Polyunsaturated C-Glycosidic 4-Hydroxy-2-pyrone Derivatives: Total Synthesis Shows that Putative Orevactaene Is Likely Identical with Epipyrone A

Angewandte Chemie - International Edition

5 years ago

Polyunsaturated C-Glycosidic 4-Hydroxy-2-pyrone Derivatives: Total Synthesis Shows that Putative Orevactaene Is Likely Identical with Epipyrone A

Saskia Schulthoff, Julia Lingnau, Conny Wirtz, Alois Fürstner, Johannes Preindl

Orevactaene and epipyrone A were previously thought to comprise the same polyunsaturated tail but notably different C-glycosylated 4-hydroxy-2-pyrone head groups. Total synthesis now shows that the signature bicyclic framework assigned to orevactaene is a chimera; the compound is almost certainly identical with epipyrone A, whose previously unknown stereochemistry has also been established during this study. Key to success was the ready formation of the bicyclic core of putative orevactaene by a sequence of two alkyne cycloisomerization reactions using tungsten and gold catalysis. Equally important was the flexibility in the assembly process gained by the use of heterobimetallic polyunsaturated modules whose termini could be selectively and consecutively addressed in a practical one-pot cross-coupling sequence. The wrong head: Synthesis shows that the proposed structure of orevactaene is a chimera; rather than comprising a head group in which the sugar is annulated to a 2-pyrone, the compound is a regular β-C-glycoside and hence most likely identical with epipyrone A. A tungsten-catalyzed glycal formation, a gold-catalyzed pyrone cyclization, and a stitching assembly process using a heterobimetallic linchpin were key for solving the riddle.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201702189