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“Build Your Own” ADC Mimics: Identification of Nontoxic Linker/Payload Mimics for HIC-Based DAR Determination, High-Throughput Optimization, and Continuous Flow Conjugation "自制 "ADC 模拟物:为基于 HIC 的 DAR 确定、高通量优化和连续流共轭鉴定无毒连接体/负载模拟物
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-17 DOI: 10.1021/acs.oprd.4c00226
Marion H. Emmert, Cecilia Bottecchia, Rodell C. Barrientos, Yinnian Feng, Daniel Holland-Moritz, Gregory J. Hughes, Yu-Hong Lam, Erik L. Regalado, Serge Ruccolo, Shuwen Sun, Rebecca Chmielowski, Cuixian Yang, François Lévesque, Kelly Raymond, Monica Haley
This manuscript reports the identification of hydrophobic interaction chromatography (HIC)-shifting, nontoxic linker-payload surrogates as tool molecules for the optimization of maleimide/cysteine conjugations relevant to antibody–drug conjugates (ADCs). These linker/payload (LP) mimics allow conjugation measurement via HIC with mAbs (monoclonal antibodies) bearing engineered or interchain cysteines as conjugation sites. Importantly, the tool molecules are employed to optimize maleimide/cysteine conjugations via modern methods of process development, including high-throughput experimentation and continuous flow. Overall, our studies provide confidence that commercially available, nontoxic LP mimics can be employed successfully to optimize ADC-type conjugations in batch and flow while minimizing materials needs and experimental work in specialized facilities required for potent compound handling.
本手稿报告了疏水相互作用色谱(HIC)转换、无毒性连接体-负载替代物的鉴定结果,作为优化马来酰亚胺/半胱氨酸共轭抗体-药物共轭物(ADC)的工具分子。这些连接体/载荷(LP)模拟物可以通过 HIC 与以工程半胱氨酸或链间半胱氨酸为连接位点的 mAbs(单克隆抗体)进行连接测量。重要的是,这些工具分子可用于通过现代工艺开发方法(包括高通量实验和连续流)优化马来酰亚胺/半胱氨酸共轭。总之,我们的研究让人相信,市面上无毒的 LP 模拟物可以成功地用于批量和流程中 ADC 型共轭物的优化,同时最大限度地减少材料需求和强效化合物处理所需的专业设施中的实验工作。
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引用次数: 0
Scalable Synthesis of ABBV-105 Enabled by Suzuki Coupling with Low Pd Loading, Ru-Catalyzed Asymmetric Hydrogenation, and Acylation Using Impinging Jet 利用低钯载荷的铃木偶联、Ru 催化的不对称氢化反应和撞击喷射的酰化反应实现 ABBV-105 的可扩展合成
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-17 DOI: 10.1021/acs.oprd.4c00117
Benoit Cardinal-David, Shashank Shekhar, Eric M. Phillips, Elizabeth C. Swift, Brian Kotecki, Andrew R. Ickes, Gregory E. Storer, Daniel D. Caspi, Anuj Verma, Eric G. Moschetta, Daniel Tao, Westin H. Morrill, John R. Bellettini, Fredrik L. Nordstrom, Alessandra Mattei, Kirsten Springer, Haixiao Qiu, Jeffrey T. Bien, Onkar Manjrekar, Rodger F. Henry, Grier A. Wallace, Lisa Schaffter, Eric A. Voight
Evolution of a synthetic process to prepare ABBV-105, a Bruton’s tyrosine kinase (BTK)-inhibitor, on multikilogram scale is described. The first-generation route utilized chiral resolution of the penultimate intermediate (7). Either Bartoli or Leimgruber–Batcho indole synthesis was used to prepare the key intermediate, indole boronate ester (23). As the demand for the API increased, the first-generation route was found to be low-yielding and expensive. It required column chromatography, had multiple alerting structures from the mutagenic impurity assessment, and suffered from lack of robustness. In the second-generation route a novel Ru-catalyzed asymmetric hydrogenation of 1,2,5,6-tetrahydropyridine (21) was developed to establish the stereocenter. Compound 21 was accessed via Suzuki coupling of 23, prepared by Friedel–Crafts acylation, with vinyl bromide (24) in the presence of very low loading of a Pd catalyst (0.15 mol % Pd). Finally, the penultimate intermediate (7) was coupled with acryloyl chloride using an impinging jet to prepare the API. Detailed kinetic and mechanistic work was conducted to control the persistent impurities formed in the API step. The second-generation route was robust, chromatography-free and high-yielding with low mutagenic liability.
