New approach to aphidicolin and total asymmetric synthesis of unnatural (11R)-(-)-8-epi-11-hydroxyaphidicolin by tandem transannular Diels-Alder/aldol reactions.
The 8-epiaphidicolane skeleton (3) was formed in one key reaction by highly diastereoselective tandem transannular Diels-Alder (TADA)-aldol reactions from the trans-trans-cis trienic macrocycle (4). The unnatural derivative (11R)-(-)-8-epi-11-hydroxyaphidicolin (2) was thus constructed, and an original solution to the C16 functionalization problem of many aphidicolin (1) syntheses is presented.
Bélanger
G
G
Laboratoire de synthèse organique, Département de chimie, Institut de Pharmacologie, Université de Sherbrooke, Fleurimont, Québec, Canada J1H 5N4.
Deslongchamps
P
P
D000447:Aldehydes; D016590:Aphidicolin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D015394:Molecular Structure
D000447:Aldehydes; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D016590:Aphidicolin