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Phalarine   

29 January 2007 7,596 views 3 Comments

phalarine.jpg

Danishefsky, Li, Chan and Heimann. ACIEE, 2006, EarlyView. 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 chemistry’s sake!

phalarine_1.jpg

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:

phalarine_2.jpg

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.

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3 Comments

  • TWYI says:

    Seriously impressive stuff…

  • Retro says:

    I totally agree. The fact that elucidation of a mechanistically dominant intermediate in the rearrangement of azaspiroindolenine to a precursor of phalarine was successful is quite impressive stuff!

  • TWYI says:

    Reading that paper reminds me that the Gassman indole synthesis is superb IF you can get the SMe off afterwards. I had a nightmare period a couple of years ago trying various conditions on quite an advanced intermediate before settling for a 40% yield for the SMe removal..

    Still they had no trouble, Raney Nickel worked a treat for them!!