本文介绍了制备多千克规模的布鲁顿酪氨酸激酶(BTK)抑制剂 ABBV-105 的合成工艺的演变过程。第一代路线利用倒数第二个中间体的手性解析 (7)。巴托利或莱姆格鲁伯-巴乔吲哚合成法用于制备关键中间体吲哚硼酸酯(23)。随着对原料药需求的增加,人们发现第一代路线产量低、成本高。这种方法需要柱层析,在致突变杂质评估中存在多种警示结构,而且缺乏稳健性。在第二代路线中,开发了一种新型 Ru 催化的 1,2,5,6- 四氢吡啶 (21) 不对称氢化反应,以建立立体中心。化合物 21 是通过弗里德尔-卡夫斯酰化法制备的 23 与溴化乙烯基 (24) 在极低的钯催化剂负载量(0.15 摩尔% 钯)下进行铃木偶联而得到的。最后,倒数第二种中间体(7)与丙烯酰氯通过撞击喷射结合,制备出原料药。为控制原料药步骤中形成的持久性杂质,进行了详细的动力学和机械学研究。第二代工艺路线稳健、无需色谱、产量高且诱变性低。
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引用次数: 0
THETA as an Efficient Cu-Binding Ligand for Manual and Automated “Click” Synthesis: the Rufinamide Case THETA 作为手动和自动 "点击 "合成的高效铜结合配体:鲁菲那胺案例
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-15 DOI: 10.1021/acs.oprd.4c00129
Aleksander Szkółka, Przemysław W. Szafrański, Patryk Kasza, Przemysław Talik, Mirosław Krośniak, Marek Cegła, Paweł Zajdel
Rufinamide {1-[(2,6-difluorophenyl)methyl]-1H-1,2,3-triazole-4-carboxamide} was the first anticonvulsant agent used in the treatment of Lennox–Gastaut syndrome─a rare, complex, and severe childhood-onset epilepsy. It is synthesized by thermal azide–alkyne cycloaddition, which can produce some of the unwanted 1,5-disubstituted triazole byproduct. To address this issue, copper-catalyzed azide–alkyne cycloaddition (CuAAC) methods have been proposed. In this context, we present efficient CuAAC protocols for the synthesis of rufinamide and its precursor, methyl 1-[(2,6-difluorophenyl)methyl]-1H-1,2,3-triazole-4-carboxylate, using triazole Cu-chelating ligands as assisting additives for the CuAAC reactions. We compared the efficacy of tristriazole and monotriazole ligands in milligram-scale screening reactions. Among the more favorable tristriazoles, we chose tris{1-[(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl]methyl}amine (THETA), as an alternative to the THPTA ligand, to develop 0.5 g preparative-scale manual ligand-assisted CuAAC procedures for rufinamide (87–96% with 0.5–2 mol % Cu), and its precursor (96% with 1 mol % Cu). Finally, we demonstrated the easy transfer of this protocol to an automated two-step one-pot process, employing the ChemPU synthesis platform, to obtain rufinamide precursor in quantitative yield (2 mol % Cu loading).
