1-n-butyl-L-aravinoiminofuranose | 1186214-09-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-n-butyl-L-aravinoiminofuranose
• 英文别名: α-1-C-butyl-1,4-dideoxy-1,4-imino-L-arabinitol；α-1-C-butyl-LAB；(2S,3S,4S,5S)-2-(hydroxymethyl)pyrrolidine-5-butyl-3,4-diol；(2S,3S,4S,5S)-2-butyl-5-(hydroxymethyl)pyrrolidine-3,4-diol
• CAS: 1186214-09-4
• 化学式: C₉H₁₉NO₃
• 分子量: 189.255
• InChiKey: ZBUKLPRLOKVWJG-JBDRJPRFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  13
• 可旋转键数：
  4
• 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-n-butyl-L-aravinoiminofuranose 、 正丁醛 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以46%的产率得到(2S,3S,4S,5S)-1,2-dibutyl-5-(hydroxymethyl)pyrrolidine-3,4-diol
  参考文献：
  名称：

  α-1-C-Butyl-1,4-dideoxy-1,4-imino-l-arabinitol as a Second-Generation Iminosugar-Based Oral α-Glucosidase Inhibitor for Improving Postprandial Hyperglycemia

  摘要：

  We report on the synthesis and the biological evaluation of a series of alpha-1-C-alkylated 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. alpha-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 mu M, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of alpha-1-C-butyl-LAB and miglitol are clearly different. Furthermore, a-l-C-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. alpha-1-C-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia.

  DOI：

  10.1021/jm301304e
• 作为产物：
  描述：

  (5R,7aR)-5-(hydroxymethyl)-5,7a-dihydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one 在 咪唑 、 bis(1,5-cyclooctadiene)nickel (0) 、 potassium peroxymonosulfate 、 (R,R)-2,6-双(4-异丙基-2-恶唑啉-2-基)吡啶 、 乙二胺四乙酸 、 三氟乙酸甲酯 、 水 、 碘 、 碳酸氢钠 、 三苯基膦 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 、 乙腈 为溶剂， 生成 1-n-butyl-L-aravinoiminofuranose
  参考文献：
  名称：

  The synthesis and biological evaluation of 1-C-alkyl-l-arabinoiminofuranoses, a novel class of α-glucosidase inhibitors

  摘要：

  The asymmetric synthesis of 1-C-alkyl-L-arabinoiminofuranoses 1 was achieved by asymmetric allylic alkylation (AAA), ring closing metathesis (RCM), and Negishi cross coupling as key reactions. Some of the prepared compounds showed potent inhibitory activities towards intestinal maltase, with IC50 values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity (IC50 = 0.032 mu M) towards intestinal sucrase of 1c was quite strong compared to the above commercial drugs. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.112

文献信息

• Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties
  作者：Jordi Calveras、Meritxell Egido-Gabás、Livia Gómez、Josefina Casas、Teodor Parella、Jesús Joglar、Jordi Bujons、Pere Clapés

  DOI：10.1002/chem.200900838

  日期：2009.7.27

  The polyhydroxylated pyrrolidines generated were tested as inhibitors against seven glycosidases. Among them, good inhibitors of α‐L‐fucosidase (IC50=1–20 μM), moderate of α‐L‐rhamnosidase (IC50=7–150 μM), and weak of α‐D‐mannosidase (IC50=80–400 μM) were identified. The apparent inhibition constant values (Ki) were calculated for the most relevant inhibitors and computational docking studies were

  据报道，通过DHAP醛缩酶的催化，醛醇将磷酸二羟基丙酮磷酸酯（DHAP）加成到C-α-取代的N -Cbz-2-氨基醛衍生物上而生成的吡咯烷型亚氨基糖的化学酶法合成。来自大肠杆菌的L-藻糖-1-磷酸醛缩酶（FucA）和L-鼠李糖-1磷酸醛缩酶（RhuA）用作生物催化剂以在亚氨基糖上产生构型多样性。FucA催化剂可很好地耐受C-α处的烷基线性取代（即40-70％转化为醛醇加合物），而除二甲基和苄基取代（20％）外，未观察到具有C-α-烷基支链取代的产物。 。RhuA是用途最广泛的生物催化剂：C-α-烷基直链基团转化为羟醛加成物的转化率最高（60-99％），而C-α-烷基支链基团的转化率中等至良好（50-80％），二甲基和苄基取代基（20％）除外。FucA是最具立体选择性的生物催化剂（90％至100％的抗（3 R，4 R）加合物）。RhuA对（S）-N具有高度立体选择性-Cbz -2-氨基醛（90-100％顺式（即，3
• The synthesis and biological evaluation of 1-C-alkyl-l-arabinoiminofuranoses, a novel class of α-glucosidase inhibitors
  作者：Yoshihiro Natori、Tatsushi Imahori、Keiichi Murakami、Yuichi Yoshimura、Shinpei Nakagawa、Atsushi Kato、Isao Adachi、Hiroki Takahata

