(+)-trans-4-hydroxypipecolic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (+)-trans-4-hydroxypipecolic acid
• 英文别名: (2R,4R)-4-hydroxypiperidine-2-carboxylic acid；(2R,4R)-4-hydroxypiperidin-1-ium-2-carboxylate
• 化学式: C₆H₁₁NO₃
• 分子量: 145.158
• InChiKey: KRHNXNZBLHHEIU-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-trans-4-hydroxypipecolic acid 生成 六氢吡啶-alpha-羧酸
  参考文献：
  名称：

  SWAIN, LEE A.;ROMEO, JOHN T., PHYTOCHEMISTRY, 27,(1988) N 2, 397-399

  摘要：

  DOI：
• 作为产物：
  描述：

  Methyl 2-[but-3-enyl(ethoxycarbonyl)amino]-2-hydroxyacetate 在 盐酸 作用下， 反应 90.0h， 生成 (+)-trans-4-hydroxypipecolic acid
  参考文献：
  名称：

  Formic acid-induced π-cyclization of glycine cation equivalents to substituted pipecolic acid derivatives

  摘要：

  Formic acid-mediated cyclization reactions of N-(3-alkenyl)-N-(methoxycarbonyl)-acetoxyglycine esters are described. The major reaction products are 4-formyloxypipecolic acid derivatives, formed with low stereoselectivity at C-4. The several subtle features of the cyclization process are satisfactorily explained by a mechanism involving (1) a rapid cationic aza-Cope rearrangement of the incipient iminium ion and (2) participation of the ester moiety through formation of a relatively stable bicyclic dioxycarbenium cation as pivotal intermediate.

  DOI：

  10.1016/s0040-4020(01)86444-9

文献信息

• Improved Total Synthesis of Tubulysins and Design, Synthesis, and Biological Evaluation of New Tubulysins with Highly Potent Cytotoxicities against Cancer Cells as Potential Payloads for Antibody–Drug Conjugates
  作者：K. C. Nicolaou、Rohan D. Erande、Jun Yin、Dionisios Vourloumis、Monette Aujay、Joseph Sandoval、Stefan Munneke、Julia Gavrilyuk

  DOI：10.1021/jacs.7b12692

  日期：2018.3.14

  streamlined total syntheses of natural tubulysins such as V (Tb45) and U (Tb46) and pretubulysin D (PTb-D43), and their application to the synthesis of designed tubulysin analogues (Tb44, PTb-D42, PTb-D47-PTb-D49, and Tb50-Tb120), are described. Cytotoxicity evaluation of the synthesized compounds against certain cancer cell lines revealed a number of novel analogues with exceptional potencies [e.g., Tb111:

  V (Tb45) 和 U (Tb46) 和 pretubulysin D (PTb-D43) 等天然微管溶素的改进、简化的全合成，以及它们在合成设计的微管溶素类似物（Tb44、PTb-D42、PTb-D47-PTb）中的应用-D49 和 Tb50-Tb120)，进行了描述。合成化合物对某些癌细胞系的细胞毒性评估揭示了许多具有特殊效力的新型类似物[例如，Tb111：IC50 = 40 pM 对 MES SA（子宫肉瘤）细胞系；针对 HEK 293T（人胚胎肾癌）细胞系的 IC50 = 6 pM；和 IC50 = 1.54 nM，对 MES SA DX（具有明显多重耐药性的 MES SA）细胞系]。这些研究产生了一组有价值的构效关系，为进一步的分子设计、合成和生物学评价研究提供指导。
• A Concise and Diastereoselective Synthesis of Piperidine and Indolizidine Alkaloids via Aza-Prins Cyclization
  作者：Basi Reddy、Dudhmal Chaya、Jhillu Yadav、René Grée

  DOI：10.1055/s-0031-1289648

  日期：2012.1

  The synthesis of 2-substituted and 2,4-disubstituted piperidine alkaloids such as (±)-coniine, (±)-hydroxypipecolic acid, (±)-pipecolic acid, (±)-coniceine, and (±)-4-hydroxy-2-hydroxy­methyl piperidine have been accomplished in a highly diastereo­selective manner by employing aza-Prins cyclization as a key step to construct the piperidine core of these alkaloids. aza-Prins cyclization - diastereoselective

  2-取代和2,4-二取代哌啶生物碱的合成，例如（±）-con氨酸，（±）-羟基哌酸，（±）-哌酸，（±）-癸酸和（±）-4-羟基通过采用氮杂-Prins环化作为构建这些生物碱的哌啶核心的关键步骤，以高度非对映选择性的方式完成了-2-羟甲基哌啶。 aza-Prins环化-非对映选择性-哌啶-生物碱-天然产物
• Asymmetric Synthesis of the Four Stereoisomers of 4-Hydroxypipecolic Acid
  作者：Franklin A. Davis、Tianan Fang、Bin Chao、David M. Burns

