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Totally Synthetic by Paul H. Docherty, 14 June 2006

Total Synthesis of Galbulimima Alkaloid 13


M. Movassaghi, D. K. Hunt, M. Tjandra, J. Am. Chem. Soc. 2006, 128, 8126-8127.

DOI: 10.1021/ja0626180

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

A simple Diels-Alder reaction (DA) installs the A and B rings with excellent endo:exo selectivity, and leads to the next cyclisation substrate after a few steps.

Radical abstraction of the vinyl bromide led to cyclisation onto the α,β-unsaturated imine, providing the C-ring, and enamine addition to the deprotected carbonyl led to D-ring fomation. Reduction with sodium 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 very 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.