Modular enantioselective synthesis of 8-aza-prostaglandin E1.

We report herein for the first time the enantioselective synthesis of 8-aza-PGE1. The synthesis used the cross olefin metathesis reaction to connect the 5-vinyl-γ-lactam subunit, prepared from (R)-malic acid via the Ley's sulfone-based α-amidalkylation protocol (dr = 6.8:1), with the chiral pre-ω-chain. The latter was synthesized in high enantioselectivity from (E)-2-octenol by the Sharpless asymmetric epoxidation and the titanocene-mediated epoxide opening. This modular approach is quite concise and flexible, and requires only eight steps from commercially available reagents.