Obolactone

Definition

ChEBI: Obolactone is a pyranone isolated from the trunk barks of Cryptocarya obovata and has been shown to exhibit cytotoxicity against the KB cell line. It has a role as an antineoplastic agent and a plant metabolite. It is a member of 2-pyranones and a member of 4-pyranones.

Synthesis

The synthesis of (+)-obolactone (14, Scheme 3) by Brückner and Walleser employed the same conditions from the synthesis of 17-deoxyroflamycoin to transform bis-epoxide R,R-4 to bis-homoallylic diol S,S-8.  Diol 8 was then protected using 2,2-dimethoxypropane under acidic conditions to provide acetonide 12 in 95% yield. One of the alkene functional groups of the C2- symmetric acetal underwent a subsequent symmetry-breaking Wacker oxidation. Treatment of acetonide 12 with catalytic PdCl2 under an atmosphere of oxygen using CuCl as the stoichiometric oxidant afforded a 64% yield of methyl ketone 13, with over-oxidation to the diketone also observed (18% yield). The methyl ketone functionality of 13 was critical for the installation of the dihydro-g-pyranone moiety in the natural product, while the syn-orientation of the C–O bonds was achieved through Mitsunobu inversion of the lactone stereocenter. Brückner and Walleser specifically mention that while Krische and co-workers have reported on an impressive single-step procedure for the catalytic enantioselective synthesis of bishomoallylic diol (S,S-4) from 1,3-propanediol, and have used this method extensively in the synthesis of polyketide natural products, 21,22 the high cost of catalyst and ligand precluded their use on scale in this case.