鲁非那胺{1-[(2,6-二氟苯基)甲基]-1H-1,2,3-三唑-4-甲酰胺}是第一种用于治疗伦诺克斯-加斯托特综合征(一种罕见、复杂和严重的儿童期癫痫)的抗惊厥药物。它是通过热叠氮-炔环加成法合成的,这种方法会产生一些不需要的 1,5-二取代三唑副产物。为解决这一问题,有人提出了铜催化叠氮-炔环加成(CuAAC)方法。在此背景下,我们采用三唑铜螯合配体作为 CuAAC 反应的辅助添加剂,提出了合成鲁菲酰胺及其前体 1-[(2,6-二氟苯基)甲基]-1H-1,2,3-三唑-4-羧酸甲酯的高效 CuAAC 方案。我们比较了三唑和单三唑配体在毫克级筛选反应中的功效。在比较有利的三苯并三唑中,我们选择了三{1-[(2-羟乙基)-1H-1,2,3-三唑-4-基]甲基}胺(THETA)作为 THPTA 配体的替代品,开发出 0.5 克制备规模的手动配体辅助 CuAAC 程序,用于生产鲁非那胺(87-96%,含 0.5-2 摩尔 % Cu)及其前体(96%,含 1 摩尔 % Cu)。最后,我们演示了如何利用 ChemPU 合成平台,将这一方案轻松转移到自动化的两步单锅流程中,从而定量(2 摩尔% Cu 加载)获得鲁菲酰胺前体。
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引用次数: 0
Process Development of Bersacapavir, Part 1: Route Scouting Effort toward a Key Amide Intermediate Bersacapavir 的工艺开发,第 1 部分:针对关键酰胺中间体的路线考察工作
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-15 DOI: 10.1021/acs.oprd.4c00153
Florian Medina, William M. Maton, Johan Weerts, Magnus Eriksson, Jean-Pierre Bongartz, Kurt Clemens, David Kossler, Micha Peeters, Koen Wegsteen, Tor Maes, Els Keppens
In this article, the route scouting effort toward a key secondary amide intermediate in the synthesis of bersacapavir is described. This study relies on the haloform reaction and the reactivity of trichloromethylketone. First, a more classical synthesis route was developed, based on the preparation of a carboxylic acid from the corresponding trichloromethylketone (conventional haloform reaction). The second, and preferred, approach utilized an innovative extension of the haloform reaction, allowing direct coupling between electron-poor aniline and trichloromethylketone. The desired amide intermediate was obtained in high yield and purity via a simple two-step synthesis using cheap and readily available starting materials.
本文介绍了合成伯沙那韦的关键仲酰胺中间体的路线探索工作。这项研究依赖于卤代烃反应和三氯甲基酮的反应性。首先,开发了一种更经典的合成路线,即从相应的三氯甲基酮制备羧酸(传统的卤代烃反应)。第二种方法,也是首选的方法,是对卤代烃反应进行创新性扩展,使贫电子苯胺与三氯甲基酮直接偶联。利用廉价易得的起始材料,通过简单的两步合成法,就能以高产率和高纯度获得所需的酰胺中间体。
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引用次数: 0
Oxygen-, Nitrogen-, and Sulfur-Containing Heterocycles: Recent Advances in De Novo Synthesis and Prospect 含氧、氮和硫的杂环:新合成的最新进展与展望
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-13 DOI: 10.1021/acs.oprd.4c00186
Yongpeng Zheng, Jianxiao Li, Wanqing Wu, Chaorong Qi, Huanfeng Jiang
Oxygen-, nitrogen-, and sulfur-containing heterocycles exhibit remarkable biological and pharmaceutical activities that are often found in naturally occurring products, pharmaceutical molecules, and synthetic compounds. Therefore, the synthesis of heterocycle building blocks has gained huge attention in the past decade. Compared with the modification of heterocyclic compounds, the construction of heterocyclic compounds from scratch is more attractive. In this Perspective, we describe our recent advances in the rational design and strategic application of the de novo synthesis of various synthetically and biologically important heterocycles. The organization of the Perspective is categorized in the following order: (a) type of heterocycle, (b) ring size of heterocycle, (c) number of heteroatoms, and (d) fused heterocycles. Moreover, some significant and representative synthetic methodologies and their synthetic applications and brief reaction mechanisms have also been described. We hope that this Perspective will help to provide a guideline for researchers who are interested in this fertile area.
