Biomimetic Synthesis of the Tetracyclic Core of Berkelic Acid

Acid-catalyzed condensation of 2,6-dihydroxybenzoic acid 3 with ketal aldehyde 14 in methanol at 25 °C, followed by CH2N2 esterification, gave a 4:1:4:1 mixture of diastereomers 15b−18b in 60% yield. Equilibration of this mixture with TFA in CDCl3 provided tetracycle 15b (83% yield) with the complete skeleton of berkelic acid. A similar condensation at 0 °C afforded 15b−18b and a reduction product 19b, which was probably formed by a 1,5-hydride shift.