Synthesis of Coleon B Tetra-o-methyl Ether

Abstract

Coleon B (1a), described by Eugster¹ in 1969, proved to be an exceptional member of the coleons with the extended conjugation reaching into the C.19 nor ring A. Using simple models, available from methyl O-methyl podocarpate (2a) we explored methods to introduce the proper C.2 to C.7 functionalities. The known² hydro-demethoxycarbonylation of the α,β-unsaturated ketone 3a in the presence of 3-quinuclidinol which affords the enone 4 gave us a model for placing a C.3 — C.4 double bond which was realized by treatment of 4 with N-bromosuccinimide. The presumed C.4 bromo intermediate spontaneously eliminated hydrogen bromide to extend the conjugation to give 5a (H nmr : 1.38 (s, CH₃C.10), 1.98 (fine m, CH₃C.4), 3.90 (s, CH₃O), 6.07 (m, H-3), 6.39 (s, H-C.6) δ). The Ratcliffe-Rodehorst reagent oxidised the allylic methylene group to give a useful yield of the diene-dione 6a (H nmr : 1.53 (s, CH₃C.10), 2.27 (d, J=1.2 Hz, CH₃C.4), AB q. centred at 2.92 (J=16 Hz, H₂C.1), 3.93 (s, CH₃O), 6.24 (br. s, H-C.3), 6.73 (s, H-C.6) δ) which has similar but not identical functionality to coleon B.