Totally Synthetic by Paul H. Docherty, 24 April 2006
Total Synthesis of Abyssomicin C
K. C. Nicolaou, S. T. Harrison, Angew. Chem. Int. Ed. 2006, 45, 3256-3260.
An interesting approach to the abyssomicin family, this time of the C variant. Without getting into the DMDO-related debacle of the Sorensen and Snider papers (though the discrepancy is worth a read!), this is an incredibly popular target. Unsurprising, I guess, due to it’s biological profile, but I’m sure we’ll see a few more syntheses before the year is out.
Nicolaou’s route uses an impressive Diels-Alder reaction to put in the six-member ring, generating two stereocenters, in a process somewhat similar to Ward’s. The reaction goes in an impressive 80% yield, leaving a single diastereoisomer. The five member-ring is then created using a Dieckmann cyclisation, and regioselective epoxide opening. Nice end-game too, using RCM, and some interesting conclusions!