Alkaloid Puzzle Resolved | Chemical & Engineering News
Volume 92 Issue 20 | p. 30 | Concentrates
Issue Date: May 19, 2014

Alkaloid Puzzle Resolved

Department: Science & Technology
News Channels: Organic SCENE
Keywords: organic synthesis, total synthesis, biosynthesis, computational chemistry

Chemists have yet to learn all of the molecule-making tactics of the family of fungi that produces penicillin. And as a research report shows, collaborative efforts to further unravel fungal biosynthetic pathways can help scientists find new antibacterial and antitumor agents (Nature 2014, DOI: 10.1038/nature13273). Richmond Sarpong and his group at the University of California, Berkeley, had run into a fungal alkaloid structure elucidation problem that left them scratching their heads and issuing a call for help. They expected the alkaloids citrinalin B and cyclopiamine B to be pseudoenantiomers—that is, nearly mirror images of one another. Yet that’s not what the reported structures for the molecules indicated. The Berkeley team proposed a new structure for citrinalin B and asked UC Davis computational chemist Dean J. Tantillo for backup. The calculations supported the idea that the original structure of citrinalin B had been misassigned. Armed with that evidence, Sarpong’s lab collaborated with Yale University’s Scott J. Miller to carry out chemical syntheses that confirmed the revised structure. With Roberto G. S. Berlinck of the University of São Paulo, in Brazil, Sarpong’s team pursued additional biosynthesis studies. Those results support a long-held idea that citrinalin, cyclopiamine, and related molecules come from a precursor containing a bicyclo[2.2.2]diazaoctane. What’s more, they discovered a new molecule, citrinalin C, which they think may be such a precursor.

By correcting the structure of citrinalin B (revised stereocenters in red) so that it is a pseudoenantiomer of cyclopiamine B, chemists found supporting evidence for a common precursor for two bioactive compounds.
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