Naturalproductman’s Blog

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Total Synthesis of Nakadomarin

Posted by naturalproductman on November 2, 2009

Darren Dixon and co-workers at the University of Oxford published in JACS on the total synthesis communication of nakadomarin. This manzamine alkaloid is a beautiful molecule with a hexacyclic carbon skeleton – 8,5,5,5,15,6 ring system. The final step was of course the ring closing metathesis; however unlike the previously reported syntheses, this one formed the Z-olefin of the 15-membered ring in favor over the E-olefin. The trick was to use R- or S- CSA to protonate the amine; but they don’t really explain the reason why adding a Bronstead acid favors the Z-olefin in the RCM reaction.

The second to the last step involved the pentacyclic ring formation that involves the coupling between a five membered lactam and a furan via reduction with one equivalent of DIBAL followed by heating in HCl to dehydrate and form an iminium ion that gets trapped by the furan via a Friedel-Crafts like cyclization.

nakadomarin


JACS paper

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