评估PBX半乳糖类似物稳定α-半乳糖苷酶A的功效，从而评估它们在无法使用Migalastat治疗的法布里病患者中的潜在用途。我们证明PBX化合物在疾病相关细胞模型中稳定α-半乳糖苷酶A是安全和有效的，通过酶活性测量、分子建模和细胞存活率检测进行评估。这些实验证据表明，PBX化合物是治疗因α-半乳糖苷酶A折叠受影响而引起的法布里病的有希望的候选药物，即使对于不适用于Migalastat治疗的GLA变异体也是如此。
• Radical Decarboxylative Cyanomethylation of Aliphatic Carboxylic Acids and Uronic Acids via Vinyl Azide Cascade Fragmentation
  作者：Linhua Xu、Qishuai Li、Dongwei Li、Xin Zhou、Ni Song、Peng Wang、Ming Li

  DOI：10.1002/cjoc.202200732

  日期：——

  A direct oxidative radical decarboxylative cyanomethylation of carboxylic acids is described using 3-azido-2-methylbut-3-en-2-ol as the carbon-centered radical acceptor. The transformation is applicable to structurally diverse α-amino acids, α-oxy acids, α-keto acids, pentofuranuronic acids, and hexopyranuronic acids. The mechanistic investigations suggest that a radical process is involved in the

  使用 3-azido-2-methylbut-3-en-2-ol 作为以碳为中心的自由基受体，描述了羧酸的直接氧化自由基脱羧氰甲基化。该转化适用于结构多样的α-氨基酸、α-含氧酸、α-酮酸、戊呋喃糖醛酸和己吡喃糖醛酸。机械研究表明，转变涉及一个激进的过程。这项工作为构建具有生物学相关性的β-氨基酸、5-脱氧-己呋喃糖和 6-脱氧-庚糖提供了一种潜在的方法。
• 10.1021/acs.orglett.4c01016
  作者：Odoh, Amaechi Shedrack、Keeler, Courtney、Kim, Byoungmoo

  DOI：10.1021/acs.orglett.4c01016

  日期：——

  We introduce a new use of sulfonyl fluoride as a bifunctional reagent that facilitates the one-step deoxy-diversification of complex alcohol libraries. Our reaction design features a Sulfur(VI) Fluoride Exchange (SuFEx) mediated activation of alcohols and fluoride-induced activation of silicon-bound nucleophiles. This method enables the direct conversion of alcoholic C–O bonds in complex molecules into

  我们介绍了磺酰氟作为双功能试剂的一种新用途，可促进复杂醇库的一步脱氧多样化。我们的反应设计采用硫 (VI) 氟化物交换 (SuFEx) 介导的醇活化和氟化物诱导的硅结合亲核试剂活化。该方法能够通过 C-C、C-N、C-Cl 和 C-Br 键的形成将复杂分子中的醇 C-O 键直接转化为不同的类似物，同时抑制任何消除副产物。