2,5-dideoxy-2,5-imino-L-mannitol | 219562-44-4

• 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: 2,5-dideoxy-2,5-imino-L-mannitol
• 英文别名: L-DMDP；(2S,3S,4S,5S)-2,5-bis(hydroxymethyl)pyrrolidine-3,4-diol
• CAS: 219562-44-4
• 化学式: C₆H₁₃NO₄
• 分子量: 163.174
• InChiKey: PFYHYHZGDNWFIF-BXKVDMCESA-N

物化性质

• 熔点：
  116-117 °C(Solv: methanol (67-56-1))
• 沸点：
  395.9±37.0 °C(Predicted)
• 密度：
  1.408±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 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：
  93
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,5-dideoxy-2,5-imino-L-mannitol 、 1-硫代异氰酸辛酯 在 三乙胺 作用下， 以 吡啶 为溶剂， 反应 21.0h， 以85%的产率得到(2S,3S,4S,5S)-3,4-dihydroxy-2,5-bis(hydroxymethyl)pyrrolidine-1-carbothioic acid octylamide
  参考文献：
  名称：

  设计选择性α-1-鼠李糖苷酶抑制剂的策略：1-DMDP环状异硫脲的合成和生物学评估。

  摘要：

  该研究表明，将1-DMDP硫脲脲环化为双环1-DMDP异硫脲可改善α-1-鼠李糖苷酶的抑制作用，并通过增加烷基链的长度进一步增强了抑制作用。向氮中添加长烷基链（例如癸基或十二烷基）导致产生强力的α-1-鼠李糖苷酶抑制剂。它也引起了针对β-葡萄糖苷酶和β-半乳糖苷酶的广泛抑制谱。相反，相应的N-苄基-1-DMDP环状异硫脲显示出对α-1-鼠李糖苷酶的选择性抑制。发现3'，4'-二氯苄基-1-DMDP环状异硫脲（3r）对α-1-鼠李糖苷酶显示出最有效和选择性的抑制作用，IC50值为0.22μM，比阳性对照好46倍5 -epi-deoxyrhamnojirimycin（5-epi-DRJ; IC50 =10μM）并占据了该酶的活性位点（Ki =0.11μM）。偶氮-1-DMDP的双环异硫脲不抑制α-1-鼠李糖苷酶。这些新的鼠李糖模拟物可能会影响与鼠李糖生物化学相关的其他酶，包括与结核病进展有关的酶。

  DOI：

  10.1016/j.bmc.2016.10.015
• 作为产物：
  描述：

  Methanesulfonic acid (1R,2R,3R,4R)-4-methanesulfonyloxy-2,3,5-tris-methoxymethoxy-1-methoxymethoxymethyl-pentyl ester 在 palladium dihydroxide 氢气 、 三氟乙酸 作用下， 以 溶剂黄146 为溶剂， 25.0~120.0 ℃ 、101.33 kPa 条件下， 反应 18.0h， 生成 2,5-dideoxy-2,5-imino-L-mannitol
  参考文献：
  名称：

  Enantioselective Approach to Polyhydroxylated Compounds Using Chiral Sulfoxides:  Synthesis of Enantiomerically Pure myo-Inositol and Pyrrolidine Derivatives

  摘要：

  A short enantioselective synthesis of the biologically important myo-inositol derivative I and the pyrrolidine derivative II is described. The molecule 3, a diketo disulfoxide readily made from tartaric acid, is the key intermediate. The sulfinyl group controlled completely the very high stereoselection observed.

  DOI：

  10.1021/jo9811569

文献信息

• Borate as a Phosphate Ester Mimic in Aldolase-Catalyzed Reactions: Practical Synthesis ofL-Fructose andL-Iminocyclitols
  作者：Masakazu Sugiyama、Zhangyong Hong、Lisa J. Whalen、William A. Greenberg、Chi-Huey Wong

  DOI：10.1002/adsc.200600356

  日期：2006.12

  Dihydroxyacetone phosphate (DHAP)-dependent aldolases have been widely used for the organic synthesis of unnatural sugars or derivatives. The practicality of using DHAP-dependent aldolases is limited by their strict substrate specificity and the high cost and instability of DHAP. Here we report that the DHAP-dependent aldolase L-rhamnulose 1-phosphate aldolase (RhaD) accepts dihydroxyacetone (DHA)

  磷酸二羟基丙酮（DHAP）依赖性醛缩酶已广泛用于非天然糖或衍生物的有机合成。使用依赖DHAP的醛缩酶的实用性受到其严格的底物特异性以及DHAP的高成本和不稳定性的限制。在这里我们报告依赖DHAP的醛缩酶L-鼠李糖1-磷酸醛缩酶（RhaD）在硼酸盐缓冲液的存在下接受二羟基丙酮（DHA）作为供体底物，大概是通过原位可逆的形成DHA硼酸酯。该反应似乎是不可逆的，热力学上将产物捕获为硼酸盐配合物。我们已经将该发现用于开发非热量甜味剂L-果糖的实用一步合成。在RhaD存在下，由消旋甘油醛和DHA合成L-果糖，硼酸盐的克收率为92％。我们还分两步合成了一系列L-亚氨基环糖醇，它们是潜在的糖苷酶抑制剂。
• l-DMDP, l-homoDMDP and their C-3 fluorinated derivatives: synthesis and glycosidase-inhibition
  作者：Yi-Xian Li、Mu-Hua Huang、Yukiko Yamashita、Atsushi Kato、Yue-Mei Jia、Wu-Bao Wang、George W. J. Fleet、Robert J. Nash、Chu-Yi Yu

  DOI：10.1039/c0ob01063d

  日期：——

  L-DMDP and L-homoDMDP, the enantiomers of naturally occurring DMDP and homoDMDP have been synthesized from D-xylose derived cyclic nitrone 9. Their 3-deoxy-3-fluorinated analogues were also obtained from polyhydroxylated fluorinated cyclic nitrone 10, which was prepared from fluorinated sugar 12 in seven steps. Bioactivities of these iminosugars against various glycosidases were evaluated. While L-DMDP and L-homoDMDP are potent inhibitors of α-glucosidases, a sharp decrease of inhibition was found when the C-3 hydroxyl group of these compounds was replaced by fluoride, which showed the great importance of the C-3 hydroxyl in their interaction with enzymes.

  L-DMDP和L-homoDMDP是天然存在的DMDP和homoDMDP的对映体，已通过从D-木糖衍生的环状亚硝酮9合成。它们的3-去氧-3-氟化类似物也通过从氟化糖12经过七步反应制备的多羟基氟化环状亚硝酮10获得。这些亚氨糖对多种糖苷酶的生物活性进行了评估。虽然L-DMDP和L-homoDMDP是α-葡萄糖苷酶的强抑制剂，但当这些化合物的C-3羟基被氟替代时，抑制作用明显下降，这显示了C-3羟基在与酶相互作用中的重要性。
• [EN] METHODS OF TREATING POMPE DISEASE<br/>[FR] MÉTHODES DE TRAITEMENT DE LA MALADIE DE POMPE
  申请人：ACADEMIA SINICA

  公开号：WO2021067324A1

  公开（公告）日：2021-04-08

  Disclosed herein are novel uses of ADMDP stereoisomers or their derivatives for the manufacture of a medicament for treating Pompe disease. Accordingly, the present disclosure provides a method of treating Pompe disease in a subject. The method includes the step of, administering to the subject a therapeutically effective amount of a compound of formula (I), or a salt, an ester or a solvate thereof, wherein R1 and R2 are independently H or alkyl optionally substituted by -NH2 or -OH, so as to ameliorate, alleviate mitigate and/or prevent symptoms associated with the Pompe disease. According to certain embodiments of the present disclosure, the compound of formula (I) may serve a stabilizer of α-glucosidase via preventing its denaturalization of deactivation.

  本公开揭示了ADMDP立体异构体或其衍生物的新用途，用于制造治疗庞贝病的药物。因此，本公开提供了一种治疗庞贝病的方法。该方法包括向受试者施用化合物(I)的治疗有效量，或其盐、酯或溶剂，其中R1和R2独立地为H或烷基，可以选择地被-NH2或-OH取代，以改善、减轻、缓解和/或预防与庞贝病相关的症状。根据本公开的某些实施例，化合物(I)可以作为α-葡萄糖苷酶的稳定剂，通过防止其变性或失活。
• Studies towards the synthesis of polyhydroxylated pyrrolidine alkaloids isolated from Broussonetia kazinoki (moraceae)
  作者：Marc E. Bouillon、Robert J. Nash、Stephen G. Pyne

  DOI：10.1016/j.tet.2022.133104

  日期：2022.12

  (−)-(6S)-12′-hydroxydodecylmoranoline are reported. These syntheses start from d-xylose employing the Petasis borono-Mannich reaction to stereoselectively introduce the amino group, followed by a chemo- and regioselective O-mesylation to deliver the fully functionalized pyrrolidine moiety after intramolecular SN2-cyclisation. The synthesis of the latter targeted compound involved a ring expansion process of

  L-AB1、L-DMDP 和新型化合物 (−)-phenethyl-L-AB1、(−)-10′-deoxobroussonetine C、(−)-10′-deoxobroussonetine E、(−)-报道了 1'-epi-10'-deoxobroussonetine E 和 (−)-(6S)-12'-hydroxydodecylmoranoline。这些合成从d -木糖开始，采用 Petasis 硼-曼尼希反应立体选择性地引入氨基，然后进行化学和区域选择性 O-甲磺酰化，在分子内 S N之后传递完全功能化的吡咯烷部分2-环化。后一种目标化合物的合成涉及脯氨醇部分在 Mitsunobu 反应条件下扩环成哌啶衍生物的过程。由于在合成的最后阶段形成了意想不到的四氢呋喃衍生物，因此尝试合成所需的 ent-broussonetine C 未成功。还介绍了四种新目标化合物对一组十种糖苷的糖苷酶抑制活性。
• Looking glass inhibitors: scalable syntheses of DNJ, DMDP, and (3R)-3-hydroxy-l-bulgecinine from d-glucuronolactone and of l-DNJ, l-DMDP, and (3S)-3-hydroxy-d-bulgecinine from l-glucuronolactone. DMDP inhibits β-glucosidases and β-galactosidases whereas l-DMDP is a potent and specific inhibitor of α-glucosidases
  作者：Daniel Best、Chen Wang、Alexander C. Weymouth-Wilson、Robert A. Clarkson、Francis X. Wilson、Robert J. Nash、Saori Miyauchi、Atsushi Kato、George W.J. Fleet

  DOI：10.1016/j.tetasy.2010.01.017

  日期：2010.3

  A convenient large-scale synthesis of 1-deoxynojirimyin (DNJ) from D-glucuronolactone involves introduction of azide at C-5 with retention of configuration to give 5-azido-5-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranose as a key intermediate in an overall yield of up to 72%; the same intermediate can be transformed into DMDP (2R,3R,4R,5R)-2,5-bis(hydroxymethyl)pyrrolidine-3,4-diol] and (3R)-3-hydroxy-L-bulgecinine [(2S,3R,4R,5R)-3,4-dihydroxy-5-hydroxymethyl-L-proline]. L-Glucuronolactone, a readily available L-sugar chiron, may similarly be used to access the enantiomers L-DNJ, L-DMDP, and (3S)-3-hydroxy-D-bulgecinine. A comparison of glycosidase inhibition by DMDP (an inhibitor of beta-glucosidases and beta-galactosidases) and L-DMDP (a potent and specific alpha-glucosidase inhibitor) with the corresponding enantiomeric hydroxybulgecinines is reported; DMDP and (3R)-3-hydroxy-L-bulgecinine show weak inhibition of glycogen phosphorylase. (C) 2010 Elsevier Ltd. All rights reserved.