(2S,3R,4S)-2-(hydroxymethyl)piperidine-3,4-diol | 921199-28-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2S,3R,4S)-2-(hydroxymethyl)piperidine-3,4-diol
• 英文别名: (2S)-2beta-(Hydroxymethyl)piperidine-3beta,4beta-diol
• CAS: 921199-28-2
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: YZNNBIPIQWYLDM-HCWXCVPCSA-N

物化性质

• 沸点：
  315.4±42.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  10
• 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：
  72.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(adamantan-1-yl-methoxy)-1-bromo-pentane 、 (2S,3R,4S)-2-(hydroxymethyl)piperidine-3,4-diol 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (2S,3R,4S)-1-(5-(((3S,5S,7S)-adamantan-1-yl)methoxy)pentyl)-2-(hydroxymethyl)piperidine-3,4-diol
  参考文献：
  名称：

  部分脱氧脱氧野尻霉素衍生物作为葡糖神经酰胺合酶抑制剂的评估

  摘要：

  葡萄糖神经酰胺合酶 (GCS) 是一种已获批准的治疗戈谢病的药物靶点，被认为是对抗其他人类疾病（包括 2 型糖尿病）的有效靶点。临床药物N-丁基脱氧野尻霉素 (Zavesca) 被认为通过模拟其底物神经酰胺来抑制。在这项工作中，我们证明，与该模型中提出的相反，脱氧野尻霉素核心的 C2-羟基对于 GCS 抑制很重要。在这里，我们表明 C6-OH 似乎不那么重要，这可能为开发对其他糖加工酶（特别是作用于葡萄糖神经酰胺的水解酶）具有较低亲和力（与 Zavesca 相比）的 GCS 抑制剂制定指导方针。

  DOI：

  10.1021/ml200050s
• 作为产物：
  描述：

  (2S,3R,4S)-2-(hydroxymethyl)piperidine-3,4-diol hydrochloride 在 Ambersep 900 OH resin 作用下， 以 water-d1 为溶剂， 生成 (2S,3R,4S)-2-(hydroxymethyl)piperidine-3,4-diol
  参考文献：
  名称：

  4-羟基哌啶生物碱的对映体化学酶法合成

  摘要：

  报道了一种有效的化学酶合成法戈明对映体以及顺式和反式-4-羟基哌啶酸的对映体。该合成从商业 δ-戊内酰胺开始，在相应的磷酸乙烯酯的 Pd 催化甲氧基羰基化后，进行烯丙基氧化，得到外消旋 4-羟基四氢吡啶衍生物，总产率为 57%。使用来自南极念珠菌 (Novozym 435) 和洋葱伯克霍尔德菌 (脂肪酶 PS Amano IM) 的固定化脂肪酶，通过酶催化酯化来拆分该产物。后者分别提供 95% 和 94% ee 的相应 R 酯和 S 醇。然后通过立体选择性硼氢化/氧化将 S 醇转化为 L-fagomine 作为关键步骤，并通过立体选择性氢化转化为顺式-(2R,4S)-4-羟基哌啶酸。

  DOI：

  10.1002/ejoc.201000837

文献信息

• Stereoselective Aldol Additions Catalyzed by Dihydroxyacetone Phosphate-Dependent Aldolases in Emulsion Systems: Preparation and Structural Characterization of Linear and Cyclic Iminopolyols from Aminoaldehydes
  作者：Laia Espelt、Teodor Parella、Jordi Bujons、Conxita Solans、Jesús Joglar、Antonio Delgado、Pere Clapés

  DOI：10.1002/chem.200304966

  日期：2003.10.17

  hydroxyl group originating from the aldehyde. Characterization of the resulting iminocyclitols allowed the assessment of the diastereoselectivity of the enzymatic aldol reactions with respect to the N-protected aminoaldehyde. RAMA formed single diastereoisomers from N-Cbz-glycinal and from both enantiomers of N-Cbz-alaninal, while 14 % of the epimeric product was observed from N-Cbz-3-aminopropanal. Diastereoselectivity

  在许多情况下，磷酸二羟丙酮（DHAP）依赖性醛缩酶催化立体选择性醛缩醛加成的潜力受到受体醛在水/共溶剂混合物中的溶解度的限制。在这里，我们展示了乳液体系作为反应介质的效率，该反应介质是I类果糖-1,6-双磷酸醛缩醛醛糖酶（RAMA）和II类重组鼠李糖-1-磷酸醛糖醛缩醛醛糖酶从DHAP催化的DHAP之间的醛醇加成反应和N-苄氧基羰基（N-Cbz）氨基醛。相对于常规DMF /水混合物，乳液的使用将RAMA催化的羟醛转化率提高了三至十倍。无论反应介质如何，RhuA对N-Cbz氨基醛的反应性都比RAMA高。对于（S）-或（R）-Cbz-丙氨酸，RAMA表现出对R对映体的偏爱，而RhuA没有对映体歧视。将如此获得的线性N-Cbz氨基多元醇进行催化的分子内还原胺化，得到相应的亚氨基环醇。在所有检查的情况下，该反应都是非对映选择性的。面部选择性由源自醛的新形成的羟基的立体化学控制。所得亚氨基环醇的表征
• A Fluorescence Polarization Activity-Based Protein Profiling Assay in the Discovery of Potent, Selective Inhibitors for Human Nonlysosomal Glucosylceramidase
  作者：Daniël Lahav、Bing Liu、Richard J. B. H. N. van den Berg、Adrianus M. C. H. van den Nieuwendijk、Tom Wennekes、Amar T. Ghisaidoobe、Imogen Breen、Maria J. Ferraz、Chi-Lin Kuo、Liang Wu、Paul P. Geurink、Huib Ovaa、Gijsbert A. van der Marel、Mario van der Stelt、Rolf G. Boot、Gideon J. Davies、Johannes M. F. G. Aerts、Herman S. Overkleeft

