Total Synthesis Highlights

amination with the free amine, while at the same time ionic cyclization closed the ether ring.
N-Acylation completed the conversion to 10.
The ether 10 had previously been converted to codeine, and then, in a single demethylation step,
to morphine. In that synthesis, the alkene of 10 was directly epoxidized. The resulting “up”
epoxide reacted only sluggishly with phenylselenide anion, and the relative configuration of the
resulting allylic alcohol had to be inverted by oxidation followed by reduction. In the current
synthesis, exposure of the alkene 10 to dibromohydantoin under aqueous conditions, to form the
bromohydrin, effected concomitant arene bromination, to give, after base treatment, the “down”
epoxide 12. Phenylselenide opening of the epoxide was then facile, and the product allylic alcohol
had the correct relative configuration for codeine and morphine. The extra Br was of no
consequence, as it was removed by the final LiAlH 4 reduction.
Except for the stereogenic center of the acetal, the dienone 1 is prochiral. This raises the exciting
possibility that it may be possible to set the absolute configuration of codeine and thus of
morphine by asymmetric catalysis of the Henry reaction of 1.
D. F. Taber, Org. Chem. Highlights 2010, June 7.
URL: http://www.organic-chemistry.org/Highlights/2010/07June.shtm
12. The Dixon Synthesis of (-)-Nakadomarin A
(-)-Nakadomarin A (4), isolated from the sponge Amphimedon sp. off the coast of Okinama,
shows interesting antifungal and antibacterial activity. The key step in the total synthesis of 4
reported (J. Am. Chem. Soc. 2009, 131, 16632. ) by Darren J. Dixon of the University of Oxford
was the diastereoselective addition of the enantiomerically-pure ester 1 to the prochiral nitroalkene
2.