  DOI：10.1016/j.bmcl.2010.11.112

  日期：2011.1

  The asymmetric synthesis of 1-C-alkyl-L-arabinoiminofuranoses 1 was achieved by asymmetric allylic alkylation (AAA), ring closing metathesis (RCM), and Negishi cross coupling as key reactions. Some of the prepared compounds showed potent inhibitory activities towards intestinal maltase, with IC50 values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity (IC50 = 0.032 mu M) towards intestinal sucrase of 1c was quite strong compared to the above commercial drugs. (C) 2010 Elsevier Ltd. All rights reserved.
• TREATMENT OF LYSOSOMAL STORAGE DISORDERS AND OTHER PROTEOSTATIC DISEASES
  申请人：De Moor Olivier

  公开号：US20110237538A1

  公开（公告）日：2011-09-29

  Described are various compounds, in particular iminosugars, and methods for the treatment of proteostatic diseases, in particular lysosomal storage disorders. The compound may be a pharmacoperone of an enzyme selected from: (a) Acid alpha-glucosidase; (b) Acid beta-glucosidase; (c) glucocerebrosidase; (d) alpha-Galactosidase A; (e) Acid beta-galactosidase; (f) beta-Hexosaminidase A; (g) beta-Hexosaminidase B; (h) Acid sphingomyelinase; (i) Galactocerebrosidase; (j) Acid ceramidase; (k) Arylsulfatase A; (l) alpha-L-Iduronidase; (m) Iduronate-2-sulfatase; (n) Heparan N-sulfatase; (o) alpha-N-Acetylglucosaminidase; (p) Acetyl-CoA: alpha-glucosaminide N-acetyltransferase; (q) N-Acetylglucosamine-6-sulfate sulfatase; (r) N-Acetylgalactosamine-6-sulfate sulfatase; (s) Acid beta-galactosidase; (t) Arylsulfatase B; (u) beta-Glucuronidase; (v) Acid alpha-mannosidase; (w) Acid beta-mannosidase; (x) Acid alpha-L-fucosidase; (y) Sialidase; and (z) alpha-N-acetylgalactosaminidase.
• [EN] AGENT FOR AMELIORATING POSTPRANDIAL HYPERGLYCEMIA, AND PYRROLIDINE IMINOSUGAR OR SALT THEREOF<br/>[FR] AGENT PERMETTANT D'AMÉLIORER L'HYPERGLYCÉMIE POST-PRANDIALE ET IMINOSUCRE DE PYRROLIDINE OU SEL DE CELUI-CI
  申请人：NAT UNIV CORP UNIV TOYAMA

  公开号：WO2011058975A1

  公开（公告）日：2011-05-19

  　下記一般式［１］で表されるピロリジン型イミノ糖またはその塩を含有する食後過血糖改善剤。［式中、Ｒ１は、アリール基、ヒドロキシ基、および、保護されたヒドロキシ基からなる群から選択される基で置換されていてもよいアルキル基を示し；Ｒ２は、水素原子、アルキル基またはイミノ保護基を示し；Ｒ３、Ｒ４およびＲ５はそれぞれ、同一または異なって、水素原子またはヒドロキシ保護基を示す。］
• α-1-<i>C</i>-Butyl-1,4-dideoxy-1,4-imino-<scp>l</scp>-arabinitol as a Second-Generation Iminosugar-Based Oral α-Glucosidase Inhibitor for Improving Postprandial Hyperglycemia
  作者：Atsushi Kato、Erina Hayashi、Saori Miyauchi、Isao Adachi、Tatsushi Imahori、Yoshihiro Natori、Yuichi Yoshimura、Robert J. Nash、Hideyuki Shimaoka、Izumi Nakagome、Jun Koseki、Shuichi Hirono、Hiroki Takahata

  DOI：10.1021/jm301304e

  日期：2012.12.13

  We report on the synthesis and the biological evaluation of a series of alpha-1-C-alkylated 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. alpha-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 mu M, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of alpha-1-C-butyl-LAB and miglitol are clearly different. Furthermore, a-l-C-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. alpha-1-C-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia.