Total Synthesis of Gukulenin B via Sequential Tropolone Functionalizations

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(11), С. 5190 - 5196

Опубликована: Март 11, 2022

The synthesis of functionalized aromatic compounds is a central theme research for modern organic chemistry. Despite the increasing finesse in functionalization five- and six-membered rings, their seven-membered-ring sibling, tropolone (2-hydroxy-2,4,6-cycloheptatrien-1-one), remains challenging target synthetic derivatization. This challenge primarily emanates from unique structural chemical properties tropolonoid compounds, which often lead to unexpected undesired reaction outcomes under conditions developed functionalizations other moieties. Herein, we describe total one most complex natural tropolonoids, gukulenin B. Our route features series site-selective C–H bond C–C formations, whose are judiciously tuned allow uncompromised performance on nucleus. flexibility modularity our expected facilitate further biological studies family cytotoxins. In addition, methods tactics herein moiety could inspire enable chemists multiple disciplines take advantage this privileged yet underexplored motif.

Язык: Английский

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Computational methods and points for attention in absolute configuration determination

Frontiers in Natural Products, Год журнала: 2023, Номер 1

Опубликована: Янв. 12, 2023

With the rapid development of high performance computers and computational methods, including software, an increasing number experimental chemists have tried to use methods such as optical rotation (OR, matrix model), rotatory dispersion (ORD), electronic circular dichroism (ECD or CD), vibrational (VCD), magnetic shielding constants—nuclear resonance (NMR)—to explain and/or assign absolute configuration (AC) for various compounds. Such reports in field natural products increased dramatically. However, every method has its range application. This leads, some cases, incorrect conclusions by researchers who are not familiar with these methods. In this review, we provide more details suitable suggestions, especially hope that experience may help readers avoid pitfalls. Finally, discuss simplified models replace original complex structures a long side chain. The fundamental basis using represent chiral compounds, OR calculations, is existence conformation pairs near canceling conformer contributions justify rather than Using examples, here introduce transition state (TS) calculation, which benefit area mastery their AC study. review will summarize general concepts involved study determinations.

Язык: Английский

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Phosphine-catalyzed formal Buchner [6+1] annulation: de novo construction of cycloheptatrienes

Chemical Communications, Год журнала: 2023, Номер 59(88), С. 13215 - 13218

Опубликована: Янв. 1, 2023

A new method is developed to construct cycloheptatriene derivatives efficiently by phosphine-catalyzed formal Buchner [6+1] annulation of a newly designed allenoate and 4-oxo-4 H -chromene-3-carbaldehydes.

Язык: Английский

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Electrochemical Site‐Selective Alkylation of Tropones via Formal C(sp³)−C(sp²) Coupling Reaction

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(9), С. 1965 - 1971

Опубликована: Март 5, 2024

Abstract The first site‐selective electrochemical alkylation of tropones is realized by reacting 2‐acetoxytropones and redox‐active‐esters (RAEs). electroreductive protocol enables the preparation mono‐ disubstituted in high yields (up to 71%) under very mild conditions. Dedicated voltammetric measurements served for identification as a class valuable trapping agents nucleophilic radical species shed light on whole mechanistic profile. Wide tolerance towards functional groups (27 examples) application late‐stage functionalization bioactive compound ( i. e . Colchicine analogue), emphasize synthetic impact present methodology.

Язык: Английский

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A Benchmark Study of Quantum Mechanics and Quantum Mechanics-Molecular Mechanics Methods for Carbocation Chemistry

Journal of Chemical Theory and Computation, Год журнала: 2021, Номер 18(1), С. 167 - 178

Опубликована: Дек. 14, 2021

Carbocations play key roles in classical organic reactions and have also been implicated several enzyme families. A hallmark of carbocation chemistry is multitudes competing reaction pathways, to be able distinguish between pathways with quantum chemical calculations, it necessary approach accuracy for relative energies carbocations. Here, we present an extensive study the performance selected density functional theory (DFT) methods describing thermochemistry kinetics carbocations their corresponding neutral alkenes both gas-phase within a hybrid mechanics-molecular mechanics (QM/MM) framework. The functionals are benchmarked against accurate ab initio such as CBS-QB3 DLPNO-CCSD(T). Based on findings calculations alkenes, best chosen tested further non-covalent interactions model systems using QM QM/MM methods. We compute interaction carbocation/alkane π, dipole, hydrophobic DFT QM(DFT)/MM compare These latter representative side chains amino acids phenylalanine/tyrosine, tryptophan, asparagine/glutamine, serine/threonine, methionine, other groups. Lennard-Jones parameters atoms modified obtain optimal fit energies. Finally, studied gas phase implicit chloroform solvent explicit umbrella sampling simulations. This highlights highest possible but some limitations systems.

