Divergent Syntheses of (-)-Chicanine, (+)-Fragransin A2, (+)-Galbelgin, (+)-Talaumidin, and (+)-Galbacin via One-Pot Homologative γ-Butyrolactonization.

In this study, the divergent syntheses of (-)-chicanine, (+)-fragransin A2, (+)-galbelgin, (+)-talaumidin, and (+)-galbacin are detailed. In this approach, an early-stage modified Kowalski one-carbon homologation reaction is utilized to construct the central γ-butyrolactone framework with the two necessary ß,γ-vicinal stereogenic centers. The two common chiral γ-butyrolactone intermediates were designed to be capable for assembling five different optically active tetrahydrofuran lignans from commercially available materials in a concise and effective divergent manner in five to eight steps. These five syntheses are among the shortest and highest-yielding syntheses reported to date.

Total Synthesis of Gymnothelignan K via a One-Pot Homologative γ-Butyrolactonization.

The first total synthesis of tetrahydrofuran dilignan gymnothelignan K is disclosed. The approach is based on implementing an early stage one-carbon homologative lactonization, which we recently disclosed, for constructing the γ-butyrolactone scaffold with the requisite ß,γ-trans-vicinal stereocenters. Other salient features of the synthesis include the acid-promoted dimerization and the Suzuki-Miyaura cross-coupling reaction to install the challenging diaryl skeleton that permits the effective assembly of the optically active gymnothelignan K in 8 steps from commercially available materials.

Divergent Total Syntheses of Gymnothelignan N, Beilschmin A, and Eupomatilones 1, 3, 4, and 7.

A seven-step asymmetric total synthesis of gymnothelignan N is detailed in the current report. The approach is based on an early-stage one-carbon homologative lactonization reaction, which we recently revisited and modified to construct the core γ-butyrolactone motif with the requisite ß,γ-vicinal stereogenic centers. By design, the utilization of the same chiral γ-butyrolactone intermediate permitted the rapid and effective divergent assembly of optically active eupomatilones 1, 3, 4, and 7 in five or six steps from commercially available materials. This represents one of the shortest and highest-yielding syntheses reported to date.