Studies relating to fecapentaene-12

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Virginia Polytechnic Institute and State University

The glyceryl enol ether fecapentaene-12 (FP-12) is a direct-acting mutagen that is formed by bacteria in the lower part of the gastrointestinal tract from a precursor of unknown structure. Two major unsolved questions concerning FP-12 are the structure of its precursor and the nature of its interaction (if any) with DNA.

The structure of the biosynthetic precursor of FP-12 is thought to be that of a plasmalogen with an intact pentaenyl ether moiety. A synthesis of the perhydro analog of the proposed precursor structure is described, and approaches to the synthesis of the precursor itself are also described. Comparison of chromatographic data for the saturated model precursor and natural precursor provided evidence for the structure of the latter.

The nature of the interactions of FP-12 with DNA was probed by model studies of the reaction of nucleoside bases with FP-12 and two proposed FP-12 metabolites. No adducts were formed between FP-12 or between the various putative polyenal metabolites and guanosine, cytosine, or thymidine. A model epoxy ether did react with a guanosine derivative, however, indicating that an epoxy ether derivative of FP-12, if formed, would be capable of reacting with DNA.