Synthesis of naturally occurring quinones

ORGN 194

Aouregan M. Jacob, A.M.Jacob@exeter.ac.uk 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.