Язык: Английский

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Understanding and Engineering the Stereoselectivity of Humulene Synthase

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(37), С. 20308 - 20312

Опубликована: Июнь 28, 2021

The non-canonical terpene cyclase AsR6 is responsible for the formation of 2E,6E,9E-humulene during biosynthesis tropolone sesquiterpenoid (TS) xenovulene A. structures unliganded and in complex with an crystallo cyclized reaction product thiolodiphosphate reveal a new farnesyl diphosphate binding motif that comprises unique binuclear Mg2+ -cluster essential K289 residue conserved all humulene synthases involved TS formation. Structure-based site-directed mutagenesis its homologue EupR3 identify single residue, L285/M261, controls production either 2E,6E,9E- or 2Z,6E,9E-humulene. A possible mechanism observed stereoselectivity was investigated using different isoprenoid precursors results demonstrate M261 has gatekeeping control over

Язык: Английский

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Enzymatic intermolecular Diels-Alder reactions in synthesis: From nature to design

Tetrahedron Chem, Год журнала: 2022, Номер 2, С. 100013 - 100013

Опубликована: Апрель 26, 2022

The Diels-Alder (D-A) reaction is one of the most critical chemical transformations to construct C–C bonds with predictable regio- and stereo-selectivities. It has been widely used as a retrosynthetic disconnection in synthetic chemistry. Although significant advances have made, challenges remain how precisely control stereochemistry intermolecular reaction. Enzymes are well known for their remarkable catalytic efficiency selectivity compared chemo-catalysts. Therefore, identifying designing Diels-Alderases that can be organic synthesis received considerable attention from community. In this review, we review all enzymes capable catalyzing formal reactions natural product biosynthetic pathways, discuss mechanisms detail, highlight potential precise efficient enantiopure D-A products. We also different strategies create new artificial Diels-Alderases, especially RNA-based Diels-Alderases.

Язык: Английский

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Exploring the Chemical Space Accessed by Chiral Pool Terpenes. The (−)-Caryophyllene Oxide Paradigm

Organic Letters, Год журнала: 2024, Номер 26(15), С. 2897 - 2901

Опубликована: Март 29, 2024

Terpenes represent a flourishing source of structural motifs that can be converted into several more complex architectures. Realization such transformations in concise and efficient manner adds great value to the starting material. Herein, we study case (−)-caryophyllene oxide convert it natural sesquiterpenoids (rumphellolide K, rumphellaone A, antipacid A), thus expanding chemical space accessed by its privilege structure. Our semisyntheses are short rely on reagent-dictated stereo- chemoselectivity.

Язык: Английский

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Structural Revisions of Macrocyclic Ellagitannin Dimers Bridged by Two Hexahydroxydiphenoyl Groups

Tetrahedron, Год журнала: 2025, Номер unknown, С. 134751 - 134751

Опубликована: Май 1, 2025

Язык: Английский

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Troponoid Compounds as Therapeutic Agents and as Targets and Templates for Chemical Synthesis

Synlett, Год журнала: 2022, Номер 33(20), С. 1968 - 1990

Опубликована: Авг. 16, 2022

Abstract The renewed interest in troponoid compounds as potential therapeutic agents and the ongoing discovery of new, naturally occurring biologically active members class has resulted an attendant focus on developing deploying methods for their synthesis. This account highlights some significant recent developments area chemistry that serve to contextualize our group’s longstanding synthesis such through cyclopropane-mediated ring-expansion cyclohexanoid benzenoid compounds. various means by which conversions can be accomplished application both natural non-natural troponoids are detailed. 1 Introduction 2 Naturally Occurring Troponoid Compounds Their Biogenesis 3 Medicinal Chemistry Aspects 4 Troponoids Materials Science 5 Scaffolds Chemical Synthesis 6 An Overview Methods Available Preparing 7 Cyclopropane-Mediated Ring-Expansion Reactions Leading 8 Conclusions

Язык: Английский

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