Total Synthesis and Structural Elucidation of (−)-Cephalezomine G

Abstract

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.

Proline Ester Enolate Claisen Rearrangement and Formal Total Synthesis of (−)-Cephalotaxine

“…[α] D 22 = −196.7 ( c 1.0, CHCl 3 ) for 97 ee%}. In addition, the spectral data of 26 , obtained by dihydroxylation of I with OsO 4 , closely matched those reported by Mori . Thus, we have achieved the formal asymmetric synthesis of (−)-cephalotaxine ( 1 ).…”

Stereoselective Gold(I)‐Catalyzed Vinylcyclopropanation via Generation of a Sulfur‐Substituted Vinyl Carbene Equivalent

“…We thus performed the reported dihydroxylation step on the mixture of positional alkene isomers, which allowed us to isolate Moris known diol precursor 60, completing the formal synthesis. [11] Interestingly, the diol 60 also has been previously proposed, [12] but recently revised, [13] as the structure of the related natural product cephalezomine G, whose erroneous structural assignment is again confirmed by this work.…”

Stereoselective Gold(I)‐Catalyzed Vinylcyclopropanation via Generation of a Sulfur‐Substituted Vinyl Carbene Equivalent

“…We thus performed the reported dihydroxylation step on the mixture of positional alkene isomers, which allowed us to isolate Mori's known diol precursor 60 , completing the formal synthesis [11] . Interestingly, the diol 60 also has been previously proposed, [12] but recently revised, [13] as the structure of the related natural product cephalezomine G, whose erroneous structural assignment is again confirmed by this work.…”