The drimentines are a family of nine alkaloids isolated from two <i>Actinomycete</i> strains. Preliminary assays of their biological activity found weak to moderate cytotoxic and antibacterial activities. Despite these modest biological activities, the drimentines are intriguing because they contain a fusion of motifs commonly found in drug candidates including pyrroloindoline, sesquiterpene, and diketopiperazine moieties. Therefore, since their modes of action remain unknown, the drimentines are of interest for further study. This work focuses on a concise total synthesis of the drimentines in order to provide material for further assays of biological activity.<br/><br/>The drimentine core will be convergently synthesized from the pyrroloindoline and sesquiterpene subunits. Oxidative cyclization of L-tryptophan provides the pyrroloindoline moiety. Lactone ring-opening of (+)-sclareolide followed by alcohol elimination to form the exocyclic olefin affords the sesquiterpene fragment. The union of these two subunits via C–C bond formation requires the development of new chemistry. To that end, model studies on the combination of the alkaloid and sesquiterpene fragments will be presented. Late stage installation of the diketopiperazine ring from the corresponding amino acids would allow for the synthesis of multiple members, as this is the drimentine family’s point of divergence. Overall, the synthesis of the sesquiterpene and pyrroloindoline fragments, as well as studies toward their productive union will be discussed.

Studies into the total synthesis of the drimentine alkaloids

249th National Meeting (2015)

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