The Tandem Ring Opening/Ring Closing Metathesis Route to Oxaspirocycles: An Approach to Phelligridin G

Harold Cooper,Dennis Wright

doi:10.3390/molecules18022438

Abstract

Phelligridin G is an unusual natural product that contains an embedded spiro-fused furanone core. We have investigated two furan-based synthetic approaches towards the spirocyclic core structure of this natural product from readily available 2-phenylfurans. Although initial studies involving an oxidative cyclization were unsuccessful, we were ultimately able to access this key system through a sequential intermolecular furan Diels-Alder reaction followed by a metathesis-based reorganization. A related approach led to an expanded C ring to form spiro-fused pyran spirocycles.

Highlights

There are a variety of therapeutics in use today that are derived from natural products isolated from various plant, marine or microbial sources
Phelligridins D, E and G (Figure 1) are interesting natural products isolated from the fruiting body of P. igniarius
Diels-Alder reaction to give 3, followed by a ring opening metathesis/ring closing metathesis (ROM/RCM) process could deliver the target intermediate, a strategy we have recently employed in an approach to cyclopamine [8]

Summary

Introduction

There are a variety of therapeutics in use today that are derived from natural products isolated from various plant, marine or microbial sources. There is increasing evidence from animal studies that regular administration of powdered medicinal mushrooms can produce anti-cancer effects, demonstrating both high antitumor activity and restriction of tumor metastasis [1]. One such family of medicinal fungi has been derived from the species Phellinus igniarius, a member of the Polyporaceae family. Diels-Alder reaction to give 3, followed by a ring opening metathesis/ring closing metathesis (ROM/RCM) process could deliver the target intermediate, a strategy we have recently employed in an approach to cyclopamine [8].

Electrochemical Studies

Experimental

Conclusions