Synthesis of Spiroketals Related to Griseusin A

Abstract

The synthesis and attempted functionalization of the spiroketal ring system of the naturally occurring pyranonaphthoquinone antibiotic griseusin A 1 is reported. The unsaturated spiroketals 5,6 were prepared from furonaphthopyran 22, which in turn was constructed from furonaphthofuran 20. Addition of 2-trimethylsilyloxyfuran 13 to quinone 19 afforded furonaphthofuran 20. Initial work using acetylenic quinone 12 afforded a pentacyclic product 15, where a third Michael reaction of the phenolic hydroxyl group with the α,β-unsaturated ketone moiety had occurred. Modified reaction conditions afforded trimethylsilyl analogue 16. Naphthoquinone 19, which bears a 2-alkenyl side chain rather than an acetylene, was synthesized using similar methodology to 12 and subsequently converted to furonaphthofuran adduct 20. Ceric ammonium nitrate oxidative rearrangement of 20 produced diol 22, which was then cyclized to spiroketals 5,6 under acidic conditions. Reaction of spiroacetals 5,6 with osmium tetroxide did not effect the desired hydroxylation of the olefin. Use of cetyltrimethylammonium permanganate as the hydroxylation reagent resulted in reaction with the C5a-C11a double bond affording diols 24,25.