(1S,3S)-methyl 1-phenyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole-3-carboxylate | 91200-21-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (1S,3S)-methyl 1-phenyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole-3-carboxylate
• 英文别名: cis-1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester；(1S,3S)-methyl 1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；(1S,3S)-methyl-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；methyl (1S,3S)-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；3-(methoxycarbonyl)-1,2,3,4-tetrahydro-9H-pyrido-[3,4-b]-indole-1-benzene；cis-1-phenyl-3-methoxycarbonyl-1,2,3,4-tetrahydro-β-carboline；cis methyl 1,2,3,4-tetrahydro-1-phenyl-9H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 91200-21-4
• 化学式: C₁₉H₁₈N₂O₂
• 分子量: 306.364
• InChiKey: PKHHJECXXHOADW-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,3S)-methyl 1-phenyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole-3-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 60.0~81.0 ℃ 、111.47 kPa 条件下， 反应 28.0h， 生成 (1S,3R)-1-phenyl-2,3,4,9-tetrahydro-1H-pyridine[3,4-b]indole-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted tetrahydro-β-carbolines into (1S,3R)-trans-1,3-disubstituted tetrahydro-β-carbolines: an improved asymmetric synthesis of tadalafil from l-tryptophan

  摘要：

  An efficient and general method for the highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted 1,2,3,4-tetrahydro-beta-carbolines (THBCs) into (15,3R)-trans-1,3-disubstituted THBCs is described. The method contains the following three steps: the enantiomerically pure (1S,3S)-cis-1,3-disubstituted THBCs 1 were first converted into (1S,3S)-cis-1,2,3-trisubstituted THBCs 2 by N-1-naphthylmethylation/benzylation; (15,3S)-cis-1,2,3-trisubstituted THBCs 2 were then converted into (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 in high yields and with high stereoselectivities via a base-catalyzed epimerization at C-3; (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 were subsequently converted into (15,3R)-trans-1,3-disubstituted THBCs 4 after reductive removal of the 1-naphthylmethyl/benzyl group. In addition, as an application of this method, an improved and highly stereoselective synthesis of the PDE5 inhibitor tadalafil (Cialis (R)) starting from natural and less expensive L-tryptophan was developed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.06.006
• 作为产物：
  描述：

  L-色氨酸甲酯 在 三氟乙酸 、 原甲酸三甲酯 作用下， 以 二氯甲烷 为溶剂， 反应 26.5h， 生成 (1S,3S)-methyl 1-phenyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole-3-carboxylate
  参考文献：
  名称：

  Synthesis and Evaluation of Tryprostatin B and Demethoxyfumitremorgin C Analogues

  摘要：

  Tryprostatin B and demethoxyfumitremorgin C are fungal inhibitors of mammalian cell cycle progression at the G(2)/M transition. N-Alkyl derivatives of the L-TrP-L-Pro diketopiperazine were prepared as analogues of tryprostatin B, and two of these were more active than the natural product. A second series of cis- and trans-tetrahydro-beta-carbolines annulated to a diketopiperazine were prepared as analogues of demethoxyfumitremorgin C. The nature of the alkyl substituent, as well as its cis or trans relationship in the tetrahydro-beta-carboline ring, was found to have a significant effect on cytotoxic activity. Small cis-alkyl substituents fall into the demethoxyfumitremorgin C family, whereas bulky benzyl trans compounds appear to act via a different mechanism of action.

  DOI：

  10.1021/jm9905662

文献信息

• Exploration of TRPM8 Binding Sites by β-Carboline-Based Antagonists and Their In Vitro Characterization and In Vivo Analgesic Activities
  作者：Alessia Bertamino、Carmine Ostacolo、Alicia Medina、Veronica Di Sarno、Gianluigi Lauro、Tania Ciaglia、Vincenzo Vestuto、Giacomo Pepe、Manuela Giovanna Basilicata、Simona Musella、Gerardina Smaldone、Claudia Cristiano、Sara Gonzalez-Rodriguez、Asia Fernandez-Carvajal、Giuseppe Bifulco、Pietro Campiglia、Isabel Gomez-Monterrey、Roberto Russo