  DOI：10.1055/s-2000-8710

  日期：——

  The asymmetric synthesis of all four stereoisomers of 4-hydroxypipecolic acid (1) from the polyfunctionalized chiral building blocks δ-amino β-keto esters (S S, R)-(+)-5 or (R s, S)-(-)-5 is described. Key steps in the synthesis are the stereoselective reductions of b-phenylpiperidine-2,4-dione (6) and N-sulfinyl δ-amino β-keto esters 5 to cis-4-hydroxy 2-piperidinone 7 and syn-δ-amino β-hydroxy ester 9, respectively. The only protecting/deprotecting group chemistry required is related to the oxidation step.

  描述了从多功能手性构建块 δ-氨基 β-酮酯 (S S, R)-(+)-5 或 (R s, S)-(-)-5 不对称合成4-羟基皮克酸 (1) 的四种立体异构体。合成的关键步骤是对 β-苯基哌啶-2,4-二酮 (6) 和 N-亚砜基 δ-氨基 β-酮酯 5 的立体选择性还原，分别得到顺式的4-羟基-2-哌啶酮 7 和 syn-δ-氨基 β-羟基酯 9。所需的唯一保护/去保护基团化学与氧化步骤有关。
• [EN] AN ENANTIOSELECTIVE PROCESS FOR THE SYNTHESIS OF (2S,4R)-4-HYDROXYPIPECOLIC ACID<br/>[FR] PROCÉDÉ ÉNANTIOSÉLECTIF DE SYNTHÈSE D'ACIDE (2S,4R)-4-HYDROXYPIPÉCOLIQUE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2016120890A1

  公开（公告）日：2016-08-04

  The present invention relates to an improved process for synthesis of 4-hydroxy pipecolic acid. The present invention relates to an improved enantioselective process for the synthesis of (2S,4R)-4-hydroxypipecolic acid via Co(III) (salen)-catalyzed two stereocentered Hydrolytic Kinetic Resolution (HKR) of racemic 1,3-azido epoxide with good yields and high optical purity without any protecting groups. 10 31

  本发明涉及一种改进的合成4-羟基吡哆酸的方法。本发明涉及一种改进的不对称选择性过程，用于通过Co(III) (salen)催化的两个立体中心水解动力学分辨（HKR）合成(2S,4R)-4-羟基吡哆酸，具有良好的产率和高光学纯度，且无需任何保护基团。
• 2-Keto-3-Deoxy-<scp>l</scp>-Rhamnonate Aldolase (YfaU) as Catalyst in Aldol Additions of Pyruvate to Amino Aldehyde Derivatives
  作者：Karel Hernández、Ariadna Gómez、Jesús Joglar、Jordi Bujons、Teodor Parella、Pere Clapés

  DOI：10.1002/adsc.201700360

  日期：2017.6.19

  (R)‐N‐Cbz‐amino aldehydes. Addition reactions to achiral amino aldehydes rendered racemic aldol adducts. Molecular models of the pre‐reaction ternary complexes YfaU‐pyruvate enolate‐acceptor aldehyde were constructed to explain the observed stereochemical outcome of the reactions. Catalytic reductive amination of the aldol adducts yielded 4‐hydroxy‐2‐pipecolic acid, and unprecedented C‐5 substituted 4‐hydroxyproline

  4-羟基-2-酮酸衍生物是合成氨基酸，羟基羧酸和手性醛的通用构建基块。丙酮酸醛缩酶是直接获得这类酮酸化合物的特权催化剂。在这项工作中，评估了大肠杆菌K-12的II类丙酮酸醛缩酶，2-酮基3-脱氧-1-鼠李糖醛酸醛缩酶（YfaU）的脯氨酸，哌啶酸和吡咯并立定的氨基酸衍生物的合成。 3-羧酸。丙酮酸向N-保护的氨基醛中醛缩醛的加成是关键的酶促醛缩醛加成步骤，随后是催化的分子内还原胺化。对应的N‐Cbz‐氨基-4-羟基-2-酮酸（Cbz =苄氧羰基）前体的分离产率为51–95％，对映选择性比率为26:74至95：5，具有手性α-取代的N -Cbz-氨基醛。（S）-N -Cbz-氨基乙醛在新形成的立体中心生成具有（R）-构型的羟醛加合物，而（R）-N则相反-Cbz-氨基醛。非手性氨基醛的加成反应得到外消旋的醇醛加合物。建立了反应前三元复合物YfaU-丙酮酸烯醇盐-受体醛的分子模型，以解释观察到的反