(2R,3R,4R,5S,6R)-2-(hydroxymethyl)-6-propylpiperidine-3,4,5-triol | 193270-40-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (2R,3R,4R,5S,6R)-2-(hydroxymethyl)-6-propylpiperidine-3,4,5-triol
• 英文别名: alpha-1-C-Propyl-DNJ
• CAS: 193270-40-5
• 化学式: C₉H₁₉NO₄
• 分子量: 205.254
• InChiKey: WUPMYSMCQJMDRE-SYHAXYEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  14
• 可旋转键数：
  3
• 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

• 作为产物：
  描述：

  2,3,4,6-四苄基-D-吡喃葡萄糖 在 palladium dihydroxide 哌啶 、 4 A molecular sieve 、 氢气 、 三乙酰氧基硼氢化钠 、 sodium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 sodium sulfate 、 pyridinium chlorochromate 作用下， 以 1,4-二氧六环 、 乙醚 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成 (2R,3R,4R,5S,6R)-2-(hydroxymethyl)-6-propylpiperidine-3,4,5-triol
  参考文献：
  名称：

  野尻霉素C-糖苷的合成新工艺

  摘要：

  由四苄基葡萄糖和苄胺得到的 N,2,3,4,6-戊苄基-D-吡喃葡萄糖胺 2 与烯丙基溴化镁反应，立体选择性地得到开链氨基醇 3，其通过完全反应转化为野尻霉素 6 的 C-糖苷。通过 Fmoc 保护氨基功能、游离羟基的氧化、Fmoc 基团的水解和最后用 NaBH(OAc)3 进行的分子内还原胺化；化合物 6 也通过操作烯丙基附属物转化为甲基酮 7。

  DOI：

  10.1039/b003877f

文献信息

• Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors
  作者：Davide Bini、Francesca Cardona、Matilde Forcella、Camilla Parmeggiani、Paolo Parenti、Francesco Nicotra、Laura Cipolla

  DOI：10.3762/bjoc.8.58

  日期：——

  A small set of nojirimycin- and pyrrolidine-based iminosugar derivatives has been synthesized and evaluated as potential inhibitors of porcine and insect trehalases. Compounds 12, 13 and 20 proved to be active against both insect and porcine trehalases with selectivity towards the insect glycosidase, while compounds 10, 14 and 16 behaved as inhibitors only of insect trehalase. Despite the fact that

  一小组基于野尻霉素和吡咯烷的亚氨基糖衍生物已被合成并评估为猪和昆虫海藻糖酶的潜在抑制剂。化合物 12、13 和 20 被证明对昆虫和猪海藻糖酶均具有活性，并且对昆虫糖苷酶具有选择性，而化合物 10、14 和 16 仅作为昆虫海藻糖酶的抑制剂。尽管在微摩尔范围内发现了活性，但这些发现可能有助于阐明此类不同来源的酶的结构特征，这些特征仍然很少被表征。
• α-1-C-Alkyl-1-deoxynojirimycin derivatives as potent and selective inhibitors of intestinal isomaltase: remarkable effect of the alkyl chain length on glycosidase inhibitory profile
  作者：Guillaume Godin、Philippe Compain、Olivier R. Martin、Kyoko Ikeda、Liang Yu、Naoki Asano

  DOI：10.1016/j.bmcl.2004.09.086

  日期：2004.12

  A series of alpha- and beta-1-C-alkyl-1-deoxynojirimycin derivatives was prepared and evaluated as glycosidase inhibitors. Biological assays showed a marked dependence of the selectivity and potency of the inhibitors upon the position of the alkyl chain (alpha-1-C-, beta-1-C- or N-alkyl derivatives). In addition, the efficiency of alpha-1-C-alkyl-1-deoxynojirimycin derivatives as intestinal isomaltase inhibitors increases with the length of the alkyl chain. The strongest inhibition was found for alpha-1-C-nonyl-1-deoxynojirimycin with an IC50 = 3.5 nM (25x more potent inhibitor than the shorter chain homologue carrying a C-8 chain). These results demonstrate that subtle changes in the aglycon fragment may result in remarkable enzyme specificity. (C) 2004 Elsevier Ltd. All rights reserved.
• MRNA BASED ENZYME REPLACEMENT THERAPY COMBINED WITH A PHARMACOLOGICAL CHAPERONE FOR THE TREATMENT OF LYSOSOMAL STORAGE DISORDERS
  申请人：ModernaTX, Inc.

  公开号：US20220184185A1

  公开（公告）日：2022-06-16

  This disclosure relates to treatment of lysosomal storage disorders, such as Fabry disease or Gaucher disease, with a combination treatment containing (i) an mRNA encoding a lysosomal enzyme deficient in the lysosomal storage disorder, and (ii) a compound that is a glucosylceramide synthase inhibitor or a pharmacological chaperone of the lysosomal enzyme. mRNAs for use in the invention, when administered in vivo, encode the enzyme that is deficient in the lysosomal storage disorder, functional fragments thereof (e.g., those comprising the catalytic domain), or fusion proteins containing the enzyme that is deficient in the lysosomal storage disorder. mRNA therapies can be used to increase and/or restore deficient levels of a lysosomal enzyme's expression and/or activity in subjects.