2-(benzhydrylideneamino)-1-(10,10-dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1.5]dec-4-yl)ethanone | 138566-17-3

• 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: 2-(benzhydrylideneamino)-1-(10,10-dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1.5]dec-4-yl)ethanone
• 英文别名: 1-((6R,7aR)-8,8-dimethyl-2,2-dioxidotetrahydro-3H-3a,6-methanobenzo[c]isothiazol-1(4H)-yl)-2-((diphenylmethylene)amino)ethan-1-one；2-(benzhydrylideneamino)-1-[(1S,5R,7R)-10,10-dimethyl-3,3-dioxo-3λ6-thia-4-azatricyclo[5.2.1.01,5]decan-4-yl]ethanone
• CAS: 138566-17-3
• 化学式: C₂₅H₂₈N₂O₃S
• 分子量: 436.575
• InChiKey: GWFWLGONUVZQPT-DNRQZRRGSA-N

物化性质

• 沸点：
  555.8±56.0 °C(Predicted)
• 密度：
  1.30

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  75.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(benzhydrylideneamino)-1-(10,10-dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1.5]dec-4-yl)ethanone 在 盐酸 、 六甲基磷酰三胺 、 正丁基锂 、 silica gel 作用下， 以 氯仿 为溶剂， 反应 2.0h， 生成 L-3,3-diphenylalaninesultam hydrochloride
  参考文献：
  名称：

  Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor

  摘要：

  Constrained analogues of phenylalanine have been conceptually designed for analyzing the binding pockets of Phe(7) (S-7) and Phe(8) (S-8), two aromatic residues important for the pharmacological properties of SP, i.e., L-tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2-indanylglycine, the diastereomers of L-1-indanylglycine (Ing) and L-1-benz[f]indanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine (Delta(z)Phe, Delta(E)Phe). Binding studies were performed with appropriate ligands and tissue preparations allowing the discrimination of the three tachykinin binding sites, NK-1, NK-2, and NK-3. The potencies of these agonists were evaluated in the guinea pig ileum bioassay. According to the binding data, we can conclude that the S-7 subsite is small, only the gauche (-) probe [(2S,3S)-Ing(7)]SP presents a high affinity for specific NK-1 binding sites. Surprisingly, the [Delta(E)Phe(7)]SP analogue, which projects the aromatic ring toward the trans orientation, is over 40-fold more potent than the Z isomer, [Delta(Z)Phe(7)]SP. A plausible explanation of these conflictual results Is that either the binding protein quenches the minor trans rotamer of [(2S,3S)-Ing(7)]SP in solution or this constrained amino acid side chain rotates when inserted in the protein. In position 8, the high binding affinities of [Flg(8)]SP and [(2S,3S)-Bfi(8)]SP suggest that the S-8 subsite is large enough to accept two aromatic rings in the gauche (-) and one aromatic ring in the trans direction. Peptides bearing two conformational probes in positions 7, 8, or 9 led to postulate that S-7, S-8, and S-9 subsites are independent from each other. The volumes available for side chains 7 and 8 can be estimated to be close to 110 and 240 Angstrom(3), respectively. The large volume of the S-8 subsite raises question on the localization of the SP-binding site in the NK-1 receptor. If SP were to bind in the transmembrane domains, the cleft defined by the seven transmembrane segments must rearrange during the binding process in order to bind a peptide in an ac-helical structure and at least one large binding subsite in position 8. Thus, indirect topographical analysis with constrained amino acids might contribute to the analysis of the receptor/ligand dynamics. Finally, this study demonstrates that a good knowledge of the peptidic backbone structure and a combination of constrained amino acids are prerequisites to confidently attribute the preferred orientation(s) of an amino acid side chain.

  DOI：

  10.1021/jm00037a009
• 作为产物：
  描述：

  二苯亚甲基甘氨酸甲酯 、 (2R)-bornane-10,2-sultam 在 三甲基铝 作用下， 生成 2-(benzhydrylideneamino)-1-(10,10-dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1.5]dec-4-yl)ethanone
  参考文献：
  名称：

  Asymmetric synthesis of L-diphenylalanine and L-9-fluorenylglycine via room temperature alkylations of a sultam-derived glycine imine

  摘要：

  L-diphenylalanine and L-9-fluorenylglycine were prepared from a sultam-derivated glycine imine 3 via room temperature-asymmetric-alkylation/ hydrolysis/mild-sultam-clivage. The L-configuration was ascertained using an X-ray analysis of the alkylation product 4b.

