(3S)-benzyloxy-1-(tert-butoxycarbonyl)pyrrolidine-(2S)-carboxylic acid | 902770-49-4

• 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: (3S)-benzyloxy-1-(tert-butoxycarbonyl)pyrrolidine-(2S)-carboxylic acid
• 英文别名: (3S)-3-(benzyloxy)-1-(tert-butoxycarbonyl)-L-proline；boc-o-benzyl-L-hydroxyproline；(2S,3S)-1-[(2-methylpropan-2-yl)oxycarbonyl]-3-phenylmethoxypyrrolidine-2-carboxylic acid
• CAS: 902770-49-4
• 化学式: C₁₇H₂₃NO₅
• 分子量: 321.373
• InChiKey: KUSMJYMRRJDJCA-KBPBESRZSA-N

物化性质

• 沸点：
  461.3±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S)-benzyloxy-1-(tert-butoxycarbonyl)pyrrolidine-(2S)-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 ethyl [4-[(3S)-benzyloxy-1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-(2S)-pyrrolidinylcarbonyl]-1-piperazinyl]acetate
  参考文献：
  名称：

  Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists

  摘要：

  A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12ml/min/kg and 11p 9ml/min/kg). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.058
• 作为产物：
  描述：

  methyl (3S)-benzyloxy-1-(tert-butoxycarbonyl)pyrrolidine-(2S)-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以100%的产率得到(3S)-benzyloxy-1-(tert-butoxycarbonyl)pyrrolidine-(2S)-carboxylic acid
  参考文献：
  名称：

  Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists

  摘要：

  A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12ml/min/kg and 11p 9ml/min/kg). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.058

文献信息

• 1-(CYCLOALKYL-CARBONYL)PROLINE DERIVATIVE
  申请人：SUMITOMO DAINIPPON PHARMA CO., LTD.

  公开号：US20150210640A1

  公开（公告）日：2015-07-30

  A compound represented by formula (1) (in the formula: ring-D represents a three- to eight-membered hydrocarbon ring; R a represents an optionally substituted amino C 1-6 alkyl group or the like; R b1 and R b2 each independently represent a hydrogen atom, a halogen atom, or the like; R c represents an optionally substituted C 6-10 aryl group or the like; R d represents a hydrogen atom or the like; and ring-Q represents a (hetero)aryl group or the like which may be substituted with a carboxyl group or the like) or a pharmaceutically acceptable salt thereof exhibits an excellent FXIa inhibitory activity, and is useful as a therapeutic agent against thrombosis or the like.

  化合物的化学式为（1）（其中，环D代表3-8个碳原子的碳氢环；R代表可选择性取代的氨基C1-6烷基或类似物；Rb1和Rb2各自独立地代表氢原子、卤素原子或类似物；Rc代表可选择性取代的C6-10芳基或类似物；Rd代表氢原子或类似物；环Q代表（杂）芳基或类似物，可被羧基或类似物取代），或其药学上可接受的盐，具有出色的FXIa抑制活性，可用作治疗血栓或类似疾病的治疗剂。
• Limosilactobacillus (Lactobacillus) fermentum ALAL020, a Probiotic Candidate Bacterium, Produces a Cyclic Dipeptide That Suppresses the Periodontal Pathogens Porphyromonas gingivalis and Prevotella intermedia
  作者：Tomomi Kawai、Tomoko Ohshima、Takeshi Tanaka、Satoshi Ikawa、Atsushi Tani、Naoya Inazumi、Ryoichi Shin、Yukie Itoh、Karen Meyer、Nobuko Maeda

