Asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol and zeaenol

Sai Reddy Doda,Chandra Shekar Putta,Sharath Babu Haridasyam,Sudhakar Kadari,Bhattu Kanakadurga Rao,Avula Raghavendar

doi:10.1515/hc-2019-0015

Abstract

AbstractAn efficient, short and, a convenient asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol (2) and zeaenol (1) have been achieved in 7 and 9 linear steps with the high overall yield of 32% and 21% respectively, from the known intermediate 13. Mitsunobu inversion, De Brabander’s protocol for macrolactonisation, Heck cross-coupling, diastereoselective alkyne aldehyde coupling and Ohira–Bestmann alkynylation are the key reactions.

Highlights

An efficient, short and, a convenient asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol (2) and zeaenol (1) have been achieved in 7 and 9 linear steps with the high overall yield of 32% and 21% respectively, from the known intermediate 13
The first total synthesis of zeaenol along with its analog cochliomycin A was reported by Nanda et al [8] using late stage ring closing metathesis (RCM) strategy
In continuation of our efforts on the total synthesis of biologically active lactonic natural products [14,15,16,17,18,19,20,21], we described a first asymmetric total synthesis of zeaenol and 7-epi-zeaenol

Summary

Introduction

Short and, a convenient asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol (2) and zeaenol (1) have been achieved in 7 and 9 linear steps with the high overall yield of 32% and 21% respectively, from the known intermediate 13. Introduction products zeaenol and 7-epi-zeaenol (Figure 1) are isolated by Oberlies and co-workers [4,5] from a filamentous fungus, MSX 63935, collected from the leaf litter in Nigeria, along with other natural products. These resorcylic acid lactones (RALs) exhibit potent antibacterial activity as well as mitochondrial transmembrane potential activity. Modern synthetic chemistry has enabled the identification, isolation, and manufacturing many of the promising biologically active filamentous fungi related natural products [1,2,3]. Doda et al.: Asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol 79

Findings

Discussion

Conclusion