Total syntheses of (±)- and (-)-stemoamide

(+/-)-Stemoamide (1) was prepared in seven steps beginning with gamma-chlorobutryl chloride (20) and succinimide (15), which were efficiently converted to the key alkyne oxazole 17 on a multigram scale. Intramolecular (Diels-Alder)-(retro-Diels-Alder) reaction of 17 then gave butenolide 12b directly upon aqueous workup. The remaining two stereocenters in 1 were established In a single step by a highly selective reduction of 12b (NaBH4/NiCl2), followed by equilibration to the thermodynamically favored natural configuration. In analogous fashion (-)-stemoamide (1) was prepared beginning with L-pyroglutamic acid (S-35).