含氧、氮和硫的杂环具有显著的生物和医药活性,经常出现在天然产物、医药分子和合成化合物中。因此,近十年来,杂环构件的合成受到了极大的关注。与杂环化合物的修饰相比,从头构建杂环化合物更具吸引力。在本《视角》中,我们将介绍从头合成各种具有重要合成和生物学意义的杂环的合理设计和战略应用方面的最新进展。本视角按以下顺序编排:(a) 杂环的类型,(b) 杂环的环尺寸,(c) 杂原子数,以及 (d) 融合杂环。此外,还介绍了一些重要和有代表性的合成方法及其合成应用和简要反应机理。我们希望本《视角》能为对这一肥沃领域感兴趣的研究人员提供指导。
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引用次数: 0
Stereoselective Synthesis of ABBV-992 Enabled by a Flow Diazotization and a Partial Reduction of a Pyridone 通过流式重氮化和吡啶酮的部分还原实现 ABBV-992 的立体选择性合成
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-12 DOI: 10.1021/acs.oprd.4c00077
Patrick B. Brady, Kaid C. Harper, Bryan K. Sorensen, Stephen N. Greszler, Chunqiu Lai, Alan S. Florjancic, Gang Zhao, Bhadra H. Shelat, Gregory E. Storer, Rodger F. Henry, T. Matthew Hansen
Bruton’s tyrosine kinase (BTK) is involved in B-cell receptor signaling and has been clinically validated as a target by small molecule inhibition for the treatment of a variety of cancers. ABBV-992 (1) was identified as a novel, potent, selective BTK inhibitor and advanced to Phase I clinical trials. An enantioselective synthesis of 1 was developed and scaled to provide 63 g for preclinical characterization. The route features a diazotization enabled by flow chemistry, a novel, selective partial reduction of a pyridone, a stereoselective Ellman imine reduction, and an improved acrylamide formation using 3-chloropropionyl chloride in a masked acrylate strategy.
布鲁顿酪氨酸激酶(BTK)参与 B 细胞受体信号传导,已被临床验证为治疗多种癌症的小分子抑制剂靶点。ABBV-992 (1) 是一种新型、强效、选择性 BTK 抑制剂,已进入 I 期临床试验阶段。我们开发了 1 的对映体选择性合成方法,并将其放大到 63 克,用于临床前表征。该路线的特点是通过流动化学进行重氮化,对吡啶酮进行新颖、选择性的部分还原,立体选择性的埃尔曼亚胺还原,以及在掩蔽丙烯酸酯策略中使用 3-氯丙酰氯改进丙烯酰胺的形成。
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引用次数: 0
Autonomous Online Optimization in Flash Chemistry Using Online Mass Spectrometry 利用在线质谱仪实现闪蒸化学的自主在线优化
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-12 DOI: 10.1021/acs.oprd.3c00397
Claudio Lehmann, Kevin Eckey, Maria Viehoff, Christoph Greve, Thorsten Röder
The goal of sustainable and efficient chemical production has led to an increased focus on continuous processes, especially in the production of fine chemicals or active pharmaceutical ingredients. However, developing and optimizing continuous processes can be challenging. Autonomous online optimization can help facilitate this process. This article presents a fully automated flow chemistry platform for optimizing flash chemistry (reaction times less than 1 s), using online mass spectrometry and global optimization algorithms, such as Bayesian optimization and SNOBFIT, for autonomous online optimization of chemical reactions. The algorithms were tuned and statistically evaluated using simulated optimization runs. Subsequently, they were applied in a practical case study, using a mixing-sensitive example of flash chemistry as a model system to investigate online reaction optimization. Automated response factor fitting was used to obtain quantitative data directly during reaction monitoring. This approach allowed the extraction of meaningful data without the need for postprocessing. The use of an initial design of experiments (DoE) approach was advantageous as it provides a well-discovered experimental space and often leads to a minimal number of subsequent experiments for optimization. Although random starting points may require fewer total experiments, the DoE approach offers greater reliability in achieving optimal results. Comparative analysis between Bayesian optimization and SNOBFIT indicates that Bayesian optimization outperforms SNOBFIT, achieving better results with fewer experimental iterations. Thus, Bayesian optimization has proven to be a powerful tool for autonomous optimization of chemical processes.
