Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

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Toward the Generation of 2-Amino-3-Formyl Difunctionalized Chromones via Pd-Enabled Rearrangement Strategy

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(19), P. 12692 - 12699

Published: Sept. 14, 2023

Accomplished herein is a rearrangement strategy for the highly efficient assembly of synthetically cumbersome while medicinally significant 2-amino-3-formyl chromones via palladium-catalyzed ring-opening, rearrangement, and cyclization process. Such sequence enables formation one C(sp2)–O bond C(sp2)–C(sp2) bond, reconstruction benzo-γ-pyrone moiety in single operation, thus producing difunctionalized chromone-incorporated derivatives. The reaction proceeds shorter time (30 min 3-iodochromones most cases) atom- step-economical manner. synthetic application current protocol further demonstrated by late-stage modification pharmaceuticals their intermediates, gram-scale reactions, transformations functional groups, as well synthesis bioactive molecules drugs. Mechanistic studies indicate that nucleophilic ring-opening process moiety, phenoxy anion intermediate, an intramolecular might be involved present system.

Language: Английский

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Selective P450_BM3 Hydroxylation of Cyclobutylamine and Bicyclo[1.1.1]pentylamine Derivatives: Underpinning Synthetic Chemistry for Drug Discovery

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(50), P. 27767 - 27773

Published: Dec. 5, 2023

Achieving single-step syntheses of a set related compounds divergently and selectively from common starting material affords substantial efficiency gains when compared with preparing those same by multiple individual syntheses. In order for this approach to be realized, complementary reagent systems must available; here, panel engineered P450BM3 enzymes is shown fulfill remit in the selective C–H hydroxylation cyclobutylamine derivatives at chemically unactivated sites. The oxidations can proceed high regioselectivity stereoselectivity, producing valuable bifunctional intermediates synthesis applications fragment-based drug discovery. process also applies bicyclo[1.1.1]pentyl (BCP) amine achieve first direct enantioselective functionalization bridging methylenes open short efficient route chiral BCP bioisosteres medicinal chemistry. combination substrate, enzyme, reaction engineering provides powerful general platform small-molecule elaboration diversification.

Language: Английский

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Carbon–nitrogen transmutation in polycyclic arenol skeletons to access N-heteroarenes

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 4, 2024

Abstract Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in ring system without altering size even more challenging. Here, we introduce strategy that enables polycyclic arenols, highly prevalent motif bioactive molecules, to be readily converted into N -heteroarenes through carbon–nitrogen transmutation. The reaction features selective nitrogen insertion C–C bond of arenol frameworks by azidative dearomatization aryl migration, followed ring-opening, ring-closing (ANRORC) achieve carbon-to-nitrogen aromatic framework arenol. Using widely available arenols as -heteroarene precursors, this alternative approach allows streamlined assembly complex heteroaromatics with broad functional group tolerance. Finally, pertinent transformations products, including synthesis biheteroarene skeletons, were conducted exhibited significant potential materials chemistry.

Language: Английский

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Recent Progress in Accessing Multi-functionalized Caged Hydrocarbons: En Route to Highly Functionalized Saturated (Bio)isosteres of Benzene Rings

Synthesis, Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Abstract Recently, many saturated bioisosteres of the benzene ring have been developed, and their applications in drug development evaluated. Most these are caged hydrocarbons, which rigid skeletons three-dimensional spaces. Recent efforts to synthesize hydrocarbons enabled access multi-functionalized congeners that expected be (bio)isosteres benzenes. This short review summarizes recently reported methods for obtaining (typically more than disubstituted) hydrocarbons. 1 Introduction 2 Proposed Structures Caged Hydrocarbons as Saturated (Bio)isosteres Benzene Ring: A Brief Summary 3 Access Multi-functionalized Hydrocarbons: De Novo Synthetic Approaches 3.1 Bicyclo[1.1.1]pentanes (BCPs) 3.2 Bicyclo[2.1.1]hexanes (BCHs) 3.3 Bicyclo[3.1.1]heptanes (BCHeps) 3.4 Others 4 C–H Functionalization 5 Conclusion

Language: Английский

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