Toward the synthesis of sclerophytin A

by Dormi, Silvana S.; Hutchison, John M.; Lindsay, Harriet A.; McIntosh, Matthias C.

Sclerophytin A is eunicellin diterpene cytotoxic against the L1210 leukemia cell line. Our synthetic route employs an Ireland-Claisen rearrangement of a bis-allylic ester to install the C7 stereocenter. The pentadienoic acid product of the rearrangement was prepared in 5 steps from (S)-(&)-carvone and lacks only the C2-C5 carbons. Following a diastereoselective Ag(I)-mediated syn SN2' lactonization of the dienic acid, a novel Cu(I)-mediated anti SN2' addition of an alkoxymethyl nucleophile was used to install the C1-C2 bond. The furan ring was accessed by a base-promoted cyclization of the C9 oxygen. Subsequent installation of the C10 stereocenter was achieved via an allylic diazene rearrangement. Further progress toward the target will be presented.