Auto-oxidation of Ent -beyer-15-en-19-al isolated from the essential oil of the heartwood of Erythroxylum monogynum Roxb.: formation of 15,16-epoxy- ent -beyeran-19-oic acid and other products

Chemical investigation of the essential oil obtained from the heartwood of Erythroxylum monogynum Roxb. yielded three beyerene type diterpenoids ent -beyer-15-ene ( 1 ), ent -beyer-15-en-19-ol (erythroxylol A) ( 2 ) and ent -beyer-15-en-19-al ( 3 ). Ent -beyer-15-en-19-al ( 3 ) was found to be unstable at room temperature, giving rise to hitherto unknown 15,16-epoxy- ent -beyeran-19-oic acid ( 4 ). This conversion involves the auto-oxidation of a C-4 axial aldehyde group of an ent -beyer-15-ene diterpenoid with the concurrent epoxidation of the C-15 double bond. This is the first report of the auto-oxidation of an aldehyde group to a carboxylic acid group with the concurrent epoxidation of a double bond in the same compound. Further investigation of this observation under controlled conditions resulted in the isolation and identification of ent -beyer-15-en-19-oic acid ( 5 ), two new epoxy hydroperoxides, 15,16-epoxy-19- nor - ent -beyeran-4 α -hydroperoxide ( 6a ), 15,16-epoxy-18- nor - ent -beyeran-4 β -hydroperoxide ( 6b ), and two new hydroperoxides, ent -beyer-19- nor -15-en-4 α -hydroperoxide ( 7 ), ent -beyer-18- nor -15-en-4 β -hydroperoxide ( 8 ) and ent -beyer-18- nor -15-en-4 β -ol ( 9 ). Identification of these compounds was carried out by the extensive usage of spectroscopic data including 1D and 2D NMR. The acid 5 and the alcohol 9 have been reported previously as natural products from Elaeoselinum asclepium and Erythroxylum monogynum . The mechanistic basis of this auto-oxidation reaction is discussed.