Enantioselective total synthesis of the potent antitumor agent (-)-mucocin using a temporary silicon-tethered ring-closing metathesis cross-coupling reaction.
The enantioselective total synthesis of the annonaceous acetogenin (-)-mucocin (1) was accomplished using a triply convergent 12-step sequence (longest linear sequence) in 13.6% overall yield. This represents the first application of the temporary silicon-tethered (TST) ring-closing metathesis (RCM) cross-coupling reaction and the enantioselective alkyne/aldehyde addition to the synthesis of a complex annonaceous acetogenin. Moreover, all three fragments required for the coupling reactions are conveniently prepared in 5-6 steps from two readily available enantiomerically enriched epoxides. Finally, this synthesis stimulated the development of a new approach for the construction of 3-hydroxy-2,6-disubstituted tetrahydropyrans, using the bismuth tribromide-mediated reductive etherification reaction, which represents a motif that is prevalent in a wide range of pharmacologically significant natural products.
Evans
P Andrew
PA
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Cui
Jian
J
Gharpure
Santosh J
SJ
Polosukhin
Alexei
A
Zhang
Hai-Ren
HR
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D003500:Cyclization; D007783:Lactones / Q000138:chemical synthesis*; D011714:Pyrans / Q000138:chemical synthesis*; D031045:Rollinia / Q000737:chemistry; D012825:Silicon / Q000737:chemistry; D013237:Stereoisomerism
D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D011714:Pyrans; C413144:mucocin; D012825:Silicon