Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor Intermediates
Using methods of DFT, we investigated the effect of electron withdrawing and electron donating groups on the relative stability of tentative glycosyl donor reaction intermediates. The calculation shows that by changing the stereoelectronic properties of the protecting group, we can influence the sta...
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MDPI AG
2025-01-01
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| Series: | Molecules |
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| author | Ryan W. Kwok Ryan Rutkoski Pavel Nagorny Mateusz Marianski |
| author_facet | Ryan W. Kwok Ryan Rutkoski Pavel Nagorny Mateusz Marianski |
| author_sort | Ryan W. Kwok |
| collection | DOAJ |
| description | Using methods of DFT, we investigated the effect of electron withdrawing and electron donating groups on the relative stability of tentative glycosyl donor reaction intermediates. The calculation shows that by changing the stereoelectronic properties of the protecting group, we can influence the stability of the dioxolenium type of intermediates by up to 10 kcal mol<sup>−1</sup>, and that by increasing nucleophillicity of the 4-<i>O</i>-Bz group, the dioxolenium intermediate becomes more stable than a triflate–donor pair. We exploited this mechanism to design galactosyl donors with custom protecting groups on O2 and O4, and investigated the outcome of the reaction with cyclohexanol. The reaction showed no change in the product distribution, which suggests that the neighboring group participation takes precedence over remote group participation due to kinetic barriers. |
| format | Article |
| id | doaj-art-6d8734e01ddd4a098363c66e87dd6b5d |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-6d8734e01ddd4a098363c66e87dd6b5d2025-01-24T13:43:09ZengMDPI AGMolecules1420-30492025-01-0130221810.3390/molecules30020218Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor IntermediatesRyan W. Kwok0Ryan Rutkoski1Pavel Nagorny2Mateusz Marianski3Department of Chemistry, Hunter College, The City University of New York, 695 Park Ave., New York, NY 10065, USADepartment of Chemistry, University of Michigan, 930 University Ave., Ann Arbor, MI 48109, USADepartment of Chemistry, University of Michigan, 930 University Ave., Ann Arbor, MI 48109, USADepartment of Chemistry, Hunter College, The City University of New York, 695 Park Ave., New York, NY 10065, USAUsing methods of DFT, we investigated the effect of electron withdrawing and electron donating groups on the relative stability of tentative glycosyl donor reaction intermediates. The calculation shows that by changing the stereoelectronic properties of the protecting group, we can influence the stability of the dioxolenium type of intermediates by up to 10 kcal mol<sup>−1</sup>, and that by increasing nucleophillicity of the 4-<i>O</i>-Bz group, the dioxolenium intermediate becomes more stable than a triflate–donor pair. We exploited this mechanism to design galactosyl donors with custom protecting groups on O2 and O4, and investigated the outcome of the reaction with cyclohexanol. The reaction showed no change in the product distribution, which suggests that the neighboring group participation takes precedence over remote group participation due to kinetic barriers.https://www.mdpi.com/1420-3049/30/2/218glycosylation mechanismDFTremote participation |
| spellingShingle | Ryan W. Kwok Ryan Rutkoski Pavel Nagorny Mateusz Marianski Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor Intermediates Molecules glycosylation mechanism DFT remote participation |
| title | Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor Intermediates |
| title_full | Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor Intermediates |
| title_fullStr | Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor Intermediates |
| title_full_unstemmed | Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor Intermediates |
| title_short | Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor Intermediates |
| title_sort | stereoelectronic effect of protecting groups on the stability of galactosyl donor intermediates |
| topic | glycosylation mechanism DFT remote participation |
| url | https://www.mdpi.com/1420-3049/30/2/218 |
| work_keys_str_mv | AT ryanwkwok stereoelectroniceffectofprotectinggroupsonthestabilityofgalactosyldonorintermediates AT ryanrutkoski stereoelectroniceffectofprotectinggroupsonthestabilityofgalactosyldonorintermediates AT pavelnagorny stereoelectroniceffectofprotectinggroupsonthestabilityofgalactosyldonorintermediates AT mateuszmarianski stereoelectroniceffectofprotectinggroupsonthestabilityofgalactosyldonorintermediates |