Synthesis of Novel Pseudo-Enantiomeric Phase-Transfer Catalysts from Cinchona Alkaloids and Application to the Hydrolytic Dynamic Kinetic Resolution of Racemic 3-Phenyl-2-oxetanone.

IF 1.5 4区 医学 Q4 CHEMISTRY, MEDICINAL Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI:10.1248/cpb.c24-00406
Midori Kawasaki, Takahiro Shirai, Kenji Yatsuzuka, Ryuichi Shirai
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Abstract

Naturally occurring Cinchona alkaloids such as quinidine (QD)/cinchonine (CN) and their diastereomers, quinine (QN)/cinchonidine (CD), have been recognized as pseudo-enantiomeric pairs. Utilizing these pseudo-enantiomeric alkaloids as chiral resources provides complementary enantioselectivity in many asymmetric reactions. During the screening of Cinchona alkaloid phase-transfer catalysts (PTCs) in the hydrolytic dynamic kinetic resolution of racemic 3-phenyl-2-oxetanone (1) to tropic acid (2), we found that the introduction of a 4-trifluoromethylphenyl group at the vinyl terminus of BnQN significantly reduced the enantioselectivity to 41% enantiomeric excess (ee). The optimized structure of tetrahedral intermediates (TI, PTC + 1 + OH-) of hydrolysis obtained by density functional theory (DFT) calculations shows that the orientation of the quinoline and benzene rings of QD class PTC are nearly parallel to each other and to construct a greatly extended π-electron cloud surface, allowing good π-π interaction with the benzene ring of 1.

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从金鸡纳生物碱中合成新型假对映异构相转移催化剂并将其应用于外消旋 3-苯基-2-氧杂环丁酮的水解动态动力学解析。
天然存在的金鸡纳生物碱(如奎尼丁(QD)/胭脂虫碱(CN)及其非对映异构体奎尼丁(QN)/胭脂虫碱(CD))已被确认为假对映异构体对。利用这些假对映生物碱作为手性资源,可以在许多不对称反应中提供互补的对映选择性。在将外消旋 3-苯基-2-氧杂环丁酮(1)水解为托品酸(2)的水解动态动力学过程中,我们筛选了金鸡纳生物碱相转移催化剂(PTC),发现在 BnQN 的乙烯基末端引入 4-三氟甲基苯基后,对映体选择性显著降低,对映体过量(ee)为 41%。密度泛函理论(DFT)计算得到的水解四面体中间体(TI、PTC + 1 + OH-)的优化结构显示,QD 类 PTC 的喹啉环和苯环的取向几乎相互平行,并构建了一个极大扩展的 π 电子云表面,从而与 1 的苯环产生良好的 π-π 相互作用。
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来源期刊
CiteScore
3.20
自引率
5.90%
发文量
132
审稿时长
1.7 months
期刊介绍: The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below. Topics: Organic chemistry In silico science Inorganic chemistry Pharmacognosy Health statistics Forensic science Biochemistry Pharmacology Pharmaceutical care and science Medicinal chemistry Analytical chemistry Physical pharmacy Natural product chemistry Toxicology Environmental science Molecular and cellular biology Biopharmacy and pharmacokinetics Pharmaceutical education Chemical biology Physical chemistry Pharmaceutical engineering Epidemiology Hygiene Regulatory science Immunology and microbiology Clinical pharmacy Miscellaneous.
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