(2R,3S)-1-(叔丁氧羰基)-3-氟吡咯烷-2-羧酸 | 330945-23-8

• 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
• 中文名称: (2R,3S)-1-(叔丁氧羰基)-3-氟吡咯烷-2-羧酸
• 英文名称: (2R,3S)-1-tert-butoxycarbonyl-3-fluoro-pyrrolidine-2-carboxylic acid
• 英文别名: N-tert-butyloxycarbonyl-trans-3-fluoro-L-proline；(2R,3S)-1-(tert-Butoxycarbonyl)-3-fluoropyrrolidine-2-carboxylic acid；(2R,3S)-3-fluoro-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
• CAS: 330945-23-8
• 化学式: C₁₀H₁₆FNO₄
• 分子量: 233.24
• InChiKey: BUNHNBQISAFFOR-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S)-1-(叔丁氧羰基)-3-氟吡咯烷-2-羧酸 在 lithium aluminium tetrahydride 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 tert-butyl 4-[7-[6-[bis[(4-methoxyphenyl)methyl]amino]-3-(trifluoromethyl)-2-pyridyl]-6-chloro-2- [[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]methoxy]quinazolin-4-yl]piperazine-1-carboxylate
  参考文献：
  名称：

  [EN] FUSED RING COMPOUNDS
  [FR] COMPOSÉS CYCLIQUES FONDUS

  摘要：

  公开号：

  WO2020097537A3
• 作为产物：
  描述：

  Boc-顺式-3-羟基-L-脯氨酸 在 palladium on activated charcoal 氢气 、 caesium carbonate 、 三氟化硫吗啉 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3S)-1-(叔丁氧羰基)-3-氟吡咯烷-2-羧酸
  参考文献：
  名称：

  Stereoelectronic and Steric Effects in the Collagen Triple Helix:  Toward a Code for Strand Association

  摘要：

  Collagen is the most abundant protein in animals. The protein consists of a helix of three strands, each with sequence X-Y-Gly. Natural collagen is most stable when X is (2S)-proline (Pro) and Y is (2S,4R)-4-hydroxyproline (4R-Hyp). We had shown previously that triple helices in which X is (2S,4S)-4-fluoroproline (4S-Flp) or Y is (2S,4R)-4-fluoroproline (4R-Flp) display hyperstability. This hyperstability arises from stereoelectronic effects that preorganize the main-chain dihedral angles in the conformation found in the triple helix. Here, we report the synthesis of strands containing both 4S-Flp in the X-position and 4R-Flp in the Y-position. We find that these strands do not form a stable triple helix, presumably because of an unfavorable steric interaction between fluoro groups on adjacent strands. Density functional theory calculations indicate that (2S,3S)-3-fluoroproline (3S-Flp), like 4S-Flp, should preorganize the main chain properly for triple-helix formation but without a steric conflict. Synthetic strands containing 3S-Flp in the X-position and 4R-Flp in the Y-position do form a triple helix. This helix is, however, less stable than one with Pro in the X-position, presumably because of an unfavorable inductive effect that diminishes the strength of the interstrand 3S-FlpC=(OH)-H-...-NGly hydrogen bond. Thus, other forces can counter the benefits derived from the proper preorganization. Although (Pro-Pro-Gly)(7) and (4S-Flp-4R-Flp-Gly)(7) do not form stable homotrimeric helices, mixtures of these two peptides form stable heterotrimeric helices containing one (Pro-Pro-Gly)(7) strand and two (4S-Flp-4R-Flp-Gly)(7) strands. This stoichiometry can be understood by considering the cross sections of the two possible heterotrimeric helices. This unexpected finding portends the development of a "code" for the self-assembly of determinate triple helices from two or three strands.

  DOI：

  10.1021/ja054674r

文献信息

• [EN] FLUOROHYDROXYPROLINE DERIVATIVES USEFUL IN THE PREPARATION OF PROTEOLYSIS TARGETED CHIMERAS<br/>[FR] DÉRIVÉS DE FLUOROHYDROXYPROLINE UTILES DANS LA PRÉPARATION DE CHIMÈRES CIBLÉES PAR PROTÉOLYSE
  申请人：UNIV DUNDEE

  公开号：WO2018051107A1

  公开（公告）日：2018-03-22

  There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, and to their utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for their preparation thereof, and use in medicine. There is particularly provided novel small molecule E3 ubiquitin ligase protein binding inhibitorcompounds based on a fluorohydroxyproline scaffold, to their utility as ligands in synthesizing novel PROTACs, and to synthetic methods therefor.

  提供了新型小分子E3泛素连接酶蛋白结合配体化合物，以及它们在蛋白质降解靶向嵌合物（PROTACs）中的用途，以及其制备的过程，以及在医学中的用途。特别提供了基于氟羟脯氨酸支架的新型小分子E3泛素连接酶蛋白结合抑制剂化合物，以及它们作为配体在合成新型PROTACs中的用途，以及用于此目的的合成方法。
• [EN] INDOLE COMPOUNDS OR ANALOGUES THEREOF USEFUL FOR THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION (AMD)<br/>[FR] COMPOSÉS INDOLIQUES OU ANALOGUES DE CEUX-CI UTILES DANS LE TRAITEMENT DE LA DÉGÉNÉRESCENCE MACULAIRE LIÉE À L'ÂGE (DMLA)
  申请人：NOVARTIS AG

  公开号：WO2012093101A1

  公开（公告）日：2012-07-12

  The present invention provides a compound of formula (I): a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种公式(I)的化合物：一种制造本发明化合物的方法及其治疗用途。本发明进一步提供了一种药物活性剂的组合物和一种药物组合物。
• Synthesis of optically pure N-Boc-protected (2R,3R)- and (2R,3S)-3-fluoroprolines
  作者：Luc Demange、Jérôme Cluzeau、André Ménez、Christophe Dugave

  DOI：10.1016/s0040-4039(00)02030-x

  日期：2001.1

  Non-protein amino acids (2R,3R)- and (2R,3S)-3-fluoroprolines were synthesized as novel probes for studying the cis/trans isomerization of the amino acylproline peptide bond. The N-Boc-protected target compounds were obtained as optically pure material starting from (2S,3S)-3-hydroxyproline.

  合成了非蛋白质氨基酸（2 R，3 R）-和（2 R，3 S）-3-氟脯氨酸，作为研究氨基酰基脯氨酸肽键顺式/反式异构化的新型探针。所述Ñ作为由式（2光学纯的起始材料获得-Boc保护的目标化合物小号，3小号）-3-羟脯氨酸。
• 3S-Fluoroproline as a probe to monitor proline isomerization during protein folding by 19F-NMR
  作者：Colin A. Thomas、Erach R. Talaty、James G. Bann

  DOI：10.1039/b821952d

  日期：——

  Variable-temperature inversion transfer NMR is used to determine the kinetic and thermodynamic parameters of cis–transisomerization of N-Ac-(3R) and (3S)-fluoroproline-OMe.

  可变温度反转转移核磁共振（NMR）用于确定N-Ac-(3R)和(3S)-氟脯氨酸-OMe的顺反异构化的动力学和热力学参数。
• Complement pathway modulators and uses thereof
  申请人：ALTMANN Eva

  公开号：US20120295884A1

  公开（公告）日：2012-11-22

  The present invention provides a compound of formula I: a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种化合物I的方法，用于制造本发明的化合物以及其治疗用途。本发明还提供了一种药理活性剂的组合和制药组合物。