Efficient assembly of the phomactin core via two different macrocyclization protocols.
[reaction--see text] The core structure of phomactins C and D was assembled by an efficient strategy starting from 3,4-dimethylcyclohexen-2-one. Key reactions include (1) a high yielding and highly diastereoselective Michael addition of a mixed cuprate, (2) a carbonylative alkyne-enoltriflate coupling or an intramolecular addition of an acetylide onto an aldehyde to form the macrocycle, (3) chemoselective Michael addition of a cuprate to an enynone, to give the carbon framework of desformyl phomactin C or D, and finally (4) regioselective addition of a thia-nucleophile to the more reactive beta-position of the resulting dienone.
Houghton
T J
TJ
Chemistry Department, University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA.
Choi
S
S
Rawal
V H
VH
D018360:Crystallography, X-Ray; D003500:Cyclization; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
D004852:Epoxy Compounds; D006575:Heterocyclic Compounds, 3-Ring; D007202:Indicators and Reagents; D010972:Platelet Activating Factor; C438975:phomactin C; C103093:phomactin D