Alkyne Cyclizations through Vinyl Cations and Stereoselective Allene Formation by Terpene Synthases.

An analog of the sesquiterpene precursor farnesyl pyrophosphate with the terminal double bond substituted by an alkyne functional group was synthesized and enzymatically converted with seven sesquiterpene synthases. In some cases, the alkyne function did not participate in the cyclization reaction, leading to alkyne analogs of known sesquiterpenes, but in other cases, the alkyne function was directly involved in the cyclization cascade, progressing through vinyl cations. The reactions yielded either terpenoid hydrocarbons or alcohols, or, if the vinyl cation was quenched by water or underwent deprotonation, ketones or allenes, respectively. Scabrisporallene isolated from a newly characterized δ-cadinene synthase from Embleya scabrispora contained an allene function embedded in a macrocyclic ring. A heating experiment revealed racemization of this compound at 120 °C with a half-life of about 24 h. Also, elongation of the FPP analog with one more isoprene unit by a geranylgeranyl pyrophosphate synthase and subsequent cyclization using a diterpene synthase proved to be possible. The absolute configurations of the isolated compounds and the cyclization mechanisms toward them were investigated through isotopic labeling experiments and through computational methods.