On the Origin of Siphonariid Polypropionates: Total Synthesis of Baconipyrone A, Baconipyrone C, and Siphonarin B via their Putative Common Precursor

摘要

Abstract: The hypothesis that siphonariid polypropionates originate from nonenzymatic processes on acyclicnbiosynthetic precursors was tested by examining the properties of the putative common precursor for thenS. zelandica decapropionates siphonarin B, caloundrin B, baconipyrone A, and baconipyrone C, i.e.,n(4S,5S,6S,8RS,10S,11S,12R,14R)-14-(6-ethyl-3,5-dimethyl-4-oxo-4H-pyran-2-yl)-5,11-dihydroxy-n4,6,8,10,12-pentamethylpentadecane-3,7,9,13-tetraone. The first synthesis of such a precursor was achievednin an efficient and fully enantioselective manner using a thiopyran-based strategy for polypropionatensynthesis. This putative precursor, a complex mixture of ring chain and keto enol tautomers, was kineticallynstable and isomerized exceedingly slowly to the thermodynamically more stable siphonarin B. In the presencenof imidazole, the mixture reached apparent equilibrium within several hours giving siphonarin B as thenpredominant component (ca. 70%), thereby constituting its enantioselective total synthesis. In the presencenof alumina, both siphonarin B and the dihydroxytetraone precursor underwent retro-Claisen rearrangementsn(via a hemiacetal tautomer) to give baconipyrones A and C among other products. This is the first totalnsynthesis of baconipyrone A and “biomimetic” synthesis of baconipyrone C. Control experiments suggestednthat baconipyrone A was produced in an unprecedented cascade process where the intermediate enol(ate)nof the retro-Claisen rearrangement was directly engaged in aldol cyclization while baconipyrone C resultednfrom simple ketonization of the enol(ate). These experiments provide the first unambiguous demonstrationnthat the baconipyrones are plausible isolation artifacts and suggest they are most likely derived fromnsiphonarins rather than an “acyclic” precursor. Caloundrin B was not detected among the products fromnany of the isomerization experiments, suggesting the possibility that it is an unstable biosynthetic product.