Accelerating Drug Discovery: Synthesis of Complex Chemotypes via Multicomponent Reactions

ACS Medicinal Chemistry Letters, Год журнала: 2023, Номер 14(4), С. 376 - 385

Опубликована: Март 8, 2023

The generation of multiple bonds in one reaction step has attracted massive interest drug discovery and development. Multicomponent reactions (MCRs) offer the advantage combining three or more reagents a one-pot fashion to effectively yield synthetic product. This approach significantly accelerates synthesis relevant compounds for biological testing. However, there is perception that this methodology will only produce simple chemical scaffolds with limited use medicinal chemistry. In Microperspective, we want highlight value MCRs toward complex molecules characterized by presence quaternary chiral centers. paper cover specific examples showing impact technology clinical recent breakthroughs expand scope topologically rich molecular chemotypes.

Язык: Английский

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Accessing unnatural α-amino acids with tetrasubstituted stereogenic centersviacatalytic enantioselective reactions of ketimine-type α-iminoesters/α-iminoamides

Chemical Communications, Год журнала: 2023, Номер 59(54), С. 8343 - 8374

Опубликована: Янв. 1, 2023

Catalytic enantioselective synthesis methodologies have been actively explored and developed owing to the significance of chiral molecules their utilities. In particular, unnatural α-amino acids with tetrasubstituted stereogenic carbon centers (α-tertiary amino acids; ATAAs) are undoubtedly among most valuable compounds. Asymmetric addition an α-iminoester or α-iminoamide is widely recognized as a straightforward, powerful, atom-economical strategy for accessing optically active derivatives. However, this type chemistry, which relies on ketimine-type electrophiles, was quite limited only few decades ago low reactivities difficulties associated enantiofacial control. This feature article comprehensively overviews research field highlights significant progress that has made. it focuses catalyst system transition state key parameters such reactions.

Язык: Английский

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Organocatalytic Synthesis of α-Aminonitriles: A Review

Catalysts, Год журнала: 2022, Номер 12(10), С. 1149 - 1149

Опубликована: Окт. 1, 2022

α-Aminonitriles, which have anticancer, antibacterial, antiviral, and antifungal properties, played an important role in pharmacology. Furthermore, they can also be used to synthesize natural unnatural amino acids. The main bottleneck the commercialization of these products is their large-scale production with controlled chirality. A variety methods been α-aminonitriles. Among other reported for preparing α-aminonitriles, Strecker reaction considered appropriate. Recent developments, however, enabled α-cyanation tertiary secondary amines by functionalizing carbon–hydrogen (C–H) bond as attractive alternative procedure preparation α-aminonitriles presence oxidant a cyanide source. In most cases, reactions are catalyzed transition metal catalysts, such Fe, Cu, Rh, V, Au, Ru, Mo, Pt, Re, Co, or photocatalysts. As alternative, organocatalysts produce aminonitriles. Although there numerous reviews on no published specifically organocatalyzed synthesis Organocatalysis plays significant synthesizing via Strecker-type cross dehydrogenative coupling (CDC). this mini review, we discuss molecules. review new aminonitriles expected provide insight into development industrial catalysts.

Язык: Английский

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Asymmetric Cyanation of α-Ketimino Ester Derivatives with Chiral Ru–Li Combined Catalysts

Organic Letters, Год журнала: 2024, Номер 26(4), С. 900 - 905

Опубликована: Янв. 22, 2024

Asymmetric cyanation of α-ketimino esters catalyzed by combined systems amino acid/BINAP derivative/Ru(II) complexes and lithium compounds was examined. The use an appropriate combination acid BINAP ligands achieved high enantioselectivity for a variety α-alkynyl (Val/XylBINAP/Ru), α-alkenyl (Val/TolBINAP/Ru), α-aryl imino (Val/XylBINAP/Ru) as well isatin-derived cyclic amide (t-Leu/BINAP/Ru) to afford the α-cyano-α-amino with α-nitrogen-substituted quaternary chiral center up 98% ee.

