FR901483: Synthetic Efficiency Remains a Challenge

FR901483 is a unique alkaloid bearing an aza-tricyclic structure, a phosphate group, and a congested tertiary nitrogen center. This alkaloid was reported to be a potent immunosuppressant with antimetabolite ability. The unprecedented architecture has captured imagination of synthetic chemists since its isolation in 1996. To date, ten total or formal syntheses and several synthetic approaches to access the tricyclic core skeleton have been reported. In this review, we highlight the novel synthetic methods and strategies and discuss the synthetic challenge for meeting the criteria of drug development. 1 Introduction 2 Bioinspired Total Synthesis of FR901483 3 Non-bioinspired Approaches toward FR901483 4 Various Tactics for Accessing the Core Skeleton 5 Challenges for Efficiency