De-epimerizing DyKAT of β-Lactones Generated by Isothiourea-Catalysed Enantioselective [2+2] Cycloaddition DOI Creative Commons

Aífe Conboy,

Alister S. Goodfellow, Kevin Kasten

et al.

Published: Jan. 29, 2024

Moderate diastereoselectivity (typically 70:30 dr) is observed in the isothiourea-catalysed [2+2]-cycloaddition of C(1)-ammonium enolates with pyrazol-4,5-diones to generate spirocyclic β lactones, but subsequent ring-opening morpholine generatesβ hydroxyamide products enhanced stereoselectivity (up >95:5 dr). Stereoconvergence diastereoisomeric β-lactones, leading a single product (>95:5 dr, >99:1 er). Mechanistic studies and DFT analysis indicate substrate controlled Dynamic Kinetic Asymmetric Transformation (DyKAT) involving epimerisation at C(3) β-lactone under reaction conditions, coupled hydrogen bond-assisted nucleophilic addition Si face stereodetermining ring-opening. The scope limitations one-pot protocol consisting enantio-determining [2+2] cycloaddition followed by diastereo-determining subsequently developed. Variation within anhydride ammonium enolate precursor, as well N(1)- C(3)- pyrazol-4,5-dione scaffold demonstrated, giving range functionalised hydroxyamides high diastereo- enantiocontrol (>20 examples, up dr er) via this DyKAT.

Language: Английский

Protein Engineering of Substrate Specificity toward Nitrilases: Strategies and Challenges DOI

Shi-Qian Bian,

Zi-Kai Wang,

Jin‐Song Gong

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Nitrilase is extensively applied across diverse sectors owing to its unique catalytic properties. Nevertheless, in industrial production, nitrilases often face issues such as low efficiency, limited substrate range, suboptimal selectivity, and side reaction products, which have garnered heightened attention. With the widespread recognition that structure of enzymes has a direct impact on their properties, an increasing number researchers are beginning optimize functional characteristics by modifying structures, order meet specific or biotechnology application needs. Particularly artificial intelligence era, innovative computer-aided design enzyme engineering offers remarkable opportunities tailor for production high-value products. In this discussion, we will briefly examine structural mechanism nitrilase. An overview protein strategies preference, regioselectivity stereoselectivity explored combined with some representative examples recently terms specificity enzyme. The future research trends field also prospected.

Language: Английский

Citations

2
Rhodium‐Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of 1,3‐Dipolar Nitrones DOI

Liren Xu,

Tilong Yang, Hao Sun

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(14)

Published: Feb. 17, 2024

Abstract Owing to their distinctive 1,3‐dipolar structure, the catalytic asymmetric hydrogenation of nitrones hydroxylamines has been a formidable and longstanding challenge, characterized by intricate enantiocontrol susceptibility N−O bond cleavage. In this study, transfer were accomplished with tethered TsDPEN‐derived cyclopentadienyl rhodium(III) catalyst (TsDPEN: p ‐toluenesulfonyl‐1,2‐diphenylethylene‐1,2‐diamine), reaction proceeds via novel 7‐membered cyclic transition state, producing chiral up 99 % yield >99 ee. The practical viability methodology was underscored gram‐scale reactions subsequent transformations. Furthermore, mechanistic investigations DFT calculations also conducted elucidate origin enantioselectivity.

Language: Английский

Citations

9
Imine Reductases and Reductive Aminases in Organic Synthesis DOI Creative Commons
Godwin A. Aleku

ACS Catalysis, Journal Year: 2024, Volume and Issue: unknown, P. 14308 - 14329

Published: Sept. 12, 2024

Language: Английский

Citations

9
Enantioselectivity Enhancement of a Geobacillus thermoleovorans CCR11 Lipase by Rational Design DOI Open Access

Aaron-Salvador Bustos-Baena,

Rodolfo Quintana‐Castro, María Guadalupe Sánchez-Otero

et al.

Catalysts, Journal Year: 2025, Volume and Issue: 15(2), P. 168 - 168

Published: Feb. 12, 2025

Lipases are enzymes that catalyze the hydrolysis of carboxylic esters at a lipid–water interface and able to reactions such as alcoholysis, esterification, transesterification, enantioselective synthesis in organic media. They important biocatalysts for biotechnological industrial applications—such food flavor industry—and production biopharmaceuticals, biofuels, biopolymers, detergents. A desirable property lipases is stereoselectivity chemicals with high optical purity. In this work, we report improvement capabilities Geobacillus thermoleovorans CCR11 lipase. By means rational design bioinformatic approaches, six amino acids catalytic cavity lipase LipTioCCR11 were substituted resulting an increase optimum temperature enzyme resistance presence solvents hydrolytic reactions, promotion recognition R isomers importance pharmaceutical industries.

Language: Английский

Citations

1
Catalytic Asymmetric Transfer Hydrogenation of Acylboronates: BMIDA as the Privileged Directing Group DOI
Xiangjian Meng,

Shouang Lan,

Ting Chen

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 20357 - 20369

Published: June 13, 2024

Developing a general, highly efficient, and enantioselective catalytic method for the synthesis of chiral alcohols is still formidable challenge. We report in this article asymmetric transfer hydrogenation (ATH) N-methyliminodiacetyl (MIDA) acylboronates as general substrate-independent entry to enantioenriched secondary alcohols. ATH acyl-MIDA-boronates with (het)aryl, alkyl, alkynyl, alkenyl, carbonyl substituents delivers variety α-boryl The latter are used range stereospecific transformations based on boron moiety, enabling carbinols two closely related α-substituents, which cannot be obtained high enantioselectivities using direct methods, such (R)-cloperastine intermediate. Computational studies illustrate that BMIDA group privileged enantioselectivity-directing Noyori–Ikariya compared conventionally aryl alkynyl groups due favorable CH–O attractive electrostatic interaction between η6-arene-CH catalyst σ-bonded oxygen atoms BMIDA. work expands domain conventional shows its huge potential addressing challenges symmetric synthesis.

