(2S,4R)-1-(4-Tolylsulfonyl)-2-(((4-tolylsulfonyl)oxy)methyl)-4-((4-tolylsulfonyl)oxy)pyrrolidine | 5234-75-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,4R)-1-(4-Tolylsulfonyl)-2-(((4-tolylsulfonyl)oxy)methyl)-4-((4-tolylsulfonyl)oxy)pyrrolidine
• 英文别名: (2S,4R)-N-Tosyl-4-tosyloxy-2-tosyloxymethylpyrrolidine；(2S,4R)-1-(4-tolylsulfonyl)-4-<(4-tolylsulfonyl)oxy>-2-<<(4-tolylsulfonyl)oxy>methyl>pyrrolidine；(2S,4R)-1,4-bis(tosyl)-2-(tosylmethyl)pyrrolidine；trans-1-Tosyl-2-(tosyloxymethyl)-4-tosyloxypyrrolidin；(2S,4R)-1-(4-Toluenesulfonyl)-2-(4-toluenesulfonyloxy-methyl)-4-(4-toluenesulfonyloxy)-pyrrolidine；(2S,4R)-1-(p-tolylsulphonyl)-4-[(p-tolylsulphonyl)oxy]-2-pyrrolidinylmethyl p-toluenesulphonate；1-(toluene-4-sulfonyl)-4-(toluene-4-sulfonyloxy)-2-(toluene-4-sulfonyloxymethyl)-pyrrolidine；(2S,4R)-N,O-Ditosyl-4-tosyloxyprolinol；(2S, 4R)-1-(4-toluenesulfonyl)-2-(p-toluenesulfonyl-oxymethyl)-4-(4-toluenesulfonyloxy)-pyrrolidine；[(2S,4R)-1-(4-methylphenyl)sulfonyl-4-(4-methylphenyl)sulfonyloxypyrrolidin-2-yl]methyl 4-methylbenzenesulfonate
• CAS: 5234-75-3
• 化学式: C₂₆H₂₉NO₈S₃
• 分子量: 579.716
• InChiKey: UJDJLZINFVKBBH-XZOQPEGZSA-N

物化性质

• 熔点：
  135-136 °C
• 沸点：
  740.5±70.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  149
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S,4R)-1-(4-Tolylsulfonyl)-2-(((4-tolylsulfonyl)oxy)methyl)-4-((4-tolylsulfonyl)oxy)pyrrolidine 在 氢溴酸 、 sodium methylate 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 2-(苯基甲基)-2,5-二氮杂双环环[2.2.1]庚烷(1s,4s)-(9ci)
  参考文献：
  名称：

  Multicomponent synthesis of some new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro anti-proliferative activity against CaSki, MDA-MB-231 and SK-Lu-1 tumour cells as apoptosis inducing agents without necrosis

  摘要：

  Identification of a new class of antitumor agent capable to induce apoptosis without triggering necrotic cell death event is challenging. The present communication describes the multicomponent synthesis of seven new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro antiproliferative activity on cervical cancer cell line (CaSki), breast cancer cell line (MDA-MB231), lung cancer cell line (SK-Lu-1) and human lymphocytes. Among the synthesized dithiocarbamates, compound 9e displayed significant antiproliferative activity without inducing any necrotic cell death (both on tumour cells and lymphocytes) and induced apoptosis in tumor cells by the caspase dependent apoptotic pathway. The compound 9e also exhibited greater tumor selectivity than human lymphocytes. In silico ADME predictions revealed that compound 9e has the potential to be developed as a drug candidate. Rapid chemical modifications of this lead are thus highly necessary for further investigation as a drug like safer antitumor candidate and also to achieve compounds with better activity profile.

  DOI：

  10.1080/14756366.2017.1363197
• 作为产物：
  描述：

  N-tosyl-trans-4-hydroxy-L-proline 在 吡啶 、 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 82.0h， 生成 (2S,4R)-1-(4-Tolylsulfonyl)-2-(((4-tolylsulfonyl)oxy)methyl)-4-((4-tolylsulfonyl)oxy)pyrrolidine
  参考文献：
  名称：

  Synthesis of (1R,4R)- and (1S,4S)-2,5-Diazabicyclo[2.2.1]heptanes and TheirN-Substituted Derivatives

  摘要：

  (1R,4R)-和(1S,4S)-2,5-二氮杂双环[2.2.1]庚烷环系的衍生物以对映体纯形式从反式-4-羟基-L-脯氨酸（2）中制备而成。目标化合物是抗菌喹啉羧酸的前体。

  DOI：

  10.1055/s-1990-27056

文献信息

• [EN] INHIBITORS OF THE BCL6 BTB DOMAIN PROTEIN-PROTEIN INTERACTION AND USES THEREOF<br/>[FR] INHIBITEURS DE L'INTERACTION PROTÉINE-PROTÉINE DU DOMAINE BCL6 BTB ET LEURS UTILISATIONS
  申请人：ONTARIO INSTITUTE FOR CANCER RES OICR

  公开号：WO2019153080A1

  公开（公告）日：2019-08-15

  The present application relates to compounds of Formula I (I) or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, and various uses in the treatment of diseases, disorders or conditions that are treatable by inhibiting interactions with BCL6 BTB, such as cancer.

