(3R,4R,5R)-5-ethylpyrrolidine-3,4-diol | 606933-28-2

• 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: (3R,4R,5R)-5-ethylpyrrolidine-3,4-diol
• 英文别名: (2R,3R,4R)-2-ethylpyrrolidine-3,4-diol
• CAS: 606933-28-2
• 化学式: C₆H₁₃NO₂
• 分子量: 131.175
• InChiKey: DPKVFORGPDPGQG-HSUXUTPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  9
• 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：
  52.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R,4R,5R)-5-ethylpyrrolidine-3,4-diol 在 二氯乙酸 、 sodium methylate 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 18.0h， 生成 8-(methoxycarbonyl)octyl 5-deoxy-5-(1,4,5-trideoxy-1,4-imino-5-C-methyl-D-arabinitol-N-yl)-α-D-arabinofuranoside
  参考文献：
  名称：

  新型分枝杆菌阿拉伯呋喃糖基转移酶抑制剂亚氨基糖-寡聚阿拉伯呋喃糖苷杂合体的合成和生物学评价

  摘要：

  分枝杆菌细胞壁是开发新型抗结核药物的一个有前景的靶点。我们报告了亚氨基糖-寡聚阿拉伯呋喃糖苷杂合物的合成和初步生物学评价，这是一类新的分枝杆菌阿拉伯糖基转移酶抑制剂。这些杂合体是由各种手性多羟基吡咯烷（亚氨基糖）与小寡聚阿拉伯呋喃糖苷连接而成的。偶联反应是合适的低聚阿拉伯呋喃糖苷醛与未保护的胺对应物的还原胺化。对于一些以放射性[ 14 C]-DPA 作为糖基供体的杂合体，观察到良好的体外阿拉伯糖基转移酶抑制作用，更重要的是，它们的抑制活性受寡糖部分的长度调节。该结果表明，这些分枝杆菌酶的潜在抑制剂可以通过将它们与受体样寡聚阿拉伯呋喃糖苷连接来制备。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

  DOI：

  10.1002/ejoc.200300003
• 作为产物：
  描述：

  (4S,5R)-6-azido-4,5-dihydroxyhexan-3-one 在 palladium dihydroxide 氢气 、 二乙胺 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 20.0 ℃ 、2.76 MPa 条件下， 生成 (3R,4R,5R)-5-ethylpyrrolidine-3,4-diol
  参考文献：
  名称：

  d-Fructose-6-Phosphate Aldolase-Catalyzed One-Pot Synthesis of Iminocyclitols

  摘要：

  A one-pot chemoenzymatic method for the synthesis of a variety of new iminocyclitols from readily available, non-phosphorylated donor substrates has been developed. The method utilizes the recently discovered fructose-6-phosphate aldolase (FSA), which is functionally distinct from known aldolases in its tolerance of different donor substrates as well as acceptor substrates. Kinetic studies were performed with dihydroxyacetone (DHA), the presumed endogenous substrate for FSA, as well as hydroxy acetone (HA) and 1-hydroxy-2-butanone (HB) as donor substrates, in each case using glyceraidehyde-3-phosphate as acceptor substrate. Remarkably, FSA used the three donor substrates with equal efficiency, with k(cat)/K-M-values of 33, 75, and 20 M-1 s(-1), respectively. This level of donor substrate tolerance is unprecedented for an aldolase. Furthermore, DHA, HA, and HB were accepted as donors in FSA-catalyzed aldol reactions with a variety of azido- and Cbz-amino aldehyde acceptors. The broad substrate tolerance of FSA and the ability to circumvent the need for phosphorylated substrates allowed for one-pot synthesis of a number of known and novel iminocyclitols in good yields, and in a very concise fashion. New iminocyclitols were assayed as inhibitors against a panel of glycosidases. Compounds 15 and 16 were specific alpha-mannosidase inhibitors, and 24 and 26 were potent and selective inhibitors of beta-N-acetylglucosaminidases in the submicromolar range. Facile access to these compounds makes them attractive core structures for further inhibitor optimization.

  DOI：

  10.1021/ja073911i

文献信息

• Structure-Guided Engineering of <scp>D</scp> -Fructose-6-Phosphate Aldolase for Improved Acceptor Tolerance in Biocatalytic Aldol Additions
  作者：Anna Soler、Mariana L. Gutiérrez、Jordi Bujons、Teodor Parella、Cristina Minguillon、Jesús Joglar、Pere Clapés

  DOI：10.1002/adsc.201500073

  日期：2015.5.26

  structure‐guided redesign of D‐fructose‐6‐phosphate aldolase from Escherichia coli (FSA) was devised for improving the acceptor tolerance towards α‐substituted and conformationally constrained aldehydes. FSA A129S/R134X/A165G/S166G and L107Y/A129G/R134X/A165G/S166G variants, where X was R, V, P, or S, were the most suited biocatalysts for dihydroxyacetone, hydroxyacetone and glycolaldehyde additions to 20 α‐substituted

