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 35through a diastereoselective hydrogenation. Mukaiyama–Michael addition of a bicyclic silyl enol ether to 35and subsequent stereochemistry inversion by means of an oxidation/reduction strategy provided lactone 41. After reduction of lactone 41with LAH, Swern oxidation was carried out to give enone 46upon a spontaneous intramolecular aldol reaction and cleavage of the ketal protecting group. SmI2‐mediated carbonyl–alkene reductive coupling of 46proceeded 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.