Total Synthesis Blog

Today, some interesting tricyclic target, Alboatrin:

Alboatrin has characteristic cis tetrahydofurane-benzenopyrane system. Also, there is ketal moiety present in this molecule what (in my opinion) can be taken advantage in planning of synthesis of Alboatrin (well, in my retrosynthesis I’ve taken advantage of this fact ).

Let’s say something about properties of our target. Well, Alboatrin was isolated from Verticillium alboatrum (some fungi specie, I guess). It exhibits phytotoxic activity, for example – it inhibits the root growth.

Retrosynthesis is shown below:

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There are four key reactions used in this total synthesis: Claisen rearrangement, intramolecular ketene-alkene cycloaddition, oxidative ring enlargement and stereoselective alkilation in exo position. Synthesis is shown below:

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Synthesis starts with oricnol, 2, which can be obtained from many species of lichens. 2 is converted to 3 under Williamson’s ethers synthesis conditions. Then, 3 in high temperature undergo [3,3]-sigmatropic Claisen rearrangement to give mixture of 4a and 4b in 2:1 ratio. Desired regioisomer 4a was isolated by column chromatography. Next, 4a was converted to 5 in a Williamson-like reaction. Then 5 underwent reaction with p-TsCl and triethylamine and keten moiety was generated in situ. Next, ketene-alkene cycloaddition occured and cyclobutanone 7 was formed. Next, oxidative enlargement of ring was performed to give 8. Then, in few steps (one of them involve stereoselective alkilation of lactone in exo position) Alboatrin 1 was accomplished.

My proposition of retrosynthesis of Alboatrin is presented below. As I wrote above, I tried to take advatage of presence of ketal moiety in target molecule. So, I’ve proposed some tandem-like cyclisation. Oricnol is the starting material in my synthesis, too. I’m waiting for your opinions

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For more pieces of information see:

B. Biswas et al., Tetrahedron, 2008, 64, 3212.