Happy Couple

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Science  18 Feb 2011:
Vol. 331, Issue 6019, pp. 823-825
DOI: 10.1126/science.331.6019.823-d

In principle, dimeric molecules may seem easier to synthesize than lower-symmetry compounds of comparable size. After all, both halves can be generated together and then conveniently coupled at the end. In practice, the coupling step often poses a tremendous challenge—all the more frustrating because it comes after long and meticulous preparation of the penultimate monomer. Such was the case with the polycyclic core of lomaiviticin, an organic natural product of exploratory pharmaceutical interest. The compound comprises two identical tetracyclic frameworks linked by a C-C bond and two C-O bonds; an especially unusual feature is the presence in each half of a diazo group, ordinarily a highly reactive substituent. Herzon et al. have now succeeded in assembling the lomaiviticin framework (without the pendant sugars in the natural product) using 11 steps, perhaps the hardest of which proved to be the formation of that central C-C bond. After an extensive search, the authors discovered that a trivalent manganese complex bearing three fluorinated acetylacetonate ligands was a uniquely selective oxidant for the coupling reaction (though the bacterial solution to the same challenge remains somewhat mysterious).

J. Am. Chem. Soc. 133, 10.1021/ja200034b (2011).

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