RESEARCHES ON PROSTANOIDS. Ⅰ. TOTAL SYNTHESIS OF DL-PROSTAGLANDIN F2α AND ITS ω-ETHYL ANALOG

A simplified version of Corey's synthesis of the dl-PGF_2α and its ω-ethyl homolog wasreported. Diethyl 2-oxoheptylphosphonate (7A) and 2-oxononanylphosphonate (7B) were obtained through Arbuzov reaction in 70～80% yield by heating 1-bromoheptan-2-one and 1-bromononan-2-one respectively with triethylphosphite at 170～180 for 1 hr. Oxidation of 4-hydroxymethyl lactone (5) in mild acidic condition (DMSO, DCC in the presence of anhydrous H₃PO₄) furnished aldehyde (6), which was subjected to Wittig-Horner reaction with sodium salt of 7 in dichloromethane. Treatment of the resulting 8 with sodium borohydride in methanol yielded a ca. 1:1 mixture of 3'R and 3'S epimers 9. Treatment of 9 Aα and 9 Bα with an excess of diisobutyl aluminium hydride at -78° afforded the intermediates hemiacetal (10Aα)and (10Bα)in over 80% yield, which were further reacted with Wittig reagent derived from triphenylphosphonium pentanoic acid bromide in dimethylsulfoxide to give dl-PGF_2α (11A) and to-ethyl-dlPGF_2α (11B) in yields around 50%.