Synthesis of naturally occurring bioactive butyrolactones: maculalactones A–C and nostoclide I

Starting from citraconic anhydride (), a simple multistep (9–10 steps) synthesis of naturally occurring butyrolactones maculalactone A (), maculalactone B (), maculalactone C () and nostoclide I () have been described with good overall yields via dibenzylmaleic anhydride () and benzylisopropylmaleic anhydride (). The two anhydrides and were prepared by SN2′ coupling reactions of appropriate Grignard reagents with dimethyl bromomethylfumarate (), LiOH-induced hydrolysis of esters to acids, bromination of carbon–carbon double bond, in situ dehydration followed by dehydrobromination and chemoselective allylic substitution of bromoatom in disubstituted anhydrides and with appropriate Grignard reagents. The NaBH4 reduction of these anhydrides and furnished the desired lactones and , respectively. The lactone on Knoevenagel condensation with benzaldehyde, furnished maculalactone B (), which on isomerization gave maculalactone C (). Selective catalytic hydrogenation of gave maculalactone A (). The conversion of lactone to nostoclide I () is known.