Studies on the total synthesis of daphnane diterpene orthoesters
Embargo Date
2019-11-27
OA Version
Citation
Abstract
Disclosed herein are comprehensive details of a study on the total chemical synthesis of daphnane diterpene orthoesters (DDOs), a large group of secondary metabolites isolated from the plant families Eurphorbiacaea and Thymelaeaceae which are known to possess a broad spectrum of powerful biological activities.
Characterized by a tricyclo[9.3.0.0]tetradecane core ring system with two trans-fused ring junctures, an average of nine oxygen appendages, and an unusual orthoester functionality, DDOs are amongst the most complex and structurally varied diterpene natural products and present a significant challenge towards de novo chemical synthesis.
These studies culminated in short (10-12 steps from known starting materials, 16-18 total operations), stereocontrolled syntheses of tricyclic DDO cores containing seven contiguous stereocenters, of which six directly correspond to all known DDOs. Key to their assembly was the development of a concise p-quinol functionalization choreography that enabled rapid access to C-ring stereopolyads from simple precursors. Efforts to apply this strategy to the total synthesis of (±)-resiniferatoxin (RTX) are described in addition to a discussion for future work from this laboratory.