tert-butyl (R)-5-oxotetrahydrofuran-2-carboxylate | 176237-48-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: tert-butyl (R)-5-oxotetrahydrofuran-2-carboxylate
• 英文别名: Tert-butyl (2R)-5-oxooxolane-2-carboxylate
• CAS: 176237-48-2
• 化学式: C₉H₁₄O₄
• 分子量: 186.208
• InChiKey: YLXNLHFGLNCGEK-ZCFIWIBFSA-N

物化性质

• 沸点：
  289.5±33.0 °C(Predicted)
• 密度：
  1.139±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-5-oxotetrahydrofuran-2-carboxylate 在 磺酰氯 、 三氟乙酸 作用下， 以 甲醇 、 水 为溶剂， 反应 3.17h， 生成 (2R)-2-羟基戊二酸二甲酯
  参考文献：
  名称：

  蜡样芽孢杆菌Ch HF-PS细胞壁三糖重复单元的首次合成

  摘要：

  据报道，Ch HF-PS是蜡状芽孢杆菌的细胞壁三糖重复单元，它是第一个全合成的。合成的三糖在还原末端附加了一个氨基丙基接头，以便与蛋白质和微阵列偶联。收敛合成涉及关键步骤，其中包括将d-甘露糖转化为正交保护的稀有AAT糖结构单元，两个连续的α-立体选择性糖基化，通过溶剂参与的连接子的β-选择性连接以及酰胺键的形成。

  DOI：

  10.1021/ol5021527
• 作为产物：
  描述：

  D-谷氨酸 在 盐酸 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 生成 tert-butyl (R)-5-oxotetrahydrofuran-2-carboxylate
  参考文献：
  名称：

  蜡样芽孢杆菌Ch HF-PS细胞壁三糖重复单元的首次合成

  摘要：

  据报道，Ch HF-PS是蜡状芽孢杆菌的细胞壁三糖重复单元，它是第一个全合成的。合成的三糖在还原末端附加了一个氨基丙基接头，以便与蛋白质和微阵列偶联。收敛合成涉及关键步骤，其中包括将d-甘露糖转化为正交保护的稀有AAT糖结构单元，两个连续的α-立体选择性糖基化，通过溶剂参与的连接子的β-选择性连接以及酰胺键的形成。

  DOI：

  10.1021/ol5021527

文献信息

• Development of a Multigram Asymmetric Synthesis of 2-(<i>R</i>)-2-(4,7,10-Tris <i>tert</i>-Butylcarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic Acid, 1-<i>tert</i>-Butyl Ester, (<i>R</i>)-<i>tert</i>-Bu₄-DOTAGA
  作者：Stuart G. Levy、Vincent Jacques、Kevin Li Zhou、Shirley Kalogeropoulos、Kelly Schumacher、John C. Amedio、Jonathan E. Scherer、Steven R. Witowski、Richard Lombardy、Karsten Koppetsch

  DOI：10.1021/op8002932

  日期：2009.5.15

  A process for the multigram asymmetric synthesis of the chiral tetraazamacrocycle 2-(R)-2-(4,7,10-tris tert-butylcarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1-tert-butyl ester ((R)-tert-Bu4-DOTAGA, 4) has been devised and demonstrated. The nine-step synthesis features an improved synthesis of 2-(S)-5-oxotetrahydrofuran-2-carboxylic acid, tert-butyl ester 8, the precursor to the

  手性四氮杂大环2-（R）-2-（4,7,10-三叔丁基丁基羧甲基-1,4,7,10-四氮杂环十二烷基-1-基）-戊二酸的多克不对称合成方法1 -叔丁基酯（（[R ）-叔-Bu 4 -DOTAGA，4）已经设计和展示。九步合成法改进了2-（S）-5-氧代四氢呋喃-2-羧酸叔丁酯8的合成，该酯是新型烷基化剂（S）-5-苄基1-叔丁基的前体2-（甲基磺酰氧基）戊二酸酯12，用于以高光学纯度将正交保护的手性谷氨酸臂引入1,4,7,10-四氮杂环十二烷（环）核。环烯衍生物（[R ）-吨-Bu 4 -DOTAGA，4，一种用于磁共振成像中的用途的关键中间体（MRI）的候选，以高化学（≥95％）和光（EE≥97％）纯度产生。开发的方法成功地应用于的千克规模的cGMP合成（- [R ） -吨-Bu 4 -DOTAGA。
• Enantioselective Syntheses of (R)- and (S)-Hexahydropyridazine-3-carboxylic Acid Derivatives
  作者：Ulrich Schmidt、Christine Braun、Heinz Sutoris

  DOI：10.1055/s-1996-4192

  日期：1996.2

  Appropriately protected optically active tetrahydropyridazine-3-carboxylic acid and hexahydropyridazine-3-carboxylic acid were prepared via ring closure of α-hydrazino- and δ-hydrazinopentanoates. Either optically active glutamic acid or an enantioselective catalytic hydrogenation was used to generate the chiral center. The numerous optically active intermediates are valuable starting materials for the synthesis of other unusual amino acids.