  DOI：10.1021/jacs.7b07352

  日期：2017.10.11

  assessed on GBA2 selectivity offset against the other glucosylceramide metabolizing enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA), and the cytosolic retaining β-glucosidase, GBA3. Our work, yielding potent and selective GBA2 inhibitors, also provides a roadmap for the development of high-throughput assays for identifying retaining glycosidase inhibitors by FluoPol-ABPP

  人非溶酶体葡萄糖基神经酰胺酶（GBA2）是控制糖脂水平的几种酶之一，其活性与几种人类疾病状态相关。迫切需要设计或发现选择性的GBA2抑制剂作为化学工具和潜在的治疗剂。在这里，我们描述了基于荧光偏振活性的蛋白质谱分析（FluoPol-ABPP）测定法的发展，该测定法可从350多种亚氨基糖文库中快速鉴定GBA2抑制剂。基于FluoPol-ABPP筛选的线索生成聚焦库，并针对与其他葡糖神经酰胺代谢酶，葡糖神经酰胺合酶（GCS），溶酶体葡糖神经酰胺酶（GBA）和胞质保留β-葡糖苷酶GBA3的GBA2选择性偏移进行评估。我们的工作产生了有效的和选择性的GBA2抑制剂，
• Fructose-6-phosphate Aldolase in Organic Synthesis:  Preparation of <scp>d</scp>-Fagomine, <i>N</i>-Alkylated Derivatives, and Preliminary Biological Assays
  作者：José A. Castillo、Jordi Calveras、Josefina Casas、Montserrat Mitjans、M. Pilar Vinardell、Teodor Parella、Tomoyuki Inoue、Georg A. Sprenger、Jesús Joglar、Pere Clapés

  DOI：10.1021/ol0625482

  日期：2006.12.1

  straightforward two-step chemo-enzymatic synthesis of D-fagomine and some of its N-alkylated derivatives in 51% isolated yield and 99% de. The key step is the FSA-catalyzed aldol addition of simple dihydroxyacetone (DHA) to N-Cbz-3-aminopropanal. The use of FSA greatly simplifies the enzymatic procedures that used dihydroxyacetonephosphate or DHA/esters. Some N-alkyl derivatives synthesized elicited antifungal

  [结构：见正文] D-果糖-6-磷酸醛缩酶（FSA）以51％的分离产率和99％的de介导了D-fagomine及其某些N-烷基化衍生物的新颖，简单的两步化学酶法合成。关键步骤是在N-Cbz-3-氨基丙醛中FSA催化的简单二羟丙酮（DHA）的羟醛加成。FSA的使用大大简化了使用磷酸二羟基丙酮磷酸酯或DHA /酯的酶促程序。合成的一些N-烷基衍生物引起了抗真菌和抗菌活性以及增强的抑制活性，以及​​对β-半乳糖苷酶和α-葡萄糖苷酶的选择性。
• Organocatalyzed synthesis of (−)-4-epi-fagomine and the corresponding pipecolic acids
  作者：Jasna Marjanovic、Zorana Ferjancic、Radomir N. Saicic

  DOI：10.1016/j.tet.2015.07.036

  日期：2015.9

  The enantioselective synthesis of 4-epi-fagomine was accomplished starting from dioxanone and Cbz-protected benyzlamine, in 4 steps, with 18% overall yield. The key feature of this synthetic approach is the tactical combination of reactions: organocatalyzed aldolization/reductive amination, which allows for a quick formation of heterocyclic rings with defined absolute configuration of all stereogenic centers. Two hydroxypipecolic acids and a reduced fagomine analogue were also synthesized. (C) 2015 Elsevier Ltd. All rights reserved.
• Docking and SAR studies of d- and l-isofagomine isomers as human β-glucocerebrosidase inhibitors
  作者：Atsushi Kato、Saori Miyauchi、Noriko Kato、Robert J. Nash、Yuichi Yoshimura、Izumi Nakagome、Shuichi Hirono、Hiroki Takahata、Isao Adachi

  DOI：10.1016/j.bmc.2011.04.011

  日期：2011.6

  We report the structure-activity relationship of a series of D-, and L-isofagomine and fagomine isomers as glycosidase inhibitors. Our study revealed that a positive charge at the anomeric position of D-isofagomines enhanced the potency toward beta-glycosidases, while the epimerization at the C3 OH group drastically reduced their inhibitory potency by over three orders of magnitude. Furthermore, D-3,4-di-epi-isofagomine abolished their inhibition activities against all enzymes. L-Isofagomine was also a fairly potent inhibitor of human beta-glucocerebrosidase, with an IC50 value of 8.7 mu M. A molecular docking study revealed that the positions and orientations of the piperidine ring of D-3-epi-isofagomine in the binding site was similar to that of D-isofagomine, while D-3-epi-isofagomine missed the hydrogen bond interactions between Asp127 and the 3-OH group and between Trp179 and the 3-OH group. Furthermore, the top 10 docking models ranked by IFDscore suggested that D-3,4-di-epi-isofagomine can not bind to beta-glucocerebrosidase at a stable interaction mode. These results provide an insight into the structural requirements of isofagomine isomers for developing a new type of pharmacological chaperone for Gaucher disease. (C) 2011 Elsevier Ltd. All rights reserved.