Synthetic studies toward the total synthesis of berkelic acid and lytophilippine A

Abstract

C16-C20 part of natural product berkelic acid containing two adjacent stereogenic centers has been synthesized employing catalytic asymmetric Gosteli-Claisen rearrangement of 2 alkoxycarbonyl-substituted allyl vinyl ether as a key step. Synthetic sequence leading to the both fragments included 11 linear steps and afforded final products in good to excellent diastereoselectivity and good enantioselectivity. Model study exploring Oxa-Pictet-Spengler condensation as a key coupling step toward the tetracyclic core of berkelic acid has been successfully accomplished.

C20-C27 fragment of lytophilippine A has been synthesized in a sequence of 13 linear steps, and in total yield of 8.4%. The synthesis commenced with readily available natural (+) L ascorbic acid and features Evans asymmetric alkylation and asymmetric aldol condensation with norephedrine-derived auxiliary as key steps to install the required C21-C23 anti, syn stereotriad.