  DOI：

  10.1016/0040-4039(91)80217-t

文献信息

• A convenient and highly enantioselective synthesis of (<i>S</i>)-2-pipecolic acid: an efficient access to caine anesthetics
  作者：Yuyan Yang、Hua Li、Zhonglin You、Xingxian Zhang

  DOI：10.1080/00397911.2021.1961155

  日期：2021.10.18

  Abstract A novel and enantioselective synthesis of (S)-2-pipecolic acid (5) has been achieved from Oppolzer’s sultam (1) and ethyl N-(diphenylmethylene)glycinate (2) as readily available starting materials. The highly stereoselective alkylation of chiral glycine intermediate (3) with 1,4-dibromobutane afforded the key backbone of (S)-2-pipecolic acid (5) in one-step that was utilized into the preparation

  摘要 已经从 Oppolzer 的 sultam ( 1 ) 和N- (二苯基亚甲基) 甘氨酸乙酯 ( 2 ) 作为容易获得的起始材料实现了 ( S )-2-哌啶酸 ( 5 )的新型和对映选择性合成。手性甘氨酸中间体 ( 3 ) 与 1,4-二溴丁烷高度立体选择性烷基化，一步得到 (S)-2-哌啶酸 ( 5 )的关键骨架，用于制备局部麻醉剂甲哌卡因、罗哌卡因和布比卡因。
• An Efficient and Highly Asymmetric Synthesis of (<i>S</i>)-2’,6’-Dimethyltyrosine
  作者：Kailun He、Fangmeng Zhu、Hua Li、Jian Tang、Xingxian Zhang

  DOI：10.1080/00304948.2020.1798729

  日期：2020.11.1

  The unnatural amino acid (S)-2,6-dimethyltyrosine [(S)-DMT, Figure 1] is a very important small molecule for the preparation of opioid receptor modulators. It has been used to effectively improve t...

  非天然氨基酸 (S)-2,6-二甲基酪氨酸 [(S)-DMT，图 1] 是用于制备阿片受体调节剂的非常重要的小分子。它已被用来有效地提高...
• A New Convergent Approach to Biphenomycin Antibiotics
  作者：Franz F. Paintner、Klaus Görler、Wolfgang Voelter

  DOI：10.1055/s-2003-37506

  日期：——

  A new, convergent approach to the biaryl key intermediate of Schmidt’s biphenomycin B total synthesis has been accomplished via a palladacycle complex catalyzed Stille cross-coupling of two o-tyrosine building blocks.

  Schmidt 的联苯霉素 B 全合成的联芳基关键中间体的一种新的收敛方法已通过钯环复合物催化的两个邻酪氨酸结构单元的 Stille 交叉偶联实现。
• 一种(S)-2-哌啶甲酸的制备方法
  申请人：浙江工业大学

  公开号：CN111995565B

  公开（公告）日：2022-01-25

  一种(S)‑2‑哌啶甲酸的制备方法：在路易斯酸催化下，L‑樟脑磺酰胺(I)与二苯基亚胺酯(II)发生缩合反应，生成化合物(III)；化合物(III)与化合物(IV)经强碱作用下的不对称烷基化、酸性条件下的亚胺水解、分子内环合“一锅法”制得化合物(V)；化合物(V)在碱性条件下脱去手性辅助基，得到目标化合物(S)‑2‑哌啶甲酸(TM)；本发明方法总共经过三步就可以得到目标产物，该法具有原料价廉易得、路线简短、收率高、立体选择性好等优点，目前(S)‑2‑哌啶甲酸为诸多药物的重要手性中间体，具有良好的市场前景；
• Synthesis and 19F NMR parameters of a perfluoro-tert-butoxy tagged L-DOPA analogue
  作者：Simonetta Orlandi、Marco Cavazzini、Silvia Capuani、Andrea Ciardello、Gianluca Pozzi

  DOI：10.1016/j.jfluchem.2020.109596

  日期：2020.9

  The robust multistep synthesis of a perfluoro-tert-butoxy (PFTB) tagged analogue of the non-proteinogenic amino acid 3,4-dihydroxy-L-phenylalanine (L-DOPA) via diastereoselective benzylation of Oppolzer’s sultam glycinate was developed. The new compound is characterized by a flexible alkoxy linker connecting PFTB to the biochemically and pharmacologically relevant L-DOPA scaffold, which facilitates

  开发了通过Oppolzer的苏丹草甘氨酸盐酸盐的非对映选择性苄基化方法，对非蛋白原氨基酸3,4-二羟基-L-苯丙氨酸（L-DOPA）进行全氟叔丁氧基（PFTB）标记的类似物的稳健多步合成。新化合物的特征是将PFTB连接到生物化学和药理学相关的L-DOPA支架的柔性烷氧基接头，该支架促进了氟化部分的自由运动。因此，这9个化学当量的氟原子产生了强烈而尖锐的19 F NMR单线态信号，该信号在水性环境中容易检测到。此外，血液溶液中19 F NMR弛豫过程的动力学符合将新化合物潜在用作探针的要求。19 F磁共振成像在翻译临床领域中的应用。