Heterocyclic Prostaglandins. IV. Synthesis of 8-Aza-11-deoxyprostaglandin E₁ and Its Related Compounds

Abstract

Synthesis of 8-azaprostanoids (1a-e and 15a-e) from 5-hydroxymethyl-2-pyrrolidinone (3) was described. Acetylation of 3 and subsequent alkylation with methyl 7-iodoheptanoate yielded N-alkylated compound (7), which was converted into 5-hydro-xymethyl derivative (10) after selective hydrolysis. The same compound (10) was also conveniently prepared from 3 after ethoxyethylation and alkylation followed by treatment with acidic methanol. The Collins oxidation of 10 provided an aldehyde (11) which served as a key intermediate. The wittig reaction of 11 with various dimethyl 2-oxo-phosphonates yielded the corresponding enones (12a-e), which were reduced by sodium borohydride, followed by the separation of C₁₅-epimers and alkaline hydrolysis, to give moderate yields of 1a-e, and 15a-e.