Language: Английский

Citations

6
Diastereoselective Hydrogenation of Tetrasubstituted Olefins using a Heterogeneous Pt‐Ni Alloy Catalyst DOI Creative Commons

William A. Swann,

Anish Yadav,

Nicholas B. Colvin

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(19)

Published: Feb. 26, 2024

Abstract Stereoselective hydrogenation of tetrasubstituted olefins is an attractive method to access compounds with two contiguous stereocenters. However, homogeneous catalysts for enantio‐ and diastereoselective exhibit low reactivity toward due steric crowding between the ligand scaffold substrate. Monometallic heterogeneous catalysts, on other hand, provide accessible surface active sites hindered but unpredictable inconsistent stereoinduction. In this work, we develop a Pt−Ni bimetallic alloy catalyst that can diastereoselectively hydrogenate unactivated, sterically‐bulky olefins, utilizing more oxophilic Ni atoms adsorb hydroxyl directing group direct facially‐selective hydrogen addition olefin via Pt atoms. Structure‐activity studies several compositions underscore importance exposing uniform PtNi achieve high diastereoselectivity minimize side reactions. The optimized Pt−Ni/SiO 2 exhibits good functional tolerance broad scope in cyclopentene scaffold, generating cyclopentanol products three synthetic utility demonstrated four‐step synthesis (1 R ,2 S )‐(+)‐ cis ‐methyldihydrojasmonate yield enantiopurity.

Language: Английский

Citations

5
Lead-halide perovskite quantum dots embedded in mesoporous silica as heterogeneous photocatalysts combined with organocatalysts for asymmetric catalysis DOI
Hao Ren, Yiming Li, Wenjing Li

et al.

Green Chemistry, Journal Year: 2024, Volume and Issue: 26(10), P. 6068 - 6077

Published: Jan. 1, 2024

CsPbBr 3 quantum dots embedded in KIT-6 to form silica-shell-protected heterogeneous photocatalysts, which were further combined with chiral organocatalysts forming dual-catalysts explore the activity and stereoselectivity asymmetric catalysis.

Language: Английский

Citations

5
Regio- and Stereoselective Transfer Hydrogenation of Aryloxy Group-Substituted Unsymmetrical 1,2-Diketones: Synthetic Applications and Mechanistic Studies DOI
Wenjun Liu,

Caiyi Ren,

Liyuan Zhou

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 20092 - 20106

Published: July 15, 2024

Developing a general method that leads to the formation of different classes chiral bioactive compounds and their stereoisomers is an attractive but challenging research topic in organic synthesis. Furthermore, despite great value asymmetric transfer hydrogenation (ATH) both synthesis pharmaceutical industry, monohydrogenation unsymmetrical 1,2-diketones remains underdeveloped. Here, we report aryloxy group-assisted highly regio-, diastereo-, enantioselective ATH racemic 1,2-diketones. The work produces myriad enantioenriched dihydroxy ketones, further transformations furnish all eight diaryl triols, polyphenol, emblirol, glycerol-type natural products. Mechanistic studies calculations reveal two working modes group switching regioselectivity from more reactive carbonyl less one, potential on solving synthetic issues has been clearly demonstrated.

Language: Английский

Citations

5
De-epimerizing DyKAT of β-lactones generated by isothiourea-catalysed enantioselective [2 + 2] cycloaddition DOI Creative Commons

Aífe Conboy,

Alister S. Goodfellow, Kevin Kasten

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(23), P. 8896 - 8904

Published: Jan. 1, 2024

A dynamic kinetic asymmetric transformation that couples epimerisation with a hydrogen bond-assisted nucleophilic addition and stereodetermining ring-opening is investigated.

Language: Английский

Citations

4
Synthesis, Antiproliferative Activity, and ADME Profiling of Novel Racemic and Optically Pure Aryl-Substituted Purines and Purine Bioisosteres DOI Creative Commons
Martina Piškor, Astrid Milić, Sanja Koštrun

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 351 - 351

Published: Feb. 28, 2025

The aim of this study was to synthesize new racemic and optically pure aryl-substituted purine bioisosteres using ultrasound-assisted Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. Regioselective synthesis α-azido alcohols applied afford heterocycles with a 2-hydroxyeth-1-yl linker. Catalytic asymmetric halohydrin dehalogenase in the ring-opening epoxides gave enantioenriched azido alcohols, which subsequently afforded R- S-enantiomers pyrrolo[2,3-d]pyrimidines 1-hydroxyeth-2-yl newly synthesized compounds were evaluated vitro for their antiproliferative activity against four malignant tumor cell lines. influence regioisomerism stereochemistry hydroxyethyl group, as well N-heterocyclic scaffold linked aryl moiety on cytostatic evaluated. Of all tested, 40a pyrrolo[2,3-d]pyrimidine 45a derivatives p-trifluoromethyl-substituted connected 1,2,3-triazole via spacer showed promising submicromolar activity. In addition, compound exhibited selectivity towards line, index (SI) 40, moderate clearance, good membrane permeability.

Language: Английский

Citations

0