Hexacyclinol

Natural products chemist Udo Gräfe collected a sample of P. rudis HKI 0254 from a dead log in Siberia from which hexacyclinol was isolated. His group's 2002 paper showed that the compound behaved as an antiproliferative drug against cancer cell lines and proposed a structure (2) for the compound.^[1]

An initial total synthesis was published by James J. La Clair in 2006, purporting a synthesis of Gräfe's proposed structure based on ¹H nuclear magnetic resonance (NMR) spectra.^[2] Natural products chemist Scott D. Rychnovsky simulated the ¹³C nuclear magnetic resonance spectrum of the structure proposed by Gräfe and found that it did not correspond to the spectrum of the structure allegedly synthesized by La Clair. Rychnovsky proposed a different structure (1) based on panepophenanthrin, another molecule isolated from a different strain of P. rudis.^[3] The scientific community then began criticizing La Clair's work, claiming that his work was sloppy or that he fabricated data.^[4] La Clair's publication of his purported synthesis was retracted in 2012, citing a lack of validation of its claims.^[5]

In 2006, a group led by John Porco, Jr. synthesized Rychnovsky's proposed structure. They showed that the ¹H- and ¹³C-NMR spectra matched that of the compound isolated by Gräfe, confirming Rychnovsky's structure.^[6] La Clair claimed that since the two structures were isomers, it is possible that they would have similar ¹H-NMR spectra.^[4] However, a later paper by Saielli and Bagno claims that there would be significant differences in the ¹H- and ¹³C-NMR spectra of compounds (1) and (2).^[7]

The controversy was covered extensively by a number of science blogs.^[8]

In response to the controversy, Nobel Prize-winning synthetic chemist E.J. Corey remarked, "Occasionally, blatantly wrong science is published, and to the credit of synthetic chemistry, the corrections usually come quickly and cleanly."^[4]