Synthesis of naturally occurring quinones

ORGN 194

Aouregan M. Jacob, and Christopher J. Moody. University of Exeter, Stocker Road, EX4 4QD Exeter, United Kingdom
Quinones form an important class of natural products exhibiting a wide range of biological properties (cytotoxic, antifungal, antiviral), together with a great structural diversity and complexity, which makes them interesting challenges to organic synthesis. One of the five main sub-structural groups of quinones are benzoquinones, to which belong 2-methoxy-6-pentadecyl-1,4-benzoquinone 1 and arnebifuranone 2. In addition, a few quinones, like longithorone B 3, possess unique and more complex architectures (Figure 1).

We describe herein the synthesis of different quinones using a microwave-assisted Claisen rearrangement of allyl ethers as one of the key steps.1 This allowed us to complete the short total synthesis of quinones 1 and 2. Since it is also possible to carry out Mitsunobu reactions under microwave conditions,2 we have developed a new microwave-assisted “one-pot Mitsunobu coupling/Claisen rearrangement cascade” for the ortho allylation of phenol derivatives (Scheme 1a). Short reaction times and high yields have been observed within a range of substituted phenols and allylic alcohols. This method has been successfully used in the totally microwave-promoted synthesis of natural products of biological importance, like 1 (Scheme 1b).

Studies are also ongoing towards the synthesis of 3 using a novel “microwave-irradiated double Claisen rearrangement”/ring-closing metathesis sequence.