  DOI：10.1021/acs.jmedchem.0c00816

  日期：2020.9.10

  Transient receptor potential melastatin 8 (TRPM8) ion channel represents a valuable pharmacological option for several therapeutic areas. Here, a series of conformationally restricted derivatives of the previously described TRPM8 antagonist N,N′-dibenzyl tryptophan 4 were prepared and characterized in vitro by Ca2+-imaging and patch-clamp electrophysiology assays. Molecular modeling studies led to

  瞬时受体电位褪黑素8（TRPM8）离子通道代表了几个治疗领域的宝贵药理学选择。在此，制备了先前描述的TRPM8拮抗剂N，N′-二苄基色氨酸4的一系列构象受限的衍生物，并通过Ca 2+成像和膜片钳电生理测定体外表征。分子建模研究导致在TRPM8结合位点内确定了这些衍生物的广泛且明确定义的相互作用网络，这是其拮抗剂活性的基础。（5 R，11a S）-5-（4-氯苯基）-2-（4-氟苄基）-5,6,11,11a-四氢-1 H-咪唑[1'，5'：1,6]吡啶[3,4-b ]吲哚-1,3（2 H）-二酮（31a）以有效的（IC 50 = 4.10±1.2 nM），选择性且代谢稳定的TRPM8拮抗剂出现。在体内，31a在icilin诱导的WDS（11.5 mg / kg ip），奥沙利铂诱导的冷异常性疼痛（10-30μgsc）和CCI诱导的热痛觉过敏（11.5 mg / kg）中显示出显着的靶标覆盖范围。
• Highly diastereoselective crystallization-induced asymmetric transformation of 1,3-disubstituted-tetrahydro-β-carbolines in water
  作者：Tian-Zhuo Meng、Xiao-Xin Shi、Hui-Ya Qu、Yi Zhang、Zhong-Shou Huang、Qi-Qi Fan

  DOI：10.1039/c7ra08811f

  日期：——

  A green and highly stereoselective method for the synthesis of cis or trans-1,3-disubstituted-tetrahydro-β-carbolines has been developed using water as the solvent. A mixture of cis and trans-1,3-disubstituted-tetrahydro-β-carboline hydrochlorides can be converted to a single cis or trans isomer via a crystallization-induced asymmetric transformation process. It is possible to get both isomers using

  已经开发出一种以水为溶剂合成顺式或反式-1,3-二取代-四氢-β-咔啉的绿色且高度立体选择性的方法。顺式和反式-1,3-二取代-四氢-β-咔啉盐酸盐的混合物可以通过结晶诱导的不对称转化过程转化为单一的顺式或反式异构体。通过在水中加入不同的添加剂，可以使用这种方法获得两种异构体。该方法具有环境友好，立体选择性高，适合工业化和无毒等优点。
• Biological Studies and Target Engagement of the 2-<i>C</i>-Methyl-<scp>d</scp>-Erythritol 4-Phosphate Cytidylyltransferase (IspD)-Targeting Antimalarial Agent (1<i>R</i>,3<i>S</i>)-MMV008138 and Analogs
  作者：Maryam Ghavami、Emilio F. Merino、Zhong-Ke Yao、Rubayet Elahi、Morgan E. Simpson、Maria L. Fernández-Murga、Joshua H. Butler、Michael A. Casasanta、Priscilla M. Krai、Maxim M. Totrov、Daniel J. Slade、Paul R. Carlier、Maria Belen Cassera

  DOI：10.1021/acsinfecdis.7b00159

  日期：2018.4.13

  to gain insight into the structure–activity relationships by probing the ability of MMV008138 analogs to inhibit PfIspD recombinant enzyme. Here, we report PfIspD inhibition data for fosmidomycin (FOS) and 19 previously disclosed analogs and report parasite growth and PfIspD inhibition data for 27 new analogs of MMV008138. In addition, we show that MMV008138 does not target the recently characterized

