(2R,3R,4R,5R)-2-(hydroxymethyl)-5-ethylpyrrolidine-3,4-diol | 1000855-15-1

• 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: (2R,3R,4R,5R)-2-(hydroxymethyl)-5-ethylpyrrolidine-3,4-diol
• 英文别名: (2r,3r,4r,5r)-2-Ethyl-5-(hydroxymethyl)pyrrolidine-3,4-diol
• CAS: 1000855-15-1
• 化学式: C₇H₁₅NO₃
• 分子量: 161.201
• InChiKey: TXUYISCBMIUUDE-DBRKOABJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  11
• 可旋转键数：
  2
• 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

• 作为产物：
  描述：

  (4S,5R,6R)-6-azido-4,5,7-trihydroxyheptan-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 (2R,3R,4R,5R)-2-(hydroxymethyl)-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。
• GLYCOSIDASE INHIBITORS AND USES THEREOF
  申请人：Alectos Therapeutics Inc.

  公开号：US20150274656A1

  公开（公告）日：2015-10-01

  The invention provides compounds for inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

  本发明提供了用于抑制糖苷酶的化合物，这些化合物的前药，以及包括这些化合物或其前药的制药组合物。本发明还提供了治疗与O-GlcNA酶的缺乏或过度表达、O-GlcNAc的积累或缺乏相关的疾病和障碍的方法。
• Selective Glycosidase Inhibitors and Uses Thereof
  申请人：Vocadlo David Jaro

  公开号：US20110301217A1

  公开（公告）日：2011-12-08

  The application relates to an immoalditol compound for selectively inhibiting glycosidases, a prodrug thereof and a pharmaceutical composition comprising the compound or the prodrug The application also relates to the use of the immoalditol compound for treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc Such diseases and disorders include neurodegenerative diseases, tauopathy, cancers, and cardiac disorders
• <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.