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Galbulimima Alkaloid 13   

14 June 2006 6,650 views 5 Comments

Galbulimima.jpg

Movassaghi, Hunt and Tjandra. JACS, 2006, ASAP. DOI: 10.1021/ja0626180

Movassaghi et al. at MIT have completed a nice synthesis of Galbulimima alkaloid 13, using some smart cyclisations. Related structures have shown potential as Alzheimer’s disease treatment”s, so this class of structure could be very useful.

Galbulimima_2.jpg

A simple DA [4+2] installs the A and B rings with excellent endo : exo selectivity, and leads to the next cyclisation substrate after a few steps.
Galbulimima_3.jpg

Radical abstraction of the vinyl bromide led to cyclisation onto the alpha,beta-unsaturated imine, providing the C-ring, and enamine additionto the deprotected carbonyl led to D-ring fomation. Reduction with borohydride then took the imine to the amine in a diastereoselective process, creating (-)-A and (+)-B in 70% in total (B is the 2-epi-enantiomer of A) [1]. Although an annoyance to have two diastereoisomer, the authors report that they could be separated with ease using normal chromatographic techniques. This is still unfortunate, as half the material is wasted in some senses, but both diatstereomers are useful, so perhaps it is just an opertunity for more biological testing. Otherwise, this is an laudibly quick synthesis, which may be used for other similar stuctures.

[1] I haven’t described the proposed conformations for these processes as the authors do an excellent job in the paper.

Update:

Here’s a less complex diagram of Galbulimima Alkaloid 13.

Galbulimima_4.jpg

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5 Comments

  • rb says:

    this is a slick synthesis. I have seen Movassaghi give a talk before (when he was interviewing for jobs) and that is one smart dude. Some douche bag tried to give him a hard time about some reaction and Movassaghi went straight to the chalk board started drawing mechanisms… he basically bitch slapped the heckler.

  • ddd says:

    Yea I saw him too on job talk, he went on chalk board to defend himself. Some wittig reaction or so

  • Tot. Syn. says:

    One thing is that the natural product doesn’t need to be drawn in that conformation. It certainly looks intimidating like that, but it can be drawn pretty much flat. I kept the way it was drawn in the paper for consistancy, but I’ll upload a flat(er) stucture later today.

  • ddd says:

    they should be drawn in 3D, but in this case the drawing is weird

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