可持续高效化工生产的目标促使人们越来越重视连续工艺,尤其是在精细化学品或活性药物成分的生产中。然而,开发和优化连续工艺可能具有挑战性。自主在线优化有助于推动这一进程。本文介绍了一种用于优化闪速化学反应(反应时间小于 1 秒)的全自动流动化学平台,该平台使用在线质谱分析和全局优化算法(如贝叶斯优化和 SNOBFIT)对化学反应进行自主在线优化。通过模拟优化运行对算法进行了调整和统计评估。随后,将这些算法应用到实际案例研究中,以混合敏感的闪蒸化学为例,研究在线反应优化。自动反应因子拟合用于在反应监测过程中直接获取定量数据。这种方法可以提取有意义的数据,而无需进行后处理。使用初始实验设计(DoE)方法非常有利,因为它提供了一个发现良好的实验空间,而且通常只需进行最少的后续优化实验。虽然随机起点可能需要较少的实验总数,但 DoE 方法在获得最佳结果方面提供了更大的可靠性。贝叶斯优化与 SNOBFIT 的比较分析表明,贝叶斯优化优于 SNOBFIT,能以更少的实验迭代获得更好的结果。因此,贝叶斯优化法已被证明是自主优化化学过程的有力工具。
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引用次数: 0
Efficiency and Sustainability through Development of a Next-Generation, Commercial Synthesis of Valbenazine Ditosylate 通过开发新一代商业化缬氨嗪二对甲苯磺酸盐合成技术实现效率和可持续性
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-12 DOI: 10.1021/acs.oprd.4c00148
John L. Tucker, David J. Kucera, Don Hettinger, Shawn Branum, Brian Cochran, Jeff Culhane, Lucy Zhao, Andrew Benjamin Palmer, Kyle Leeman, Stanley Yu, Bénédicte Martin, Nicolas André, Julien Perron, Horacio Comas, Yuxin Zhao
The synthetic process used to manufacture valbenazine ditosylate (API of INGREZZA) has proven to be highly selective and robust, but opportunities remain for greener chemistry performance and continuous improvement enabled via simplification of process operations by truncating the manufacturing time and by reducing the overall process waste and environmental footprint during the first three most critical transformations. Neurocrine’s next-generation commercial process was developed encompassing principles of Pharmaceutical Green Chemistry ( Org. Process Res. Dev. 2006, 10, 315−319) and employs strategies for accelerated reaction kinetics, simplified reaction medium, and elimination of unnecessary workup procedures for greater process efficiency and operational agility. The new, greener process has delivered greater efficiency and sustainability by reducing the time of manufacture by 43% and reducing material use by 45% while concomitantly improving the overall process yield by 5% and reducing water use by 32%.
用于生产戊苯嗪二对甲苯磺酸盐(INGREZZA 的原料药)的合成工艺已被证明具有高度的选择性和稳健性,但在前三个最关键的转化过程中,通过缩短生产时间、减少整体工艺废物和环境足迹来简化工艺操作,仍有机会实现更环保的化学性能和持续改进。Neurocrine 的下一代商业工艺是根据制药绿色化学原则开发的(《制药工艺研究与开发》,2006 年,10 期,315-319 页),采用了加速反应动力学、简化反应介质和消除不必要的工作程序等策略,以提高工艺效率和操作灵活性。新的绿色工艺将生产时间缩短了 43%,材料用量减少了 45%,同时将整体工艺产量提高了 5%,用水量减少了 32%,从而实现了更高的效率和可持续性。
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引用次数: 0
Going with the Flow: Implementation of a New Continuous Process for a Selective Acetal Deprotection 顺其自然:实施选择性乙缩醛脱保护的新型连续工艺
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-11 DOI: 10.1021/acs.oprd.3c00401
Adam Clarke, Heena Panchal, Jigang Yang, Yunfeng Bai, Yuedong Wu, Jinxu Sun, Zhiyuan Zhou
DB Mesylate is a common intermediate used in the production of cEt amidites, supporting part of AstraZeneca’s oligonucleotide portfolio. The current process to manufacture DB Mesylate includes eight stages with three isolated intermediates and is well understood. This paper covers the implementation of a flow process to resolve the throughput, yield, and manufacturing challenges associated with the key acetal deprotection stage.
