Advances Towards the Synthesis of Aporphine Alkaloids: C-Ring Formation via Approaches Based on One- and Two-Bond Disconnections

Abstract

Aporphine compounds constitute a class of substances with important pharmacological properties, including anticancer, antiviral, anti-HIV, anti-inflammatory, and leishmanicidal activities. Consequently, several strategies to obtain the aporphine core have been reported. Herein this review, we provide an overview of two relevant approaches used to construct the C-ring in the synthetic routes developed. The first approach, which is based on a one-bond disconnection, allows C-ring formation using a 1-benzyl-1,2,3,4-tetrahydroisoquinoline intermediate (mainly) employing cyclization reactions catalyzed by metals or promoted by light. The second approach, which is derived from a two-bond disconnection, leads to C-ring formation via a sequence of reactions starting with [4+2] cycloadditions. Through these approaches, aporphinoids with a diverse range of substitution patterns and biological activities can be synthesized.

Keywords: Alkaloids; benzyne chemistry; metal-catalyzed reactions; photochemical cyclizations; total synthesis.