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Synthetic Studies toward Galbulimima Alkaloid (−)‐GB 13 and (+)‐GB 16 and (−)‐Himgaline
Author(s) -
Zi Weiwei,
Yu Shouyun,
Ma Dawei
Publication year - 2011
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201000556
Subject(s) - chemistry , enone , bicyclic molecule , moiety , intramolecular force , swern oxidation , trifluoroacetic acid , hemiaminal , aldol condensation , alkylation , stereochemistry , cyclohexanone , tetrahydrofuran , michael reaction , aldol reaction , ketone , enol , lactone , total synthesis , organic chemistry , catalysis , dimethyl sulfoxide , solvent
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.