DB Mesylate 是生产 cEt amidites 的常用中间体,为阿斯利康的寡核苷酸产品组合提供支持。目前的甲磺酸 DB 生产工艺包括八个阶段,其中有三个分离的中间体,该工艺已经非常成熟。本文介绍了如何实施流程工艺,以解决与关键乙缩醛脱保护阶段相关的产量、产率和生产难题。
{"title":"Going with the Flow: Implementation of a New Continuous Process for a Selective Acetal Deprotection","authors":"Adam Clarke, Heena Panchal, Jigang Yang, Yunfeng Bai, Yuedong Wu, Jinxu Sun, Zhiyuan Zhou","doi":"10.1021/acs.oprd.3c00401","DOIUrl":"https://doi.org/10.1021/acs.oprd.3c00401","url":null,"abstract":"DB Mesylate is a common intermediate used in the production of cEt amidites, supporting part of AstraZeneca’s oligonucleotide portfolio. The current process to manufacture DB Mesylate includes eight stages with three isolated intermediates and is well understood. This paper covers the implementation of a flow process to resolve the throughput, yield, and manufacturing challenges associated with the key acetal deprotection stage.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Application of Imine Reductase in Bioactive Chiral Amine Synthesis 亚胺还原酶在生物活性手性胺合成中的应用
IF 3.4 3区 化学 Q2 CHEMISTRY, APPLIED Pub Date : 2024-07-11 DOI: 10.1021/acs.oprd.4c00147
Zhi Wang, Guang-Sheng Gao, Ya-Dong Gao, Li-Cheng Yang
Nitrogen-containing compounds, especially those with chiral amine structures, play a pivotal role in the field of organic active pharmaceutical ingredients. Traditional racemate resolution and chemical synthesis methods for the preparation of chiral amines suffer drawbacks such as high cost and environmental pollution. Over the past decades, stereoselective synthesis of nitrogen-containing compounds by biocatalytic methods such as imine reductase (IRED)-mediated transformation has become increasingly prominent. The prominence of imine reductases lies in their capacity to catalyze the reductive amination of aldehydes or ketones with primary or secondary amines, as well as their broader substrate scope. Furthermore, imine reductases exhibit diverse catalytic cycling systems that are unaffected by adverse reaction equilibria. This article focuses on the development of drug molecules or intermediates in biocatalytic synthesis mediated by imine reductase.
含氮化合物,尤其是具有手性胺结构的含氮化合物,在有机活性药物成分领域发挥着举足轻重的作用。传统的外消旋体解析法和化学合成法制备手性胺存在成本高、环境污染等缺点。在过去几十年中,通过生物催化方法(如亚胺还原酶(IRED)介导的转化)立体选择性合成含氮化合物的研究日益突出。亚胺还原酶的显著特点在于它们能够催化醛或酮与伯胺或仲胺的还原胺化反应,而且底物范围更广。此外,亚胺还原酶表现出多样化的催化循环系统,不受不良反应平衡的影响。本文将重点介绍在亚胺还原酶介导的生物催化合成中药物分子或中间体的开发。
{"title":"Application of Imine Reductase in Bioactive Chiral Amine Synthesis","authors":"Zhi Wang, Guang-Sheng Gao, Ya-Dong Gao, Li-Cheng Yang","doi":"10.1021/acs.oprd.4c00147","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00147","url":null,"abstract":"Nitrogen-containing compounds, especially those with chiral amine structures, play a pivotal role in the field of organic active pharmaceutical ingredients. Traditional racemate resolution and chemical synthesis methods for the preparation of chiral amines suffer drawbacks such as high cost and environmental pollution. Over the past decades, stereoselective synthesis of nitrogen-containing compounds by biocatalytic methods such as imine reductase (IRED)-mediated transformation has become increasingly prominent. The prominence of imine reductases lies in their capacity to catalyze the reductive amination of aldehydes or ketones with primary or secondary amines, as well as their broader substrate scope. Furthermore, imine reductases exhibit diverse catalytic cycling systems that are unaffected by adverse reaction equilibria. This article focuses on the development of drug molecules or intermediates in biocatalytic synthesis mediated by imine reductase.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Organic Process Research & Development
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