Trigger appendage

Installation of the butenolide appendage was carried out by addition of the lithium anion of 4-methoxy-3-methyl-2(5//)furanone (241) to aldehyde 238 to provide a 2 1 mixture of diastereoisomeric alcohols 239, which was converted to a 2 1 mixture of diastereoisomeric ketones after Dess-Martin oxidation. Treatment of the respective ketones with trifiuoroacetic acid, followed by adjustment of the pH to 10, triggered a tandem triple cychzation to give stemofoline hydrate 240 in 67% yield. Dehydration of 240 proved surprisingly difficult due to the propensity for 240 to undergo retro-aldolization to provide pentacyclic lactone 242. Treatment of 240 with triflic anhydride provided a 12% yield of a single dehydration product (along with 24% of pentacyclic ketone 242) which proved to be identical by TLC and H-NMR spectroscopy with an authentic sample of natural isostemofoline. The synthetic sample was compared and shown to be identical to isostemofoline (224). 

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