Formal Synthesis of (-)-Quinagolide: Diastereoselective Ring Expansion via a Bicyclic Aziridinium Ion Strategy to Access the Octahydrobenzo[g]quinoline Architecture.

Abstract

The diastereoselective formal synthesis of (-)-quinagolide, a D2 receptor agonist, has been achieved. The synthesis started from l-pyroglutamic acid and relied on utilization of (a) a stereospecific catalytic hydrogenation and diastereoselective Horner-Emmons-Michael cascade to obtain functionalized prolinate, (b) a Lewis acid mediated Pummerer cyclization to construct a tricyclic fused ring system, and (c) a diastereoselective ring expansion via a bicyclic aziridinium intermediate to access the required 3-substituted piperidine scaffold.