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.