The Total Synthesis of Haplomyrtin

Abstract

<p>Haplomyrtin, a 1-aryl-2-3-naphthalide lignan obtained from Turkish Haplophyllum myrtifolium offers a number of synthetic challenges with the incorporation of two aromatic hydroxyl groups at positions 4 and 7 on the naphthalene ring system and regiospecific condensation of the v-lactone ring. The total synthesis of haplomyrtin is currently being pursued with commercially available vanillin and piperonal in a total of 10 separate steps. All steps have excellent reproducibility with good yields. This strategy includes halogenations of protected vanillin and incorporation of the fully functionalized pendant aryl ring through a lithium-halogen exchange followed by coupling with piperonal. The C-4 hydroxyl group is placed by the in-situ formation of a benzofuran subsequent DielsAlder reaction with dimethyl acetylenedicarboxylate (DMAD), deprotection and regiospecific reduction of the 0hydroxyester followed by transesterification to close the g-Iactam ring. Investigating the use of 4-methoxy benzyl bromide instead of benzyl chloride as a protecting group, addressing the instability of the secondary alcohol from the coupling reaction with piperonal as well as the poor yields and difficult isolation of the DielsAlder reaction product, and completions of haplomyrtin with improvements to the overall yields are the goals of this project.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>