Stereochemical Control of Splice Modulation in FD-895 Analogues.
In: Journal of medicinal chemistry, Jg. 66 (2023-05-25), Heft 10, S. 6577-6590
academicJournal
Zugriff:
Highly functionalized skeletons of macrolide natural products gain access to rare spatial arrangements of atoms, where changes in stereochemistry can have a profound impact on the structure and function. Spliceosome modulators present a unique consensus motif, with the majority targeting a key interface within the SF3B spliceosome complex. Our recent preparative-scale synthetic campaign of 17 S -FD-895 provided unique access to stereochemical analogues of this complex macrolide. Here, we report on the preparation and systematic activity evaluation of multiple FD-895 analogues. These studies examine the effects of modifications at specific stereocenters within the molecule and highlight future directions for medicinal chemical optimization of spliceosome modulators.
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Stereochemical Control of Splice Modulation in FD-895 Analogues.
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Autor/in / Beteiligte Person: | Chan, WC ; Trieger, KA ; La Clair, JJ ; Jamieson, CHM ; Burkart, MD |
Zeitschrift: | Journal of medicinal chemistry, Jg. 66 (2023-05-25), Heft 10, S. 6577-6590 |
Veröffentlichung: | Washington Dc : American Chemical Society ; <i>Original Publication</i>: [Easton, Pa.] : American Chemical Society, [c1963-, 2023 |
Medientyp: | academicJournal |
ISSN: | 1520-4804 (electronic) |
DOI: | 10.1021/acs.jmedchem.2c01893 |
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