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8721852 
Journal Article 
Cyclohexyne cycloinsertion in the divergent synthesis of guanacastepenes 
Gampe, CM; Carreira, EM 
2012 
Yes 
Chemistry: A European Journal
ISSN: 0947-6539
EISSN: 1521-3765 
18 
49 
15761-15771 
English 
23080228 
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. No strain, no gain! Studies toward the synthesis of the guanacastepene family of diterpenes are presented. The synthetic strategy relies on the use of cyclohexyne as the guanacastepene C-ring, which undergoes cycloinsertion to form the tricyclic carbon scaffold. A host of procedures developed for the diversification of the carbon core allowed the synthesis of guanacastepenes N and O and paved the way for the synthesis of guanacastepenes D and H. Copyright 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 
cyclohexyne; cycloinsertion; guanacastepene; natural products; total synthesis