Total synthesis of antheliolide A.
The first synthesis of the structurally unique marine natural product antheliolide A (1) has been accomplished by the pathway outlined in Scheme 1. The sequence is stereocontrolled and has led to the synthesis of (+/-)-1, and ent-1 as well as 1. The route contains a number of noteworthy or novel steps including (1) formation of the mixed acetal 7, (2) the diastereoselective bicyclization to form 8 in which stereocenters are correctly established at each carbon of the four-membered ring, (3) the chain extension 8 --> 11, (4) the efficient closure of the nine-membered ring of 12, (5) the mild oxidative cleavage sequence 14 --> 17, and (6) the successful and quick formation of the last three rings of 1 from aldehyde 17 via 18. The synthesis of 1 has also resulted in the clarification of its absolute configuration, which had not been determined previously.
Mushti
Chandra Sekhar
CS
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Kim
Jae-Hun
JH
Corey
E J
EJ
D002851:Chromatography, High Pressure Liquid; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
D006571:Heterocyclic Compounds; D006576:Heterocyclic Compounds, 4 or More Rings; C522715:antheliolide A