  DOI：10.3389/fcimb.2022.804334

  日期：——

  Periodontal disease develops as a result of oral microbiota in dysbiosis, followed by the growth of periodontal pathogens such as Porphyromonas gingivalis and Prevotella intermedia. In case of acute symptoms, antibacterial agents and disinfectants are administered, however the appearance of drug-resistant bacteria and allergies cause problems. In recent years, studies on the effects of probiotics have been conducted as an alternative therapy for periodontitis. However, the basic mechanism of the inhibitory effect of probiotic bacteria on periodontal disease has not been clearly elucidated. To clarify the antibacterial mechanism of probiotics against periodontal pathogens, we used Limosilactobacillus (Lactobacillus) fermentum ALAL020, which showed the strongest antibacterial activity against P. gingivalis and P. intermedia among 50 screened lactic acid bacteria strains. The antibacterial substances produced were identified and structurally analyzed. After neutralizing the MRS liquid culture supernatant of ALAL020 strain, the molecular weight (m/z) of the main antibacterial substance separated by gel filtration column chromatography and reverse phase HPLC was 226.131. This low molecular weight compound was analyzed by LC-MS and disclosed the composition formula C₁₁H₁₈O₃N₂, however the molecular structure remained unknown. Then, structural analysis by NMR revealed C₁₁H₁₈O₃N₂ as the cyclic dipeptide, “hexahydro-7-hydroxy-3- (2-methylpropyl) pyrrolo [1,2-a] pyrazine-1,4-dion cyclo (Hyp-Leu) “. Based on the results of this analysis, cyclo (Hyp-Leu) was chemically synthesized and the antibacterial activity against P. gingivalis and P. intermedia was measured. The minimum inhibitory concentration (MIC) was 2.5 g/L and the minimum bactericidal concentration (MBC) was shown to be less than 5 g/L. In addition, an in vitro epithelial tissue irritation test at 10 g/L showed no tissue toxicity. So far there are no reports of this peptide being produced by probiotic bacteria. Furthermore, antibacterial activity of this cyclic dipeptide against periodontal disease bacteria has not been confirmed. The results of this study might lead to a comprehensive understanding of the antibacterial mechanism against periodontal disease bacteria in future, and are considered applicable for the prevention of periodontal disease.

  牙周疾病是由口腔微生物群落失调引起的，随后是牙周病原菌（如牙龈卟啉菌和中间丛菌）的增长。在急性症状的情况下，会使用抗菌剂和消毒剂，但耐药菌和过敏引起问题。近年来，对益生菌治疗牙周炎的影响进行了研究作为替代疗法。然而，益生菌对牙周疾病的抑制作用的基本机制尚未得到明确阐明。为了阐明益生菌对牙周病原菌的抗菌机制，我们使用了50个筛选的乳酸菌菌株中对牙龈卟啉菌和中间丛菌的抗菌活性最强的LimosiLActobacillus (LActobacillus) fermentum ALAL020。已经确定并结构分析了产生的抗菌物质。在中和ALAL020菌株的MRS液体培养上清液后，通过凝胶过滤柱层析和反相高效液相色谱法分离的主要抗菌物质的分子量（m/z）为226.131。这种低分子量化合物通过LC-MS分析，揭示了C11H18O3N2的组成式，但分子结构仍未知。然后，通过NMR的结构分析，发现C11H18O3N2是环状二肽“六氢-7-羟基-3-（2-甲基丙基）吡咯[1,2-a]吡嗪-1,4-二酮环（Hyp-Leu）”。根据这种分析的结果，合成了环（Hyp-Leu），并测量了其对牙龈卟啉菌和中间丛菌的抗菌活性。最小抑菌浓度（MIC）为2.5 g / L，最小杀菌浓度（MBC）小于5 g / L。此外，10 g / L的体外上皮组织刺激试验未显示组织毒性。迄今为止，没有报道益生菌产生这种肽。此外，这种环状二肽对牙周疾病细菌的抗菌活性尚未得到确认。本研究的结果可能导致未来对牙周疾病细菌的抗菌机制的全面了解，并被认为适用于预防牙周疾病。
• US9758480B2
  申请人：——

  公开号：US9758480B2

  公开（公告）日：2017-09-12