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. 2024 May 15:104:129739.
doi: 10.1016/j.bmcl.2024.129739. Epub 2024 Apr 8.

Synthesis and antiproliferative activity of a tetrahydrofuran analog of FR901464

Ivanna Pohorilets  1 , Jacob P Beard  1 , Julia L Driscoll  1 , John C Schmitz  2 , Kazunori Koide  3
Affiliations

Synthesis and antiproliferative activity of a tetrahydrofuran analog of FR901464

Ivanna Pohorilets et al. Bioorg Med Chem Lett. .

Abstract

FR901464 is a natural product that exhibits antiproliferative activity at single-digit nanomolar concentrations in cancer cells. Its tetrahydropyran-spiroepoxide covalently binds the spliceosome. Through our medicinal chemistry campaign, we serendipitously discovered that a bromoetherification formed a tetrahydrofuran. The tetrahydrofuran analog was three orders of magnitude less potent than the corresponding tetrahydropyran analogs. This study shows the significance of the tetrahydropyran ring that presents the epoxide toward the spliceosome.

Keywords: Anticancer activity; Bromonium ion; Epoxide; RNA splicing; Tetrahydrofuran.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John C. Schmitz reports financial support was provided by UPMC Hillman Cancer Center NCI Cancer Center Support Grant Developmental Funds. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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