  通过δ-肼和δ-肼戊酸酯的闭环反应，制备了适当保护的光学活性四氢哒嗪-3-羧酸和六氢哒嗪-3-羧酸。光学活性谷氨酸或对映体选择性催化加氢均可用于生成手性中心。这些具有光学活性的中间体是合成其他不常见氨基酸的宝贵起始原料。
• Synthesis and Evaluation of ⁶⁸Ga- and ¹⁷⁷Lu-Labeled (<i>R</i>)- vs (<i>S</i>)-DOTAGA Prostate-Specific Membrane Antigen-Targeting Derivatives
  作者：Ruiyue Zhao、Karl Ploessl、Zhihao Zha、Seokrye Choi、David Alexoff、Lin Zhu、Hank F. Kung

  DOI：10.1021/acs.molpharmaceut.0c00777

  日期：2020.12.7

  uptake, and biodistribution between the two isomers was performed. Radiolabeling of (R)-[177Lu]Lu-13 and (S)-[177Lu]Lu-13 at 50 °C suggested that rates of complex formation were time-dependent and the formation of (S)-[177Lu]Lu-13 was distinctly faster. The rates of complex formation for the corresponding 68Ga agents were comparable between structural isomers. The natGa and natLu equivalents showed high

  前列腺特异性膜抗原 (PSMA) 在前列腺癌细胞中过度表达，因此是前列腺癌诊断和放射性核素治疗的一个有吸引力的目标。最近，发表了使用新型 PSMA 靶向 PET 显像剂 [ 68 Ga]Ga-PSMA-093 ([ 68 Ga]Ga-HBED-CC- O-羧甲基-Tyr-CO-NH-Glu) 的临床研究结果，支持开发这种用于诊断前列腺癌的药物。在这项研究中，PSMA-093 中的 HBED-CC 螯合基团被立体选择性 ( R )- 或 ( S )-DOTAGA 取代。该螯合基团不仅用于螯合68Ga 但也可用于络合其他放射性金属以进行放射性核素治疗。相应的光学纯 ( R )- 和 ( S )-[ 68 Ga/ 177 Lu]-DOTAGA 衍生物， ( R )-[ 68 Ga/ 177 Lu]- 13和 ( S )-[ 68 Ga/ 177 Lu]- 13、准备成功。对两种异构体之间的放射性
• 5,5-Dialkyl-δ-valerolactone Derivatives as New Chirai Dopants for Ferroelectric Liquid Crystals
  作者：Keiichi Sakashita、Yuriko Nakaoka、Tetsuya Ikemoto、Fumiko Terada、Yoshitaka Kageyama、Mizuo Shindo、Kenji Mori

  DOI：10.1246/cl.1991.1727

  日期：1991.10

  (S)-2-(4′-Octyloxybiphenyl-4-carboxy)-5,5-dipropyl-δ-valerolactone showed interesting properties as the chiral dopant for ferroelectric liquid crystals (FLCs). The FLC mixture containing only 2% by mol of this compound exhibited the magnitude of spontaneous polarization (Ps) as large as 9.6 nC/cm2 and the response time as fast as 75 μs at 25 °C in the electric field of ±5 V/μm.

  (S)-2-(4'-Octyloxybiphenyl-4-carboxy)-5,5-dipropyl-δ-valerolactone 作为铁电液晶 (FLC) 的手性掺杂剂显示出有趣的特性。仅含有 2% mol 的这种化合物的 FLC 混合物表现出高达 9.6 nC/cm2 的自发极化 (Ps) 幅度和在 25 °C 和 ±5 V/微米。
• Enantiopure bifunctional chelators for copper radiopharmaceuticals – Does chirality matter in radiotracer design?
  作者：Ajay N. Singh、Marianna Dakanali、Guiyang Hao、Saleh Ramezani、Amit Kumar、Xiankai Sun

  DOI：10.1016/j.ejmech.2014.04.071

  日期：2014.6

  It is well recognized that carbon chirality plays a critical role in the design of drug molecules. However, very little information is available regarding the effect of stereoisomerism of macrocyclic bifunctional chelators (BFC) on biological behaviors of the corresponding radiopharmaceuticals. To evaluate such effects, three enantiopure stereoisomers of a copper radiopharmaceutical BFC bearing two chiral carbon atoms were synthesized in forms of R,R-, S,S-, and R,S-. Their corresponding peptide conjugates were prepared by coupling with a model peptide sequence, c(RGDyK), which targets the αvβ3 integrin for in vitro and in vivo evaluation of their biological behaviors as compared to the racemic conjugate. Despite the chirality differences, all the conjugates showed a similar in vitro binding affinity profile to the αvβ3 integrin (106, 108, 85 and 100 nM for rac-H2-1, RR-H2-1, SS-H2-1, and RS-H2-1 respectively with all p values > 0.05) and a similar level of in vivo tumor uptake (2.72 ± 0.45, 2.60 ± 0.52, 2.45 ± 0.48 and 2.88 ± 0.59 for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 at 1 h p.i. respectively). Furthermore, they demonstrated a nearly identical biodistribution pattern in major organs (e.g. 2.07 ± 0.21, 2.13 ± 0.58, 1.70 ± 0.20 and 1.90 ± 0.46 %ID/g at 24 h p.i. in liver for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 respectively; 1.80 ± 0.46, 2.30 ± 1.49, 1.73 ± 0.31 and 2.23 ± 0.71 at 24 h p.i. in kidneys for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 respectively). Therefore we conclude that the chirality of BFC plays a negligible role in αvβ3-targeted copper radiopharmaceuticals. However, we believe it is still worthwhile to consider the chirality effects of BFCs on other targeted imaging or therapeutic agents.