Modular synthesis of the pentacyclic core of batrachotoxin and select batrachotoxin analogue designs

Abstract

Pentacyclic analogues of the potent voltage-gated sodium ion channel agonist batrachotoxin can be accessed through an intermediate furan by exploiting Diels–Alder cycloaddition reactions with ring-strained dienophiles. The use of 3-bromofuran as a 1,2-dianion equivalent, the application of carbamate reductive N-alkylation for homomorpholine ring assembly, and the demonstration of CsF as an effective reagent for generating benzyne, cyclohexyne, and related dienophiles underscore this work.