Towards a Synthesis of Naphthalene Derived Natural Products

M Mcculloch,R Barrow

doi:10.3390/10101272

Abstract

Dieckmann-type cyclization reactions have been employed in the synthesis of the alkyl substituted naphthoquinone 11 and the naphthalenes 10 and 12. Various conditions for the benzylic oxidation of these compounds have been investigated with a view towards the synthesis of some naphthalene based natural products.

Highlights

A large number of naphthalene derived natural products are based on a substituted naphthalene skeleton as represented by 1
Given that 3 is the only linear NGP based natural product to have been synthesized, [5,6,7] and that many structurally related NGPs possessing biological properties have been isolated, we are interested in developing a general synthesis of NGPs and as a corollary this synthesis should be extendable to related naphthalene derived natural products represented here by 2 and 4
Shibata and co-workers circumvented this by cyclising the β-diketoester 5 at 200-220°C under high vacuum, [5] to give 1, albeit in a low 9% yield while some years later Rideout and colleagues increased the yield in the synthesis of 1 to 18% by cyclising 5 in refluxing 1-methylnaphthalene [8]

Summary

Introduction

A large number of naphthalene derived natural products are based on a substituted naphthalene skeleton as represented by 1. These include: the naphthyl ketone derivative guieranone A (2) [1], heterocyclic derivatives like the linear naphtho-γ-pyrone (NGP) rubrofusarin (3) [2,3], and naphthoquinones such as the crinoid derived pigment 4 [4]. Given that 3 is the only linear NGP based natural product to have been synthesized, [5,6,7] and that many structurally related NGPs possessing biological properties have been isolated, we are interested in developing a general synthesis of NGPs and as a corollary this synthesis should be extendable to related naphthalene derived natural products represented here by 2 and 4

OH O

OMe Me O OEt

MeO Br