Total Synthesis Blog

Deja vu? Maybe yes because (+)-Dodoneine is also – similary to hyptolide – α,β-unsaturated δ-lactone. Just look at the structure of (+)-Dodoneine:

It’s not so complicated (it has only two chiral carbon atoms, hyptolide – four) as hyptolide, but synthetic approach to this target is quite different than to previous one.

But now, let’s say something about its biological properties.

(+)-Dodoneine was isolated from methanolic extract from plant called ‘african mistletoe’ with very nice-sounded latin name Tapinathus dodoneifolius. This plants grow somwhere in West Africa. Authors of paper wrote that ‘african mistletoe’ is applied in treatment of wide spectrum of diseases, including cardiovascular and respiratory. It’s also used as remedy aganist cholera, diarrhoea, stomach ache and wounds. It’s possible that (+)-dodoneine could find interesting medical applications.

In my opinion, (+)-Dodoneine can be synthesized analogically like hyptolide. Proposition of retrosynthesis is shown below:

Authors have chosen other synthetic route:

As you can see – only two olefinations and only two stereoselective aldol condesations. Full retrosynthetic analysis is shown below:
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Today, total synthesis of hyptolide which was published in Tetrahedron Letters. Structure of target molecule is drawn below (click on images to enlarge them ):

Authors wrote about some “important biological activities” and “interesting pharmacological properties” and they wrote nothing more So, what do we have here? Well, four stereocentres, two double bonds and α,β-unsaturated δ-lactone ring makes hyptolide really nice target molecule.

Hyptolide is present in plants from family called Lamiaceae, especially in genera Hyptis and Syncolostemon. There are several compounds related to hyptolide: spicigerolide, anamarine and synrotolide. Their are shown below.

I’ve tried to plan the synthesis of hyptolide and my proposition of retrosynthesis is presented at next images.

I hope that everything is clear (P means some protecting groups)

The real retrosynthesis of hyptolide:
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