Photochemical Synthesis of Nucleoside Analogues from Cyclobutanones: Bicyclic and Isonucleosides

Jaffer, Mileina; Ebead, Abdelaziz; Lee‐Ruff, Edward

doi:10.3390/molecules15063816

Cited by 13 publications

(6 citation statements)

References 25 publications

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“…While ring-opening reactions of cyclobutanones are well known, 40 the only example of an α-heteroatom-substituted cyclobutanone ring opening to a butyric acid derivative that we are aware of is of 2,2-dibromocyclobutanone opening to give 4,4-dibromobutyric acid when treated with strongly nucleophilic alkanoates including methoxide, 41 whereas the only similar fragmentation of an α-aminocyclobutanone derivative was observed photochemically. 42 We sought to explore conditions that might promote the opening of cyclobutanone (±)-5 to give 6 including Fenton's reagent 43 that initiates the production of hydroxyl radicals in situ, but the treatment of cyclobutanone (±)-5 under these conditions gave no detectable trace of 6 by HPLC, which is perhaps not surprising given the highly reactive properties of Fenton's reagent, which could further degrade the compound. Forced degradation of cyclobutanone (±)-5 with either pyridine N-oxide or with the free-radical TEMPO also did not yield 6 (MH + = 258) by HPLC/MS but rather afforded a product of a probable Baeyer−Villiger oxidation and hydrolytic ring opening.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Cyclobutanone Inhibitor of Cobalt-Functionalized Metallo-γ-Lactonase AiiA with Cyclobutanone Ring Opening in the Active Site

et al. 2021

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An α-amido cyclobutanone possessing a C10 hydrocarbon tail was designed as a potential transition-state mimetic for the quorum-quenching metallo-γ-lactonase autoinducer inactivator A (AiiA) with the support of in-house modeling techniques and found to be a competitive inhibitor of dicobalt(II) AiiA with an inhibition constant of K i = 0.007 ± 0.002 mM. The catalytic mechanism of AiiA was further explored using our product-based transition-state modeling (PBTSM) computational approach, providing substrate-intermediate models arising during enzyme turnover and further insight into substrate–enzyme interactions governing native substrate catalysis. These interactions were targeted in the docking of cyclobutanone hydrates into the active site of AiiA. The X-ray crystal structure of dicobalt(II) AiiA cocrystallized with this cyclobutanone inhibitor unexpectedly revealed an N-(2-oxocyclobutyl)decanamide ring-opened acyclic product bound to the enzyme active site (PDB 7L5F). The C10 alkyl chain and its interaction with the hydrophobic phenylalanine clamp region of AiiA adjacent to the active site enabled atomic placement of the ligand atoms, including the C10 alkyl chain. A mechanistic hypothesis for the ring opening is proposed involving a radical-mediated process.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Cyclobutanone Inhibitor of Cobalt-Functionalized Metallo-γ-Lactonase AiiA with Cyclobutanone Ring Opening in the Active Site

et al. 2021

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“…[47] In 2010, the same group reported N-glycosylation by the photochemical ring-expansion of cyclobutanones during the synthesis of bicyclic nucleoside analogues (Scheme 11C). [48] These transforma- tions are amazing, but the need to use UV light has limited their applications.…”

Section: Reactions With Oxycarbenes Derived From Cyclic Ketonesmentioning

confidence: 99%

Electron‐Rich Oxycarbenes: New Synthetic and Catalytic Applications beyond Group 6 Fischer Carbene Complexes

2023

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Oxycarbenes have emerged as useful intermediates in synthetic chemistry. Compared to the widely studied oxycarbene metal complexes bearing Group 6 metals, the synthetic and catalytic applications of oxycarbenes beyond Group 6 Fischer carbene complexes are less explored because of the difficulty in controlling their reactivity and the need to use a stoichiometric amount of a presynthesized Group 6 metal carbene complex as the starting material. This Minireview summarizes early synthetic and catalytic applications of late-transition-metal oxycarbene complexes and highlights recent advances in free oxycarbene reactions and transition-metal-catalyzed reactions involving oxycarbenes. We hope this Minireview will inspire further developments in this emerging area.

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“…The literature of the new kinds of nucleosides is increasing and a lot of variations and kinds of nucleosides with dinuclear nucleosides [12,13] and others were also reported. [14,15] The wide occurrences of heterocyclic compounds in bioactive natural products and pharmaceuticals have made them as important synthetic targets. The 1,2,4-triazoles and 1,3,4oxadiazoles represent classes of heterocyclic compounds of great importance in biological chemistry.…”

Section: Introductionmentioning

confidence: 99%

Computational Study of some Double Headed Acyclo-C-Nucleosides

Amara

Tchouar

Belaidi

2015

ILCPA

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In the present paper we have a focus in a study of theoretical characterization of three double headed acyclo-C-nucleosides, which are a recent target of experimental studies. The structural and electronic properties of double headed acyclo-C-nucleosides, 1,4-bis (3-mercapto-1H-1,2,4-triazol-5-yl) butane-1,2,3,4-tetrol, 1,4-bis (4-amino-5-mercapto-4H-1,2,4-triazol-3-yl) butane-1,2,3,4-tetrol and 5,5'-(1,2,3,4-tetrahydroxybutane-1,4-diyl) bis (1,3,4-oxadiazole-2(3H)-thione), have been investigated theoretically by performing semi-empirical molecular orbital, ab initio Hartree-Fock (HF) and Density Functional Theory (DFT) calculations. Geometries of the three molecules are optimized at the level of Austin Model 1 (AM1). The electronic properties and relative energies of the molecules have been calculated by HF and DFT in the ground state.

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Photochemical Synthesis of Nucleoside Analogues from Cyclobutanones: Bicyclic and Isonucleosides

Cited by 13 publications

References 25 publications

Cyclobutanone Inhibitor of Cobalt-Functionalized Metallo-γ-Lactonase AiiA with Cyclobutanone Ring Opening in the Active Site

Cyclobutanone Inhibitor of Cobalt-Functionalized Metallo-γ-Lactonase AiiA with Cyclobutanone Ring Opening in the Active Site

Electron‐Rich Oxycarbenes: New Synthetic and Catalytic Applications beyond Group 6 Fischer Carbene Complexes

Computational Study of some Double Headed Acyclo-C-Nucleosides

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