  疟疾仍然是世界上最致命的疾病之一，耐药性寄生虫的出现一直是威胁。疟原虫寄生虫利用甲基赤藓糖醇磷酸酯（MEP）途径来合成异戊烯基焦磷酸酯（IPP）和二甲基烯丙基焦磷酸酯（DMAPP），这对于寄生虫的生长至关重要。以前，我们和其他人发现，疟疾框化合物MMV008138靶向于原生质体，并且该化合物对寄生虫的生长抑制作用可以通过补充IPP来逆转。进一步的工作表明，MMV008138靶向2- C-甲基-d酶。MEP途径中的-赤藓糖醇4-磷酸胞苷转移酶（ISPD），可将MEP和胞苷三磷酸（CTP）转化为胞苷二磷酸甲基赤藓糖醇（CDP-ME）和焦磷酸。在这项工作中，我们试图通过探索MMV008138类似物抑制Pf ISPD重组酶的能力来深入了解结构与活性之间的关系。这里，我们报告Pf的ISPD抑制数据用于膦胺霉素（FOS）和19个以前公开的类似物和报告寄生虫生长和Pf的ISPD抑制数据用于MMV0081
• A new method for the preparation of 3,4-dihydro - and 1,2,3,4-tetrahydro-.BETA.-carbolines.
  作者：AKIHIKO ISHIDA、TOHRU NAKAMURA、KUNIHIKO IRIE、TOKURO OHISHI

  DOI：10.1248/cpb.33.3237

  日期：——

  N-Alkylthiocarbonyltryptophan (2a-i) and tryptamine (2j-m) derivatives can be converted into the corresponding 3, 4-dihydro-β-carbolines (3) under mild conditions by the use of alkylating or acylating agents. The NaBH4 reduction of 1, 3-disubstituted 3, 4-dihydro-β-carbolines (3a-i) gave cis- (5) or trans-1, 2, 3, 4-tetrahydro-β-carbolines (6) with satisfactory stereoselectivity. The synthesis of optically active 3a, b and 5a, b is also described.

  N-烷基硫羰基色氨酸（2a-i）和色氨酸（2j-m）衍生物可以在温和条件下通过烷基化或酰基化剂转化为相应的3, 4-二氢-β-氨基吲哚（3）。1, 3-二取代的3, 4-二氢-β-氨基吲哚（3a-i）经过NaBH4还原，得到了具有满意立体选择性的顺式（5）或反式-1, 2, 3, 4-四氢-β-氨基吲哚（6）。本文还描述了外消旋活性3a, b和5a, b的合成。
• <i>Cis</i>-Diastereoselectivity in Pictet-Spengler Reactions of<scp>L</scp>-Tryptophan and Electronic Circular Dichroism Studies
  作者：Naghmana Rashid、Samina Alam、Mashooda Hasan、Naeema Khan、Khalid M. Khan、Helmut Duddeck、Gennaro Pescitelli、Ágnes Kenéz、Sándor Antus、Tibor Kurtán

  DOI：10.1002/chir.22070

  日期：2012.10

  The diastereoselective synthesis of optically active 1,3‐disubstituted tetrahydro‐β‐carbolines using polar protic Pictet–Spengler cyclization of (S)‐tryptophan methyl ester with five aldehydes RCHO (R═CH3, C2H5, C3H7, C4H9, and C6H5) was studied. As an alternate route, the cyclization of (S)‐tryptophan with the same aldehydes and subsequent methylation of the resulting tetrahydro‐β‐carboline carboxylic

  光学活性的1,3-二取代使用（的极性质子的Pictet Spengler环化生成四氢β咔啉的非对映选择性合成小号） -色氨酸甲酯五醛RCHO（R = CH 3，C 2 H ^ 5，C 3 H ^ 7，C 4 H 9和C 6 H 5）进行了研究。作为替代方法，还进行了将（S）-色氨酸与相同的醛环化，然后将所得的四氢-β-咔啉羧酸进行甲基化的比较。13C NMR和电子圆二色性（ECD）研究以及随时间变化的密度泛函理论ECD计算数据确定了合成化合物的相对1,3顺式/反式和绝对构型（1 S，3 S / 1 R，3 S） 。对制备的化合物进行的固态和溶液ECD研究，得到ECD计算和X射线数据的支持，为1,3-二取代四氢-β-咔啉的构型分配提供了可靠的ECD方法，并揭示了决定化学反应的立体化学因素。典型的ECD数据。手性24：789–795，2012。分级为4 +©2012 Wiley Periodicals，Inc