Cyclohexyne cycloinsertion in the divergent synthesis of guanacastepenes.
The guanacastepenes are a family of 15 diterpenes that share a common 5-6-7 tricyclic core, which is decorated with quaternary centers, unsaturation, hydroxyl and carbonyl groups. Some of these natural products show interesting antimicrobial potency. Their collective structural and biological features have stirred up vibrant activity among organic chemists. Herein, we disclose an account of our studies toward the synthesis of a number of guanacastepenes. The synthetic strategy relies on the use of cyclohexyne in a cycloinsertion reaction to rapidly construct the guanacastepene core. Isolation of a cyclobutenol as intermediate in the cyclohexyne cycloinsertion provided us with the possibility to study further the reactivity of this metastable compound, and we uncovered novel rearrangements and ring-opening reactions. Stereoselective, late-stage oxidative diversification of the carbon scaffold allowed the synthesis of guanacastepenes N and O and paved the way for the synthesis of guanacastepenes H and D.
Laboratorium für Organische Chemie, ETH Zürich, Switzerland.
Christian M
CM
Gampe
Erick M
EM
Carreira
D003503:Cyclobutanes / Q000737:chemistry*; D003510:Cyclohexanes / Q000737:chemistry*; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D003503:Cyclobutanes; D003510:Cyclohexanes; D004224:Diterpenes; C538814:cyclobutanol; C409194:guanacastepene