Synthetic studies on the medicinally useful compounds through radical cyclization and olefin metthesis

Abstract

Studies aimed at the synthesis of spiropiperidines and spiropyrrolidines have been performed. Spiropiperidines are the key structure of some growth hormone secretagogues. Our first scheme to spiropiperidines using Grignard reagent or organocuprate reagents was not successful. Also treatments of α, β-unsaturated ketone 8 in various Nazarov cyclization conditions did not succeed. 5-exo-Trig intramolecular cyclizaiton of an aryl radical to the 4-position of a piperidine such as 13 would provide spiropiperidine 5. Spiropyrrolidine 23 was synthesized from methallyl alcohol in five steps. This synthetic route includes ruthenium catalyzed ring-closing metathesis. For the synthesis of dipeptide isostere containing cis-epoxide 26 which is the key component of LB-7116, intermediate 32 has been synthesized from L-phenylalanine in nine steps. Epoxidation of 31-33 is in progress.