Total synthesis of grayanane natural products

Abstract

Grayananes are a broad family of diterpenoids found in Ericaceae plants, comprising more than 160 natural products. Most of them exhibit interesting biological activities, often representative of Ericaceae use in traditional medicine. Over the last 50 years, various strategies were described for the total synthesis of these diterpenoids. In this review, we survey the literature for synthetic approaches to access grayanane natural products. We will focus mainly on completed total syntheses, but will also mention unfinished synthetic efforts. This work aims at providing a critical perspective on grayanane synthesis, highlighting the advantages and downsides of each strategy, as well as the challenges remaining to be tackled.

Natural Product Synthesis: The Endless Quest for Unreachable Perfection

“…For example, in 1994, the group of Shirahama achieved the first enantioselective synthesis of grayanotoxin III in 38 steps and 0.05% overall yield, a real feat at the time (Scheme ). And 28 years later, the group of Luo reported the synthesis of the same molecule in only half the amount of steps and an overall yield 4 times higher (19 steps and 0.2% overall yield). , This spectacular improvement was made possible by multiple advances in organic chemistry, especially regarding asymmetric organocatalysis, cascade reactions, and transition-metal catalysis.…”