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Totally Synthetic by Paul H. Docherty, 29 January 2007

Total Synthesis of Phalarine


C. Li, C. Chan, A. C. Heimann, S. J. Danishefsky, Angew. Chem. Int. Ed. 2007, 46, 1448-1450.

DOI: 10.1002/anie.200604072

In a pair of papers in Angewandte, Danishefsky has completed some rather interesting work on the mechanisms of formation and the total synthesis of the structurally interesting alkaloid, Phalarine. This little nugget was isolated from blue canary grass, but there’s precious little data on it’s biological profile, so lets just look at making it for the sake of chemistry!

After a little mundane heterocycle synthesis, things heat up, literally… after cleaving the MOM group, cyclisation / rearrangement leaves them with the core of the natural product. However, appending the the pyrrole ring is a bit more of a challenge, and took two attempts to attain a decent yield. Their sucessful approach relied on a Gassman oxindole synthesis, which starts with the ortho amination of the methoxy benzene, and then functionalistion of the amine:

Just a really neat synthesis of that fragement. BTW, the unsuccessful approach is also worth reading, if only because it involves a Japp-Klingemann condensation with a ketoester. As I mentioned, they also published another paper on the means of biosynthesis and related mechanisms and considerations, which can be found here.