抄録
Ophiodilactone A (1) and B (2), isolated from ophiuroid Ophiocoma scolopendrina, exhibit moderate cytotoxic activity against P388 murine leukemia cell with IC_<50> value of 5.0 and 2.2 μg/mL, respectivity. These compounds possess characteristic structures consisting of a fused γ-lactone/6-lactone skeleton with four or five contiguous stereogenic centers containg three quaternary centers and four phenyl groups. The absolute configuration of 1 was tentatively determined by its CD spectrum; however that of 2 has not been determined yet. Their unique highly substituted dilactone structures and intriguing biological activities prompt us to investigate the synthesis of ophiodilactones. Since ophiodilactone B (2) would be accessible from ophiodilactone A (1), we focused on the synthesis of 1 (Scheme 1). From a retrosynthetic perspective, we envisioned bicyclic ketone 5 as a precursor of 1. We expected that 1 would be obtained from 5 via construction of a dilactone core by Baeyer-Villiger oxidation and stereoselective introduction of benzyl and hydroxyl groups. To access 5 we selected the [2+2] cycloadditon of 6 as a key reaction. In this symposium, we will report a highly enantio- and stereoselective approach to ophiodilactone A (1). This approach involves organocatalytic asymmetric Micheal addition of dimethyl malonate to cinnamaldehyde, stereoselective formation of bicyclo [3.2.0] heptane 5e by [2+2] cycloaddition of ketene 19e, Baeyer-Villiger oxidation of cyclobutanone 20, and stereoselective introduction of benzyl and hydroxyl groups giving 26. Compound 26 was then converted to 27, a promising precursor of ophiodilactone A (1).