Язык: Английский

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Enantioselective Reaction of N-Unprotected Activated Ketimines with Phosphine Oxides Catalyzed by Chiral Imidazoline-Phosphoric Acids

Organic Letters, Год журнала: 2022, Номер 24(43), С. 8088 - 8092

Опубликована: Окт. 24, 2022

The first enantioselective hydrophosphonylation of ketimines with phosphine oxides was developed. reaction unprotected using a bis(imidazoline)-phosphoric acid catalyst gave chiral α-quaternary aminophosphorous compounds having primary amino group in excellent yields and enantioselectivities. Based on experimental results DFT calculation, transition states were proposed to explain the stereoselectivity reaction.

Язык: Английский

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Photocatalytic Strecker-Type Reaction for the Synthesis of Primary α-Aminonitriles

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

A practical photoinduced direct N–O cleavage of oxime ethers via a single electron transfer (SET) process was developed, enabling controlled generation N–H imines iminyl radical intermediates. By employing this strategy, an efficient Strecker-type reaction established to construct variety primary α-aminonitriles using TMSCN as cyanide source. This protocol showed exceptional tolerance various functional groups, delivering the corresponding products in good yields. Mechanistic investigations indicate involvement radicals and radical/polar crossover sequence.

Язык: Английский

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Catalytic Asymmetric Synthesis of C-Chiral Phosphonates

Symmetry, Год журнала: 2022, Номер 14(9), С. 1758 - 1758

Опубликована: Авг. 23, 2022

The current review is devoted to the achievements in development of methods for catalytic asymmetric synthesis phosphonates containing a chiral center side chain. C-chiral are widely represented among natural compounds with various biological activities as insecticides, herbicides, antibiotics, and bioregulators. Synthetic representatives this class have found practical application biologically active compounds. summarizes metal complex catalysis organocatalysis applied such reactions phospha-aldol reaction, two-component three-component phospha-Mannich phospha-Michael well hydrogenation unsaturated phosphine oxides, ketophosphonates, iminophosphonates. Methods hydride reduction C=X (X=O, S, NR) also discussed detail. presents updated literature reports, original research by author.

Язык: Английский

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Multicomponent Synthesis of 5‐Cyano‐pyrazolo[1,5‐a]pyrimidines Enabled by Aerobic Manganese Catalysis

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(6), С. 871 - 876

Опубликована: Фев. 28, 2023

An aerobic Mn(III)-catalyzed one-pot three-component synthesis of 5-cyano-pyrazolo[1,5-a]pyrimidines has been described. The synergistic combination Strecker reaction and oxidatively-induced 6π-azacyclization is the key to success this multicomponent synthesis. Differing from previous reports relied on toxic cyanating agents or multistep synthesis, mechanistically distinct protocol serves as a step-economic, regioselective functionally tolerant strategy obtain 5-cyano-pyrazolo[1,5-a]pyrimidines. As service our authors readers, journal provides supporting information supplied by authors. Such materials are peer reviewed may be re-organized for online delivery, but not copy-edited typeset. Technical support issues arising (other than missing files) should addressed Please note: publisher responsible content functionality any Any queries content) directed corresponding author article.

Язык: Английский

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Organocatalytic Direct Enantioselective Hydrophosphonylation of N-Unsubstituted Ketimines for the Synthesis of α-Aminophosphonates

ACS Catalysis, Год журнала: 2023, Номер 13(5), С. 3158 - 3163

Опубликована: Фев. 17, 2023

We report an organocatalyzed direct enantioselective hydrophosphonylation of N-unsubstituted ketimines that affords N-unprotected α-tetrasubstituted α-aminophosphonates without protection/deprotection steps. The reaction is suitable for isatin-derived and trifluoromethyl ketimines, affording products in high yields with excellent enantioselectivity. Applications the a proposed transition state model are also described.

Язык: Английский

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Tandem Strecker/C(sp³)–H amination reactions for the construction of cyanide-functionalized imidazo[1,5-a]pyridines with NH₄SCN as a cyanating agent

Organic Chemistry Frontiers, Год журнала: 2021, Номер 8(22), С. 6384 - 6389

Опубликована: Янв. 1, 2021

An I 2 O 5 -mediated multicomponent reaction that allows the single-step construction of cyano-functionalized imidazo[1,5- a ]pyridines with molecular diversity was realized for first time.

Язык: Английский

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