tert-butyl benzoyl-L-prolinate

• 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: tert-butyl benzoyl-L-prolinate
• 英文别名: N-benzoyl proline tert-butyl ester；tert-butyl (2S)-1-benzoyl-2-pyrrolidinecarboxylate；tert-butyl (2S)-1-benzoylpyrrolidine-2-carboxylate
• 化学式: C₁₆H₂₁NO₃
• 分子量: 275.348
• InChiKey: JHEIRHCXJXSQIP-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl benzoyl-L-prolinate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-苯甲酰基-l-脯氨酸
  参考文献：
  名称：

  Potent, Small-Molecule Inhibitors of Human Mast Cell Tryptase. Antiasthmatic Action of a Dipeptide-Based Transition-State Analogue Containing a Benzothiazole Ketone

  摘要：

  Inhibitors of human mast cell tryptase (EC 3.4.21.59) have therapeutic potential for treating allergic or inflammatory disorders. We have investigated transition-state mimetics possessing a heterocycle-activated ketone group and identified in particular benzothiazole ketone (2S)-6 (RWJ-56423) as a potent, reversible, low-molecular-weight tryptase inhibitor with a K-i value of 10 nM. A single-crystal X-ray analysis of the sulfate salt of (2S)-6 confirmed the stereochemistry. Analogues 12 and 15-17 are also potent tryptase inhibitors. Although RWJ-56423 potently inhibits trypsin (K-i = 8.1 nM), it is selective vs other serine proteases, such as kallikrein, plasmin, and thrombin. We obtained an X-ray structure of (2S)-6 complexed with bovine trypsin (1.9-Angstrom resolution), which depicts inter alia a hemiketal involving Ser-189, and hydrogen bonds with His-57 and Gln-192. Aerosol administration of 6 (2R,2S; RWJ-58643) to allergic sheep effectively antagonized antigen-induced asthmatic responses, with 70-75% blockade of the early response and complete ablation of the late response and airway hyperresponsiveness.

  DOI：

  10.1021/jm030050p
• 作为产物：
  描述：

  L-脯氨酸叔丁酯盐酸盐 、 苯甲醇 在 叔丁基过氧化氢 、 iron(II) chloride tetrahydrate 、 calcium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 4.0h， 以55%的产率得到tert-butyl benzoyl-L-prolinate
  参考文献：
  名称：

  Iron-catalyzed benzamide formation. Application to the synthesis of moclobemide

  摘要：

  A convenient and user-friendly method to yield benzamides from primary and secondary amines and various benzylic alcohols in the presence of a cheap iron salt (FeCl2 center dot 4H(2)O) and tert-butylhydroperoxide (70% in water) as a stoichiometric oxidant is described. Control experiments indicated that this reaction might involve radical species. This method proved to be general, generating a family of 30 benzamides and was applied to the preparative synthesis of anti-anxiety drug moclobemide. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2014.06.001

文献信息

• Benzyne-Mediated Esterification Reaction
  作者：Jinlong Zhao、Jiarong Shi、Yang Li

  DOI：10.1021/acs.orglett.1c02702

  日期：2021.9.17

  A benzyne-mediated esterification of carboxylic acids and alcohols under mild conditions has been realized, which is made possible via a selective nucleophilic addition of carboxylic acid to benzyne in the presence of alcohol. After a subsequent transesterification with alcohol, the corresponding esters can be produced efficiently. This benzyne-mediated protocol can be used on the modification of Ibuprofen

  已经实现了在温和条件下苯炔介导的羧酸和醇的酯化，这可以通过在醇存在下选择性地将羧酸亲核加成到苯上来实现。随后与醇进行酯交换后，可以有效地生产相应的酯。这种苯介导的协议可用于布洛芬、胆固醇、雌二醇的修饰和苯丙酸诺龙的合成。此外，苄还可用于促进内酯化和酰胺化反应。
• UV-Light-Induced N-Acylation of Amines with α-Diketones
  作者：Zhihui Xu、Tianbao Yang、Niu Tang、Yifeng Ou、Shuang-Feng Yin、Nobuaki Kambe、Renhua Qiu

  DOI：10.1021/acs.orglett.1c01599

  日期：2021.7.16

  induced by ultraviolet (UV) light. Forty-six examples with various functional groups are explored at room temperature with irradiation by three 26 W UV lamps (350–380 nm). The yield reaches 97%. The gram scale experiment product yield is 76%. Moreover, this system can be applied to the synthesis of several amino acid derivatives. Mechanistic studies show that benzoin is generated in situ from benzil under

