(2S,3S,4S,5S)-2-(hydroxymethyl)pyrrolidine-5-ethyl-3,4-diol | 1186213-95-5

• 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: (2S,3S,4S,5S)-2-(hydroxymethyl)pyrrolidine-5-ethyl-3,4-diol
• 英文别名: (2S,3S,4S,5S)-2-ethyl-5-(hydroxymethyl)pyrrolidine-3,4-diol
• CAS: 1186213-95-5
• 化学式: C₇H₁₅NO₃
• 分子量: 161.201
• InChiKey: TXUYISCBMIUUDE-AXMZGBSTSA-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：

  benzyl ((3S,4S,5R)-4,5,7-trihydroxy-6-oxoheptan-3-yl)carbamate 在 10% palladium on carbon 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 以63%的产率得到(2S,3S,4S,5S)-2-(hydroxymethyl)pyrrolidine-5-ethyl-3,4-diol
  参考文献：
  名称：

  磷酸二羟丙酮磷酸醛缩酶催化合成结构多样的多羟基吡咯烷衍生物及其糖苷酶抑制性能的评价

  摘要：

  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

  DOI：

  10.1002/chem.200900838

文献信息

• Highly efficient aldol additions of DHA and DHAP to N-Cbz-amino aldehydes catalyzed by l-rhamnulose-1-phosphate and l-fuculose-1-phosphate aldolases in aqueous borate buffer
  作者：Xavier Garrabou、Jordi Calveras、Jesús Joglar、Teodor Parella、Jordi Bujons、Pere Clapés

  DOI：10.1039/c1ob06263h

  日期：——

  Aldol addition reactions of dihydroxyacetone (DHA) to N-Cbz-amino aldehydes catalyzed by L-rhamnulose-1-phosphate aldolase (RhuA) in the presence of borate buffer are reported. High yields of aldol adduct (e.g. 70–90%) were achieved with excellent (>98 : 2 syn/anti) stereoselectivity for most S or R configured acceptors, which compares favorably to the reactions performed with DHAP. The stereochemical outcome was different and depended on the N-Cbz-amino aldehyde enantiomer: the S acceptors gave the syn (3R,4S) aldol adduct whereas the R ones gave the anti (3R,4R) diastereomer. Moreover, the tactical use of Cbz protecting group allows simple and efficient elimination of borate and excess of DHA by reverse phase column chromatography or even by simple extraction. This, in addition to the use of unphosphorylated donor nucleophile, makes a useful and expedient methodology for the synthesis of structurally diverse iminocyclitols. The performance of aldol additions of dihydroxyacetone phosphate (DHAP) to N-Cbz-amino aldehydes using RhuA and L-fuculose-1-phosphate aldolase (FucA) catalyst in borate buffer was also evaluated. For FucA catalysts, including FucA F131A, the initial velocity of the aldol addition reactions using DHAP were between 2 and 10 times faster and the yields between 1.5 and 4 times higher than those in triethanolamine buffer. In this case, the retroaldol velocities measured for some aldol adducts were lower than those without borate buffer indicating some trapping effect that could explain the improvement of yields.

  报告了二羟基丙酮（DHA）与N-Cbz-氨基醛的 aldol 加成反应，该反应是在硼酸盐缓冲液存在下，由 L-鼠李糖-1-磷酸 aldol 酶（RhuA）催化进行的。大部分 S或 R 配置的受体都可以以高产率（例如 70–90%）获得 aldol 加合物，并具有优异的立体选择性（>98 : 2 syn/anti），这与使用 DHAP 进行的反应相比表现良好。立体化学结果不同，依赖于 N-Cbz-氨基醛的对映异构体：S 受体产生 syn（3R,4S）aldol 加合物，而 R 受体则产生 anti（3R,4R）联体异构体。此外，策略性地使用 Cbz 保护基团使得通过反相色谱或简单提取可以简单高效地去除硼酸盐和多余的 DHA。这一点，加上使用未磷酸化的供体亲核试剂，使得合成结构多样性免疫环醇的方法更为实用和高效。同时，评估了使用 RhuA 和 L-岩藻糖-1-磷酸 aldol 酶（FucA）催化剂在硼酸盐缓冲液中对 N-Cbz-氨基醛进行二羟基丙酮磷酸盐（DHAP）进行的 aldol 加成反应的表现。对于 FucA 催化剂（包括 FucA F131A），使用 DHAP 的 aldol 加成反应的初始速率是三乙醇胺缓冲液中反应的 2 到 10 倍，产率高出 1.5 到 4 倍。在这种情况下，测得某些 aldol 加合物的逆 aldol 速率低于不含硼酸盐缓冲液的情况，这表明存在某种捕获效应，可以解释产率的提高。
• 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.
• 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.
• COMBINATIONS COMPRISING A VEGF RECEPTOR INHIBITOR AND A PENETRATION ENHANCER
  申请人：Novartis AG

  公开号：EP1945217B1

  公开（公告）日：2012-05-02
• Bicyclic Amides as Kinase Inhibitors
  申请人：Bold Guido

  公开号：US20080287427A1

  公开（公告）日：2008-11-20

  The invention relates to compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising en a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in particular tumour diseases.