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The first asymmetric synthesis and configurational elucidation of (-)-cephalezomine G was achieved. The highly functionalized Cα-substituted proline derivative was prepared from d-proline as the only chiral source via a C → N → C chirality transfer method consisting of stereoselective N-allylation and [2,3]-Stevens rearrangement. The azaspiranic tetracyclic backbone was constructed using ring-closing metathesis and the Friedel-Crafts reaction. Two contiguous hydroxyl groups were introduced in the later stages.

An efficient strategy for the asymmetric synthesis of Cα-tetrasubstituted proline derivatives from proline has been established. A nitrogen-fused bicyclic system was devised to control the stereodynamics of proline. Through N-quaternizations with allylic electrophiles followed by [2,3]-rearrangements, the bicyclic proline system delivered enantioenriched Cα-tetrasubstituted prolines. This strategy was applied to the concise total synthesis of (-)-amathaspiramide F.