  为提高受体对α-取代的和构象受限的醛的耐受性，设计了来自大肠杆菌（FSA）的D-果糖-6-磷酸醛缩酶醛缩酶的结构指导的重新设计。FSA A129S / R134X / A165G / S166G和L107Y / A129G / R134X / A165G / S166G变体，其中X为R，V，P或S，是向20个α-取代的N加成二羟基丙酮，羟丙酮和乙醇醛的最合适生物催化剂。-Cbz-氨基醛（Cbz =苄氧羰基），包括吡咯烷和哌啶衍生物。对于全动态立体控制SI -SI面加入醛缩酶-结合的亲核试剂到的Ñ观察-CBZ-氨基醛羰基，家具相应d -苏式配置羟醛加合物> 95:5博士通过NMR评估的。还原胺化后，鉴定并表征了47种不同的亚氨基环醇。在一些实施例中，观察到相应醛的部分外消旋化，这似乎主要在醛醇加成反应期间产生。
• <scp>d</scp>-Fructose-6-Phosphate Aldolase-Catalyzed One-Pot Synthesis of Iminocyclitols
  作者：Masakazu Sugiyama、Zhangyong Hong、Pi-Hui Liang、Stephen M. Dean、Lisa J. Whalen、William A. Greenberg、Chi-Huey Wong

  DOI：10.1021/ja073911i

  日期：2007.11.28

  A one-pot chemoenzymatic method for the synthesis of a variety of new iminocyclitols from readily available, non-phosphorylated donor substrates has been developed. The method utilizes the recently discovered fructose-6-phosphate aldolase (FSA), which is functionally distinct from known aldolases in its tolerance of different donor substrates as well as acceptor substrates. Kinetic studies were performed with dihydroxyacetone (DHA), the presumed endogenous substrate for FSA, as well as hydroxy acetone (HA) and 1-hydroxy-2-butanone (HB) as donor substrates, in each case using glyceraidehyde-3-phosphate as acceptor substrate. Remarkably, FSA used the three donor substrates with equal efficiency, with k(cat)/K-M-values of 33, 75, and 20 M-1 s(-1), respectively. This level of donor substrate tolerance is unprecedented for an aldolase. Furthermore, DHA, HA, and HB were accepted as donors in FSA-catalyzed aldol reactions with a variety of azido- and Cbz-amino aldehyde acceptors. The broad substrate tolerance of FSA and the ability to circumvent the need for phosphorylated substrates allowed for one-pot synthesis of a number of known and novel iminocyclitols in good yields, and in a very concise fashion. New iminocyclitols were assayed as inhibitors against a panel of glycosidases. Compounds 15 and 16 were specific alpha-mannosidase inhibitors, and 24 and 26 were potent and selective inhibitors of beta-N-acetylglucosaminidases in the submicromolar range. Facile access to these compounds makes them attractive core structures for further inhibitor optimization.
• Synthesis and Biological Evaluation of Imino Sugar−Oligoarabinofuranoside Hybrids, a New Class of Mycobacterial Arabinofuranosyltransferase Inhibitors
  作者：Karine Marotte、Tahar Ayad、Yves Génisson、Gurdyal S. Besra、Michel Baltas、Jacques Prandi

  DOI：10.1002/ejoc.200300003

  日期：2003.7

  The mycobacterial cell wall is a promising target for the development of new antituberculosis drugs. We report the synthesis and preliminary biological evaluation of imino sugar−oligoarabinofuranoside hybrids, a new class of mycobacterial arabinosyltransferase inhibitors. These hybrids were built from various chiral polyhydroxylated pyrrolidines (imino sugars) linked to small oligoarabinofuranosides

  分枝杆菌细胞壁是开发新型抗结核药物的一个有前景的靶点。我们报告了亚氨基糖-寡聚阿拉伯呋喃糖苷杂合物的合成和初步生物学评价，这是一类新的分枝杆菌阿拉伯糖基转移酶抑制剂。这些杂合体是由各种手性多羟基吡咯烷（亚氨基糖）与小寡聚阿拉伯呋喃糖苷连接而成的。偶联反应是合适的低聚阿拉伯呋喃糖苷醛与未保护的胺对应物的还原胺化。对于一些以放射性[ 14 C]-DPA 作为糖基供体的杂合体，观察到良好的体外阿拉伯糖基转移酶抑制作用，更重要的是，它们的抑制活性受寡糖部分的长度调节。该结果表明，这些分枝杆菌酶的潜在抑制剂可以通过将它们与受体样寡聚阿拉伯呋喃糖苷连接来制备。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)