  在此，我们开发了一种温和的方法，用于由紫外线 (UV) 光诱导的 α-二酮对伯胺和仲胺的N-酰化。在室温下用三个 26 W 紫外线灯 (350–380 nm) 照射探索了 46 个具有不同官能团的例子。收率达到97%。克级实验产物收率为76%。此外，该系统可应用于多种氨基酸衍生物的合成。机理研究表明，安息香是在紫外线照射下由苯偶姻原位生成的。
• (9H-Fluoren-9-yl)methanesulfonyl (Fms): An Amino Protecting Group Complementary to Fmoc
  作者：Yoshitaka Ishibashi、Kengo Miyata、Masato Kitamura

  DOI：10.1002/ejoc.201000682

  日期：2010.8

  developed. The advantages of this new PG were demonstrated in the successful formation of a phosphonamide between an N-Fms-protected α-phosphonoalanine monoester and secondary alkylamines, including (R)-2-phenylethylamine, (S)-phenylalanine tert-butyl ester (H-Phe-OtBu), H-Pro-Gly-OtBu, and H-Phe-Phe-OtBu, without formation of oxazaphospholine, which is a serious problem associated with the Fmoc PG

  开发了基于磺酰胺的保护基团 (PG)，(9H-芴-9-基) 甲磺酰基 (Fms)，其使用方式与成熟的 Fmoc PG 类似。这种新型 PG 的优势在 N-Fms 保护的 α-膦酰基丙氨酸单酯和仲烷基胺（包括 (R)-2-苯乙胺、(S)-苯丙氨酸叔丁酯 (H) -Phe-OtBu)、H-Pro-Gly-OtBu 和 H-Phe-Phe-OtBu，不会形成氧氮杂膦，这是与 Fmoc PG 相关的严重问题。这一成功应该为在基本上任意位置用 α-氨基膦酸 (AP) 取代的非天然肽的固相合成铺平道路，而无需对自 Carpino 在 1970 年的报告以来积累的基于 Fmoc 的化学进行重大修改。
• Two-Chamber Aminocarbonylation of Aryl Bromides and Triflates Using Amino Acids as Nucleophiles
  作者：Jens Lindman、Anubha Yadav、Johan Gising、Mats Larhed

  DOI：10.1021/acs.joc.3c00972

  日期：2023.9.15

  A palladium(0)-catalyzed aminocarbonylation reaction employing molybdenum hexacarbonyl as a carbon monoxide precursor for the production of N-capped amino acids using aryl and heteroaryl bromides and triflates is reported. The carbon monoxide is formed ex situ through the use of a two-chamber system, where carbon monoxide generated in one chamber is free to diffuse over and be consumed in the other

  据报道，使用六羰基钼作为一氧化碳前体，使用芳基和杂芳基溴化物和三氟甲磺酸酯生产 N-封端氨基酸，钯 (0) 催化的氨基羰基化反应。一氧化碳是通过使用双室系统异位形成的，其中一个室中产生的一氧化碳可以自由扩散到另一个钯催化反应室中并被消耗。使用该方法，利用两个系列的芳基溴和芳基三氟甲磺酸酯合成了 21 个 N-封端氨基酸，分离产率在 40% 至 91% 之间。
• Deoxy-Arylation of Amides via a Tandem Hydrosilylation/Radical– Radical Coupling Sequence
  作者：Nicholas J. Venditto、Jeffrey A. Boerth

  DOI：10.1021/acs.orglett.4c01121

  日期：——

  for single electron reduction to generate α-amino radicals. Leveraging the ability to generate α-amino radicals from these hemiaminals, we describe a two-step, one-pot, deoxy-arylation of amides utilizing iridium-catalyzed hydrosilylation and photoredox catalysis. This transformation can be tailored toward the late-stage functionalization of biologically relevant molecules, with drug discovery applications

  Vaska 的配合物是酰胺氢化硅烷化的重要催化剂。在这些过程中形成的O-甲硅烷基半缩醛胺中间体已被证明是用于亲核加成的亲电子试剂。最近，这些中间体已被证明适合单电子还原生成 α-氨基自由基。利用这些半缩醛胺生成α-氨基自由基的能力，我们描述了利用铱催化的硅氢加成和光氧化还原催化的酰胺的两步、一锅脱氧芳基化。这种转变可以针对生物相关分子的后期功能化进行定制，并可用于药物发现应用，如 NPY Y2 抑制剂的简化合成所示。