  本申请涉及公式I（I）化合物或其药用可接受的盐、溶剂化合物和/或前药，包括含有这些化合物或药用可接受的盐、溶剂化合物和/或前药的组合物，以及在治疗可通过抑制与BCL6 BTB的相互作用可治疗的疾病、紊乱或状况中的各种用途，如癌症。
• Rhodium complexes of chiral phosphines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04539411A1

  公开（公告）日：1985-09-03

  Novel chiral phosphines are disclosed which when complexed with rhodium provide catalyst compositions for asymmetric hydrogenations.

  揭示了一种新型手性膦化合物，当与铑形成配合物时，可提供用于不对称氢化的催化剂组合物。
• Synthesis of Novel Derivatives of (1S,4S)-2,5-Diazabicyclo[2.2.1]heptane and Their Evaluation as Potential Ligands in Asymmetric Catalysis
  作者：Roberto Melgar-Fernández、Rodrigo González-Olvera、J. Luis Olivares-Romero、Vianney González-López、Leticia Romero-Ponce、María del Refugio Ramírez-Zárate、Patricia Demare、Ignacio Regla、Eusebio Juaristi

  DOI：10.1002/ejoc.200700785

  日期：2008.2

  for the enantioselective addition of diethylzinc to aldehydes and as chiral Lewis acid activators in the asymmetric Diels–Alder reaction. In the former system, diamine 30 induced up to 92 % enantiomeric excess in the formation of (S)-phenyl ethyl carbinol, whereas in the case of the cycloaddition reaction between cyclopentadiene and 3-acryloyloxazolidin-2-one the catalytic complex formed between dimeric

  从 (S)-反式-4-羟脯氨酸制备 (1S,4S)-2,5-二氮杂双环 [2.2.1] 庚烷 (2-36, 38, 39) 的 37 种（大多数是新型）手性衍生物. 选择了这些手性配体，作为制备二乙基锌与醛的对映选择性加成催化剂的潜在配体，以及作为不对称 Diels-Alder 反应中的手性路易斯酸活化剂的潜在配体。在前一个系统中，二胺 30 在 (S)-苯基乙基甲醇的形成中诱导了高达 92% 的对映体过量，而在环戊二烯和 3-丙烯酰恶唑烷-2-one 之间的环加成反应的情况下，二聚体之间形成的催化复合物衍生物 8 和三氟甲磺酸铜 [Cu(OTf)2] 以 95:5 的内/外比提供预期产物，主要非对映异构产物的 ee 高达 72%。最后，在这项工作中制备的一些新型手性二胺也被评估为 α-苯基-α-氰基乙酸乙酯不对称胺化的潜在有机催化剂。双功能衍生物 12 以优异的收率和高达 40% 的 ee
• Hydroxyproline-Derived Pseudoenantiomeric [2.2.1] Bicyclic Phosphines: Asymmetric Synthesis of (+)- and (−)-Pyrrolines
  作者：Christopher E. Henry、Qihai Xu、Yi Chiao Fan、Tioga J. Martin、Lee Belding、Travis Dudding、Ohyun Kwon

  DOI：10.1021/ja505592h

  日期：2014.8.27

  We have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]heptanes from naturally occurring trans-4-hydroxy-l-proline in six chemical operations. These syntheses are concise and highly efficient, with straightforward purification. When we used these chiral phosphines as catalysts for reactions of γ-substituted allenoates with imines, we obtained enantiomerically enriched pyrrolines in

  我们在六种化学操作中从天然存在的反式-4-羟基-l-脯氨酸制备了两种新的非对映异构体 2-aza-5-phosphabicyclo[2.2.1] 庚烷。这些合成简洁高效，纯化简单。当我们使用这些手性膦作为 γ-取代的烯丙酸酯与亚胺反应的催化剂时，我们以良好的收率和优异的对映选择性获得了富含对映异构体的吡咯啉。这两种非对映异构膦用作假对映异构体，提供具有相反绝对构型的手性吡咯啉。
• Catalytic Enantioselective Synthesis of Guvacine Derivatives through [4 + 2] Annulations of Imines with α-Methylallenoates
  作者：Qihai Xu、Nathan J. Dupper、Andrew J. Smaligo、Yi Chiao Fan、Lingchao Cai、Zhiming Wang、Adam D. Langenbacher、Jau-Nian Chen、Ohyun Kwon

  DOI：10.1021/acs.orglett.8b02489

  日期：2018.10.5

  These HypPhos catalysts were assembled from trans-4-hydroxyproline, with the modular nature of the synthesis allowing variations of the exocyclic P and N substituents. Among them, exo-(p-anisyl)-HypPhos was most efficacious for [4 + 2] annulations between ethyl α-methylallenoate and imines. Through this method, (R)-aplexone was identified as being responsible for the decrease in the cellular levels

  P-手性[2.2.1]双环膦（HypPhos催化剂）已应用于α-烷基联烯酸酯和亚胺之间的反应，生产鳄梨毒肽衍生物。这些 HypPhos 催化剂由反式-4-羟基脯氨酸组装而成，合成的模块化性质允许环外 P 和 N 取代基的变化。其中， exo -(对茴香基)-HypPhos 对于 α-甲基联烯酸乙酯和亚胺之间的 [4 + 2] 成环最有效。通过这种方法，( R )-aplexone 被确定为细胞胆固醇水平降低的原因。