(S)-4-benzyl-3-(4,4,4-trifluorobutanoyl)oxazolidin-2-one | 669074-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (S)-4-benzyl-3-(4,4,4-trifluorobutanoyl)oxazolidin-2-one
• 英文别名: (4S)-4-Benzyl-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolidin-2-one；(4S)-4-benzyl-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolidin-2-one
• CAS: 669074-41-3
• 化学式: C₁₄H₁₄F₃NO₃
• 分子量: 301.265
• InChiKey: XPGZSCXWDAPVIM-NSHDSACASA-N

物化性质

• 沸点：
  395.8±42.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-4-benzyl-3-(4,4,4-trifluorobutanoyl)oxazolidin-2-one 在 PhSO₂N[OCH(Ph)-(S)] 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 以100%的产率得到
  参考文献：
  名称：

  P3 cap modified Phe*-Ala series BACE inhibitors

  摘要：

  With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3 NHBoc moiety as seen in 3 with other polar functional groups such as amino, hydroxyl and fluorine. Several promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19) demonstrated good enzyme inhibitory potencies (BACE-1 IC50 < 50 nM) and whole cell activities (IC50 similar to 1 muM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.085
• 作为产物：
  描述：

  (S)-4-苄基-2-唑烷酮 在 ytterbium(III) triflate hydrate 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (S)-4-benzyl-3-(4,4,4-trifluorobutanoyl)oxazolidin-2-one
  参考文献：
  名称：

  Conjugate hydrotrifluoromethylation of α,β-unsaturated acyl-oxazolidinones: synthesis of chiral fluorinated amino acids

  摘要：

  描述了一种新颖的共轭氢氟烷基化α,β-不饱和酰基噁唑烷酮的方法。利用该方法，制备了手性纯的β-三氟甲基化氨基酸。三氟瓦林和三氟异亮氨酸被引入到肽中，发现其α-螺旋倾向极低。

  DOI：

  10.1039/c2ob26810h

文献信息

• CYCLIC TETRAMER COMPOUNDS AS PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) INHIBITORS FOR THE TREATMENT OF METABOLIC DISORDERS
  申请人：NOVARTIS AG

  公开号：US20200164024A1

  公开（公告）日：2020-05-28

  The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , X 1 , X 2 , and X 3 are described herein.

  该披露涉及对PCSK9的抑制剂，用于治疗胆固醇脂质代谢以及其他PCSK9发挥作用的疾病，其化学式为(I)： 或其药用可接受的盐、水合物、溶剂合物、前药、立体异构体、N-氧化物或互变异构体，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、X1、X2和X3如本文所述。
• Enantioselective Synthesis and Biological Evaluation of Sanglifehrin A and B and Analogs
  作者：Chia‐Fu Chang、Hope A. Flaxman、Christina M. Woo

  DOI：10.1002/anie.202103022

  日期：2021.7.26

  and B are immunosuppressive macrocyclic natural products endowed with and differentiated by a unique spirocyclic lactam. Herein, we report an enantioselective total synthesis and biological evaluation of sanglifehrin A and B and analogs. Access to the spirocyclic lactam was achieved through convergent assembly of a key pyranone intermediate followed by a stereo-controlled spirocyclization. The 22-membered

  Sanglifehrin A 和 B 是免疫抑制性大环天然产物，具有独特的螺环内酰胺并由其区分。在此，我们报告了 sanglifehrin A 和 B 以及类似物的对映选择性全合成和生物学评价。获得螺环内酰胺是通过关键的吡喃酮中间体的会聚组装，然后是立体控制的螺环化来实现的。22 元大环核是在 2,6-双（三氟甲基）苯硼酸 (BFBB) 存在下通过闭环复分解合成的。螺环内酰胺和大环片段通过Stille偶联结合，以提供相思蛋白A和B。另外制备在C40位置具有变化的其它相思蛋白B类似物。生物学评价表明，2-CF 3在 Jurkat 细胞中，sanglifehrin B 的类似物表现出比天然产物 sanglifehrin A 和 B 更高的抗增殖活性。两种天然产物均诱导亲环蛋白 A (CypA) 的高阶同二聚化，但只有 sanglifehrin A 促进 CypA 与肌苷-5'-单磷酸脱氢酶 2
• Synthesis of enantiomerically pure (2<i>S</i>,3<i>S</i>)-5,5,5-trifluoroisoleucine and (2<i>R</i>,3<i>S</i>)-5,5,5-trifluoro-<i>allo</i>-isoleucine
  作者：Holger Erdbrink、Elisabeth K Nyakatura、Susanne Huhmann、Ulla I M Gerling、Dieter Lentz、Beate Koksch、Constantin Czekelius

  DOI：10.3762/bjoc.9.236

  日期：——

  A practical route for the stereoselective synthesis of (2S,3S)-5,5,5-trifluoroisoleucine (L-5-F₃Ile) and (2R,3S)-5,5,5-trifluoro-allo-isoleucine (D-5-F₃-allo-Ile) was developed. The hydrophobicity of L-5-F₃Ile was examined and it was incorporated into a model peptide via solid phase peptide synthesis to determine its α-helix propensity. The α-helix propensity of 5-F₃Ile is significantly lower than Ile, but surprisingly high when compared with 4’-F₃Ile.

  开发了一种立体选择性合成(2S,3S)-5,5,5-三氟异亮氨酸(L-5-F3Ile)和(2R,3S)-5,5,5-三氟-异亮氨酸(D-5-F3-allo-Ile)的实用路线。检查了L-5-F3Ile的亲水性，并通过固相肽合成将其并入模型肽中，以确定其α-螺旋倾向性。与Ile相比，5-F3Ile的α-螺旋倾向性显著降低，但与4'-F3Ile相比则令人惊讶地高。
• Cyclic tetramer compounds as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for the treatment of metabolic disorders
  申请人：NOVARTIS AG

  公开号：US11026993B2

  公开（公告）日：2021-06-08

  The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein R1, R1, R1, R1, R1, R1, R1, R1, R1, X1, X2, and X3 are described herein.

  本公开涉及可用于治疗胆固醇脂质代谢和 PCSK9 在其中起作用的其他疾病的 PCSK9 抑制剂，其具有式 (I)： 或其药学上可接受的盐、水合物、溶液剂、原药、立体异构体、N-氧化物或同系物，其中 R1、R1、R1、R1、R1、R1、R1、X1、X2 和 X3 在本文中描述。
• Stereoselective Synthesis of Fluoroalkylated Butanolides
  作者：Constantin Czekelius、Holger Erdbrink

  DOI：10.1055/s-0033-1339755

  日期：——

  Starting from fluoroalkylated, optically active acyl oxazolidinones the corresponding di- and trisubstituted butanolides were prepared in enantiomerically pure form. Using a divergent synthetic route highly functionalized fluoroalkylated building blocks are accessible.