(3R,4R,5R)-3-(β-D-glucopyranosyl)oxy-4-hydroxy-5-(hydroxymethyl)piperidine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3R,4R,5R)-3-(β-D-glucopyranosyl)oxy-4-hydroxy-5-(hydroxymethyl)piperidine
• 英文别名: (3R,4R,5R)-3-(β-D-glucopyranosyloxy)-5-(hydroxymethyl)-piperidin-4-ol；3-O-β-D-glucopyranosylisofagomine；3-O-(β-D-glucopyranosyl)isofagomine；Glucose beta-1,3-isofagamine；(2R,3R,4S,5S,6R)-2-[(3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)piperidin-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol
• 化学式: C₁₂H₂₃NO₈
• 分子量: 309.317
• InChiKey: BEXVSXHKIARRKH-FYKVHUBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  152
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (3R,4R,5R)-N-benzyloxycarbonyl-3,4-dihydroxy-5-(hydroxymethyl)piperidine 在 4 A molecular sieve 、 camphor-10-sulfonic acid 、 溶剂黄146 作用下， 以 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 9.5h， 生成 (3R,4R,5R)-3-(β-D-glucopyranosyl)oxy-4-hydroxy-5-(hydroxymethyl)piperidine
  参考文献：
  名称：

  1,3-β-D-葡聚糖内切水解酶的强效抑制剂 3-O-(β-D-Glucopyranosyl)-和 3-O-(β-Laminaribiosyl)-isofagomines 的合成

  摘要：

  4,6-O-亚苄基-N-苄氧基羰基异法戈明与 D-葡糖基和海带-二糖基三氯乙酰亚胺酯的糖基化在去除保护基后得到 3-O-(β-D-吡喃葡萄糖基)-和 3-O -(β-海带核糖基)-异法戈明。还包括相关四氢恶嗪的类似糖基化。3-O-(β-D-Glucopyranosyl)- 和 3-O-(β-海带核糖基)-isofagomines 是大麦 1,3-β-D-葡聚糖内切水解酶的有效抑制剂，ID50 值为 7.8 和分别为 3.1 μM。

  DOI：

  10.1071/ch03227

文献信息

• D-Glucosylated Derivatives of Isofagomine and Noeuromycin and Their Potential as Inhibitors of β-Glycoside Hydrolases
  作者：Peter J. Meloncelli、Tracey M. Gloster、Victoria A. Money、Chris A. Tarling、Gideon J. Davies、Stephen G. Withers、Robert V. Stick

  DOI：10.1071/ch07188

  日期：——

  While isofagomine and noeuromycin have previously been demonstrated to be effective inhibitors of a range of exo-acting glycosidases, they are usually only very weak inhibitors of endo-glycosidases. However, the disaccharide-like 3- and 4-O-β-d-glucopyranosylisofagomines have proven to be strong inhibitors of these endo-acting enzymes that utilize multiple sub-sites. In an attempt to emulate these successes, we have prepared 3- and 4-O-β-d-glucopyranosylnoeuromycin, the former by a selective glycosylation (at O2) of benzyl 4-C-cyano-4-deoxy-α-d-arabinoside (also leading to another synthesis of 3-O-β-d-glucopyranosylisofagomine), the latter by a non-selective glycosylation of benzyl 4-O-allyl-β-l-xyloside with subsequent introduction of the required nitrile group (also leading to another synthesis of 4-O-β-d-glucopyranosylisofagomine). 3-O-β-d-Glucopyranosylnoeuromycin was evaluated as an inhibitor of a family 26 lichenase from Clostridium thermocellum, and 4-O-β-d-glucopyranosylnoeuromycin as an inhibitor of both a family 5 endo-glucanase from Bacillus agaradhaerans and a family 10 endo-xylanase from Cellulomonas fimi. We also report X-ray structural investigations of 3- and 4-O-β-d-glucopyranosylnoeuromycin in complex with the family 26 and family 5 β-glycoside hydrolases, respectively. The two d-glucosylated noeuromycins were indeed able to harness the additional binding energy from the sub-sites of their endo-glycoside hydrolase targets, and were thus excellent inhibitors (in the nanomolar range), binding as expected in the –1 and –2 sub-sites of the enzymes.

  虽然异法哥明和新霉素以前已被证明是一系列外作用糖苷酶的有效抑制剂，但它们通常只是内作用糖苷酶的非常弱的抑制剂。然而，3-和 4-O-β-d-吡喃葡萄糖异抗淀粉样二糖已被证明是这些利用多个亚位点的内切酶的强抑制剂。为了效仿这些成功经验，我们制备了 3-和 4-O-β-d-吡喃葡萄糖基诺脲霉素，前者是通过对苄基 4-氰基-4-脱氧-α-d-阿拉伯糖苷进行选择性糖基化（在 O2 处）制备的（也导致了另一种 3-O-β-d-吡喃葡萄糖基异法哥明的合成）、后者是通过对苄基 4-O-烯丙基-β-l-木糖苷进行非选择性糖基化，然后引入所需的腈基（也可导致 4-O-β-d-glucopyranosylisofagomine 的另一种合成）。我们对 3-O-β-d-Glucopyranosylnoeuromycin 和 4-O-β-d-Glucopyranosylnoeuromycin 进行了评估，前者是热细胞梭菌（Clostridium thermocellum）26 族地衣酶的抑制剂，后者是琼脂芽孢杆菌（Bacillus agaradhaerans）5 族内切葡聚糖酶和纤维单胞菌（Cellulomonas fimi）10 族内切木聚糖酶的抑制剂。我们还报告了 3- 和 4-O-β-d-glucopyranosylnoeuromycin 分别与 26 族和 5 族 β-糖苷水解酶复合物的 X 射线结构研究。这两种 d-葡糖基化的新诺霉素确实能够利用其内糖苷水解酶目标亚位点的额外结合能，因此是极好的抑制剂（在纳摩尔范围内），如预期的那样与酶的-1 和-2 亚位点结合。
• The Synthesis of 3-O-(β-D-Glucopyranosyl)- and 3-O-(β-Laminaribiosyl)-isofagomines, Potent Inhibitors of a 1,3-β-D-Glucan endo-Hydrolase
  作者：James M. Macdonald、Maria Hrmova、Geoffrey B. Fincher、Robert V. Stick

  DOI：10.1071/ch03227

  日期：——

  mine with a D-glucosyl and a laminari-biosyl trichloroacetimidate has given, after removal of protecting groups, 3-O-(β-D-glucopyranosyl)- and 3-O-(β-laminaribiosyl)-isofagomines. Also included are similar glycosylations of a related tetrahydrooxazine. 3-O-(β-D-Glucopyranosyl)- and 3-O-(β-laminaribiosyl)-isofagomines acted as potent inhibitors of a barley 1,3-β-D-glucan endo-hydrolase, with ID50 values

  4,6-O-亚苄基-N-苄氧基羰基异法戈明与 D-葡糖基和海带-二糖基三氯乙酰亚胺酯的糖基化在去除保护基后得到 3-O-(β-D-吡喃葡萄糖基)-和 3-O -(β-海带核糖基)-异法戈明。还包括相关四氢恶嗪的类似糖基化。3-O-(β-D-Glucopyranosyl)- 和 3-O-(β-海带核糖基)-isofagomines 是大麦 1,3-β-D-葡聚糖内切水解酶的有效抑制剂，ID50 值为 7.8 和分别为 3.1 μM。