Total synthesis of (+)-intricarene using a biogenetically patterned pathway from (-)-bipinnatin J, involving a novel transannular [5+2] (1,3-dipolar) cycloaddition.
An asymmetric synthesis of the furanobutenolide-based macrocyclic diterpene (-)-bipinnatin J (4a) isolated from the gorgonian octocoral Pseudopterogorgonia bipinnata is described. The synthesis is based on elaboration of the chiral lactone-substituted vinyl iodide 26b from (+)-glycidol, followed by an intermolecular Stille coupling reaction with the stannylfurfural 27, leading to 28a, and then an intramolecular Nozaki-Hiyama-Kishi allylation reaction, 28b --> 4a. Treatment of (-)-bipinnatin J (4a) with VO(acac)2-tBuO2H followed by acetylation of the tautomeric hydroxypyranone product 7/8, next gave the acetoxypyrone 30. When the acetoxypyranone 30 was heated in acetonitrile in the presence of DBU, it gave (+)-intricarene 1, which is found in P. kallos, via a novel transannular [5+2] (or 1,3-dipolar) cycloaddition involving the butenolide-oxidopyrylium ion intermediate 31. We believe that this total synthesis of (+)-intricarene 1 mimics its most likely origin in nature via oxidation of (-)-bipinnatin J (4a), presumably involving photochemically generated singlet oxygen or possibly a P450 monooxygenase enzyme system.
Tang
Bencan
B
School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Bray
Christopher D
CD
Pattenden
Gerald
G
D032701:Biomimetics; D004224:Diterpenes / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism
D004224:Diterpenes; D014315:Triterpenes; C513883:bipinnatin J; C507581:intricarene