Unified Divergent Total Synthesis of Discorhabdin B, H, K, and Aleutianamine via the Late-Stage Oxidative N,S-Acetal Formation

This study achieved the total syntheses of (+)-discorhabdin B, (-)-discorhabdin H, (+)-discorhabdin K, and (-)-aleutianamine. A phenethylamine fragment bearing a o-pivaloylthio group, corresponding to the D/E/G ring moiety, was prepared from benzothiophen-2-carboxylic acid methyl ester and condensed with a known pyrroloiminoquinone derivative. The adduct was subjected to [bis(trifluoroacetoxy)iodo]benzene (PIFA)-promoted oxidative spirocyclization to furnish the A/B/C/D/E spirocyclohexadienone fused with pyrroloiminoquinone. The total synthesis of (±)-discorhabdin B was completed via the key construction of the highly strained G ring with the N,S-acetal moiety featuring a newly developed CuBr2-mediated oxidative cascade cyclization. The stereocontrolled total synthesis of (+)-discorhabdin B was accomplished by a diastereoselective PIFA-promoted oxidative spirocyclization using a chiral thioester. (-)-Disocrhabdin H and (+)-discorhabdin K were synthesized by the site- and face-selective thia-Michael addition of l-ovothiol A to (+)-N-Ts-discorhabdin B with the concomitant formation of the F ring by forming the C2-N18 bond. The total synthesis of (-)-aleutianamine was achieved via a skeletal rearrangement initiated by the Luche reduction of the dienone moiety of (+)-N-Ts-discorhabdin B.