Late-Stage Halogenation of Complex Substrates with Readily Available Halogenating Reagents

Accounts of Chemical Research, Год журнала: 2024, Номер 57(21), С. 3161 - 3181

Опубликована: Сен. 20, 2024

ConspectusLate-stage halogenation, targeting specific positions in complex substrates, has gained significant attention due to its potential for diversifying and functionalizing molecules such as natural products pharmaceutical intermediates. Utilizing readily available halogenating reagents, hydrogen halides (HX), N-halosuccinimides (NXS), dichloroethane (DCE) reagents late-stage halogenation shows great promise expanding the toolbox of synthetic chemists. However, reactivity haleniums (X

Язык: Английский

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Total Enzyme Syntheses of Napyradiomycins A1 and B1

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(51), С. 17840 - 17845

Опубликована: Дек. 10, 2018

The biosynthetic route to the napyradiomycin family of bacterial meroterpenoids has been fully described 32 years following their original isolation and 11 after gene cluster discovery. antimicrobial cytotoxic natural products napyradiomycins A1 B1 are produced using three organic substrates (1,3,6,8-tetrahydroxynaphthalene, dimethylallyl pyrophosphate, geranyl pyrophosphate), catalysis via five enzymes: two aromatic prenyltransferases (NapT8 T9); vanadium dependent haloperoxidase (VHPO) homologues (NapH1, H3, H4). Building upon previous characterization NapH1, T8, we herein describe initial (NapT9, H1) final (NapH4) steps required for construction. This remarkably streamlined biosynthesis highlights utility VHPO enzymology in complex product generation, as NapH4 efficiently performs a unique chloronium-induced terpenoid cyclization establish stereocenters new carbon-carbon bond, dual-acting NapH1 catalyzes chlorination etherification reactions at distinct stages pathway. Moreover, employed recombinant enzymes chemoenzymatically synthesize milligram quantities one pot 1 day. method represents viable enantioselective approach produce halogenated metabolites, like B1, that have yet be chemically synthesized.

Язык: Английский

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Hexafluoroisopropanol‐Promoted Haloamidation and Halolactonization of Unactivated Alkenes

Angewandte Chemie International Edition, Год журнала: 2020, Номер 60(2), С. 946 - 953

Опубликована: Сен. 21, 2020

Pyrrolidine and piperidine derivatives bearing halide functional groups are prevalent building blocks in drug discovery as halides can serve an anchor for post-modifications. In principle, one of the simplest ways to build these frameworks is haloamination alkenes. While progress has been made this field, notably with development enantioselective versions, reaction still fraught limitations terms reactivity. Besides, a major question remaining understand mechanism at work. The formation haliranium intermediate typically mentioned, but limited mechanistic evidence supports it. Reported here efficient metal- oxidant-free protocol achieve haloamidation olefins, promoted by hexafluoroisopropanol, along DFT investigation mechanism. These findings should guide future more complex transformations field halofunctionalization.

Язык: Английский

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Sesquiterpene Cyclizations inside the Hexameric Resorcinarene Capsule: Total Synthesis of δ‐Selinene and Mechanistic Studies

Angewandte Chemie International Edition, Год журнала: 2019, Номер 58(36), С. 12688 - 12695

Опубликована: Июнь 27, 2019

The synthesis of terpene natural products remains a challenging task due to the enormous structural diversity in this class compounds. Synthetic catalysts are unable reproduce tail-to-head cyclization cyclase enzymes, which create from just few simple linear substrates. Recently, supramolecular structures have emerged as promising enzyme mimetics. In present study, hexameric resorcinarene capsule was utilized an artificial catalyze sesquiterpenes. With reaction key step, first total sesquiterpene product δ-selinene achieved. This represents that is based on precursor inside catalyst. To elucidate mechanism, detailed kinetic studies and isotope measurements were performed. Surprisingly, obtained data indicated rate-limiting encapsulation step operational

Язык: Английский

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Studies on the Origin of the Stabilizing Effects of Fluorinated Alcohols and Weakly Coordinated Fluorine-Containing Anions on Cationic Reaction Intermediates

The Journal of Organic Chemistry, Год журнала: 2022, Номер 87(3), С. 1814 - 1829

Опубликована: Янв. 12, 2022

Many synthetic methods that use fluorinated alcohols as solvents have been reported, and the found to be crucial success of these methods. In addition, there reports indicating adding a weakly coordinated fluorine-containing anion, such BF4-, PF6-, or SbF6-, can improve yields. The boosting effect is attributed mainly hydrogen bond activation. A few studies suggested very polar stabilize cationic reaction intermediates. However, how they do so why anions yields not studied in depth. Here, we used quaternary ammonium cations, phosphonium cation, triaryl-substituted carbocation models for short-lived intermediates possible interactions cations with SbF6-. On basis results, propose C-F dipoles E-F (where E B, P, Sb) stabilized by intermolecular charge-dipole interactions. We deduced same fashion thermodynamically

Язык: Английский

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