Synthetic studies toward galbulimima alkaloid (-)-GB 13 and (+)-GB 16 and (-)-himgaline.

Condensation of (S)-3-aminobutan-1-ol with 1,3-cyclohexane-dione followed by an intramolecular alkylation afforded bicyclic enamine 32, which was converted into enone 35 through a diastereoselective hydrogenation. Mukaiyama-Michael addition of a bicyclic silyl enol ether to 35 and subsequent stereochemistry inversion by means of an oxidation/reduction strategy provided lactone 41. After reduction of lactone 41 with LAH, Swern oxidation was carried out to give enone 46 upon a spontaneous intramolecular aldol reaction and cleavage of the ketal protecting group. SmI(2) -mediated carbonyl-alkene reductive coupling of 46 proceeded smoothly in refluxing tetrahydrofuran to deliver pentacyclic intermediate 49, which was oxidized with 2-iodoxybenzoic acid and then treated with trifluoroacetic acid to furnish (-)-GB 13. The overall yield was 6.1% over 19 linear steps. By following the known procedure, our synthetic (-)-GB 13 was converted into himgaline. In addition, by starting from lactone 41, the first total synthesis of (+)-GB 16, a newly isolated member of the gabulimima alkaloid family, was achieved. This synthesis features an intramolecular condensation between an amine and a 1,3-diketone moiety.