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Cycloadditions of nitrones with alkynes usually occur best under heat activation. Due to the instability of the formed isoxazolines, alternative activation methods must be found. Here, hyperbaric conditions are used to transform nitrones generated from unprotected carbohydrates into the corresponding polyhydroxy-isoxazolines at room temperature. The reaction proved completely regioselective in favor of the 5-substituted 4-isoxazolines, and the products are obtained in good yields as mixtures of the two possible diastereoisomers. Further transformations into biologically valuable targets are described. The whole synthesis constitutes a very straightforward procedure for the transformation of aldoses, and is highly compatible with the principles of green chemistry. [ABSTRACT FROM AUTHOR]

The diastereoselective access to cyclopentanols and N,O‐dimethylcyclopentylhydroxylamines from 4‐pentenoic acid‐derived Weinreb amides is described. Based on the concomitant generation of both the nucleophilic and the electrophilic poles by hydrozirconation of the amide and the C=C double bond, the cyclisation may be tuned towards cyclopentanols or N,O‐dimethylcyclopentylhydroxylamines depending on the ring‐closure promotor. An extension to cis 3‐substituted N,O‐dimethylcyclohexylhydroxylamines is also presented. [ABSTRACT FROM AUTHOR]

IspG (also called GcpE) is an oxygen-sensitive [4Fe-4S] enzyme catalyzing the penultimate step of the methylerythritol phosphate (MEP) pathway, a validated target for drug development. It converts 2-C-methyl-d-erythritol-2,4-cyclo-diphosphate (MEcPP) into (E)-4-hydroxy-3-methyl-but-2-enyl-1-diphosphate (HMBPP). The reaction, assimilated to a reductive dehydration, involves redox partners responsible for the formal transfer of two electrons to substrate MEcPP. The 2-vinyl analogue of MEcPP was designed to generate conjugated species during enzyme catalysis, with the aim of providing new reactive centers to be covalently trapped by neighboring amino acid residues. The synthesized substrate analogue displayed irreversible inhibition towards IspG. Furthermore, we have shown that electron transfer occurs prior to inhibition; this might designate conjugated intermediates as probable affinity tags through covalent interaction at the catalytic site. This is the first report of an irreversible inhibitor of the IspG metalloenzyme., (© 2022 Wiley-VCH GmbH.)

The diastereoselective access to cyclopentanols and N,O-dimethylcyclopentylhydroxylamines from 4-pentenoic acid-derived Weinreb amides is described. Based on the concomitant generation of both the nucleophilic and the electrophilic poles by hydrozirconation of the amide and the C=C double bond, the cyclisation may be tuned towards cyclopentanols or N,O-dimethylcyclopentylhydroxylamines depending on the ring-closure promotor. An extension to cis 3-substituted N,O-dimethylcyclohexylhydroxylamines is also presented., (© 2021 Wiley-VCH GmbH.)