Chirality: a key parameter in chemical probes

McGown, Andrew; Nafie, Jordan; Otayfah, Mohammed; Hassell-Hart, Storm; Tizzard, Graham J.; Coles, Simon J.; Banks, Rebecca; Marsh, Graham P.; Maple, Hannah J.; Kostakis, George E.; Proietti Silvestri, Ilaria; Colbon, Paul; Spencer, John

doi:10.1039/d3cb00082f

Cited by 4 publications

(1 citation statement)

References 24 publications

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“…Knowing the exact spatial arrangement of compounds, either newly synthetized or isolated from natural sources, is fundamental knowledge for the study of their properties not only in the pharmaceutical industry and medicine but also in organic chemistry, biochemistry, and materials science [1][2][3][4][5][6][7][8]. Furthermore, for chiral compounds, the absolute configuration must be known.…”

Section: Introductionmentioning

confidence: 99%

Conformational and Chiroptical Properties of Salicylamide-Based Peptidomimetics

Raich,

Pauk,

Imramovsky

et al. 2024

Symmetry

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Optical rotation (OR), the most frequently used chiroptical method, is used for the characterization of newly synthesized or isolated compounds. Computational predictions of OR are, however, mainly used for the determination of the absolute configurations of chiral compounds, but they may also be used for the verification of conformational analysis results if the experimental values are known. Our computational study deals with the conformational analysis of flexible salicylamide-based peptidomimetics, starting with a conformation search, then a low-level ab initio preoptimization of the hundreds of conformations found, and, finally, a higher-level DFT optimization. For the resulting minima structures, Boltzmann populations were calculated, followed by OR calculations for all the populated conformers using the DFT method with various basis sets with diffuse functions. Weighted averages of the ORs were compared with experimental values, and the agreement, which ranged from excellent to moderate for various compounds, served as a verification of the conformational analysis results.

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Section: Introductionmentioning

confidence: 99%

Conformational and Chiroptical Properties of Salicylamide-Based Peptidomimetics

Raich,

Pauk,

Imramovsky

et al. 2024

Symmetry

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Facile Synthesis of a Lipid-compatible, Dual-functionalised, and Enantiospecific Photoactivatable Linker

Marinucci,

Liu

2024

Tetrahedron Letters

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Stereo-Differentiating Asymmetric Rh(I)-Catalyzed Pauson–Khand Reaction: A DFT-Informed Approach to Thapsigargin Stereoisomers

Haghighi,

Jesikiewicz,

Stahl

et al. 2024

J. Am. Chem. Soc.

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We report a stereo-differentiating dynamic kinetic asymmetric Rh(I)-catalyzed Pauson−Khand reaction, which provides access to an array of thapsigargin stereoisomers. Using catalyst-control, a consistent stereochemical outcome is achieved at C2�for both matched and mismatched cases�regardless of the allene-yne C8 stereochemistry. The stereochemical configuration for all stereoisomers was assigned by comparing experimental vibrational circular dichroism (VCD) and 13 C NMR to DFT-computed spectra. DFT calculations of the transition-state structures corroborate experimentally observed stereoselectivity and identify key stabilizing and destabilizing interactions between the chiral ligand and allene-yne PKR substrates. The robust nature of our catalyst-ligand system places the total synthesis of thapsigargin and its stereoisomeric analogues within reach.

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Chirality: a key parameter in chemical probes

Abstract: Many small molecule bioactive and marketed drugs are chiral. They are often synthesised from commercially available chiral building blocks. However, chirality is sometimes incorrectly assigned by manufacturers with consequences for...

Cited by 4 publications

References 24 publications

Conformational and Chiroptical Properties of Salicylamide-Based Peptidomimetics

Conformational and Chiroptical Properties of Salicylamide-Based Peptidomimetics

Facile Synthesis of a Lipid-compatible, Dual-functionalised, and Enantiospecific Photoactivatable Linker

Stereo-Differentiating Asymmetric Rh(I)-Catalyzed Pauson–Khand Reaction: A DFT-Informed Approach to Thapsigargin Stereoisomers

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