- Deeper insight into protease-sensitive "covalent-assembly" fluorescent probes for practical biosensing applications
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We report a rational and systematic study devoted to the structural optimisation of a novel class of protease-sensitive fluorescent probes that we recently reported (S. Debieu and A. Romieu, Org. Biomol. Chem., 2017, 15, 2575-2584), based on the "covalent-assembly" strategy and using the targeted enzyme penicillin G acylase as a model protease to build a fluorescent pyronin dye by triggering a biocompatible domino cyclisation-aromatisation reaction. The aim is to identify ad hoc probe candidate(s) that might combine fast/reliable fluorogenic "turn-on" response, full stability in complex biological media and ability to release a second molecule of interest (drug or second fluorescent reporter), for applications in disease diagnosis and therapy. We base our strategy on screening a set of active methylene compounds (C-nucleophiles) to convert the parent probe to various pyronin caged precursors bearing Michael acceptor moieties of differing reactivities. In vitro stability and fluorescent enzymatic assays combined with HPLC-fluorescence analyses provide data useful for defining the most appropriate structural features for these fluorogenic scaffolds depending on the specifications inherent to biological application (from biosensing to theranostics) for which they will be used.
- Renault, Kévin,Debieu, Sylvain,Richard, Jean-Alexandre,Romieu, Anthony
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- Regioselectivity Influences in Platinum-Catalyzed Intramolecular Alkyne O-H and N-H Additions
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The steric and electronic drivers of regioselectivity in platinum-catalyzed intramolecular hydroalkoxylation are elucidated. A branch point is found that divides the process between 5-exo and 6-endo selective processes, and enol ethers can be accessed in good yields for both oxygen heterocycles. The main influence arises from an electronic effect, where the alkyne substituent induces a polarization of the alkyne that leads to preferential heteroatom attack at the more electron-deficient carbon. The electronic effects are studied in other contexts, including hydroacyloxylation and hydroamination, and similar trends in directionality are predominant although not uniformly observed.
- Costello, Jeff P.,Ferreira, Eric M.
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supporting information
p. 9934 - 9939
(2019/12/24)
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- Efficient and expeditious chemoselective BOC protection of amines in catalyst and solvent-free media
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A green and eco-friendly route for the almost quantitative BOC protection of a large variety of aliphatic and aromatic amines, amino acids, and amino alcohols is reported in catalyst and solvent-free media under mild reaction conditions. The products were confirmed by 1H, 13C NMR, IR spectroscopy, and in some cases, elemental analysis. This protocol does not require any water quenches, solvent separations, and purification steps, such as recrystallization and column chromatography.
- Viswanadham, Balaga,Mahomed, Abdul S.,Friedrich, Holger B.,Singh, Sooboo
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p. 1355 - 1363
(2017/02/15)
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- Unsaturated amides derived from 2-amino-3-hydroxycyclopentenone: A Stille approach to the synthesis of asuka-mABA, 2880-II, and limocrocin
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A Stille palladium catalysed vinyl halide-vinyl stannane or aryl stannane coupling approach to the title compounds is described. The 2- aminocyclopentanedione-derived vinyl bromides (12, n = 1, 2, 3) were prepared and coupled to synthesise 2880-II (4), a Streptomyces metabolite, asuka-mABA (6), obtained during investigations to elucidate the biogenesis of the antibiotic asukamycin, and limocrocin (10), a naturally occurring antibiotic and antiviral agent.
- Macdonald, Gregor,Alcaraz, Lilian,Wei, Xudong,Lewis, Norman J.,Taylor, Richard J. K.
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p. 9823 - 9836
(2007/10/03)
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- A Stille approach to unsaturated amides derived from 2-amino-3-hydroxycyclopentenone: The synthesis of asuka-mABA and limocrocin
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A Stille palladium-catalysed vinyl halide-vinyl stannane coupling approach to the title compounds is described.
- Macdonald, Gregor,Lewis, Norman J.,Taylor, Richard J. K.
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p. 2647 - 2648
(2007/10/03)
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