Total Synthesis Blog

Today, very interesting total synthesis of natural products isolated from liverwort Radula perrottetii and Radula variabilis – Radulanin H. Its structure is shown below:

Radulanin H exhibits inhibitory activity aganist cyclooxygenase. It has no stereocentres but contains seven-membered heterocyclic ring with trisubstituted double bond and highly-substituted aromatic ring. Concise synthesis of this aromatic ring is the challange.

So how this synthesis was planned?

It’s not a surprise that ring-closing metathesis was used in contruction of heterocyclic ring. This simplification reveals compound A which can be prepared from phenol B by introduction of two allyl groups in Claisen and Williamson reactions. Now, question arises – in which way aromatic ring B (with all substituents on their places) can be synthesised? Well, for such complex system authors of paper have chosen synthesis from acyclic substrates:

It’s not very obvious how this can be done by using ethyl acetoacetate and benzyl bromide – so let’s see how this synthesis has been acomplished.

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