The hexacyclinol controversy has taken a very interesting new twist, which I learned about on Friday from Dylan Stiles. To recap: the molecule is a complex natural product, which was the subject of a total synthesis paper earlier this year by James La Clair. The paper had several unusual features, such as single authorship with acknowledgements to several unnamed co-workers, an odd source (the "Xenobe Research Institute" and "Bionic Bros. GmbH" and (not least) several key chemical steps that appear to make little sense, backed up by fishy NMR data.
Then Prof. Scott Rychnovsky of UC-Irvine popped up with a proposal that the structure of hexacyclinol had been wrongly assigned in the first place. He assigned a completely different structure, with rather solid-looking reasoning behind it, which raised the question of just what La Clair had synthesized. How can you get the right spectral data by making the wrong structure, when the structures are so different as to make that impossible?
Turns out that Rychnovsky had another ace to turn over. The web site for Angewandte Chemie, where the original La Clair paper ran, has now put up advance notice of a paper on the synthesis of the revised structure of hexacyclinol, which appears to indeed match the published spectral data. This grenade is from
Paul John Porco at BU, some of his students, and. . .Scott Rychnovsky, who apparently wasn't going out on as much of a limb as I thought.
La Clair has seen the writing on the wall, and apparently realizes that he has indeed been weighed in the balance and found wanting. During the day on Friday, the Xenobe Research Institute web page was updated. It now features Rychnovsky's revised structure (Update: or does it? See the comments!), with this text:
Desoxoudol (previously named desoxohexacyclinol)...
Efforts are underway to identify pathways that regulate the growth and development of four parasites responsible for Malaria, Plasmodium vivax, P. malariae, P. falciparum and P. ovale. Our first study conducted on desoxohexacyclinol, currently renamed as desoxoudol, is a terpene isolated from cultures of a German Borstiger Knäueling mushroom (Lentinus strigosus = Panus rudis Fr.). Earlier 2006, Dr. La Clair published the synthesis of desoxoudol demonstrated its conversion to udol and 5-epi-udol. Due to the unconventional nature of this effort, efforts are now underway to repeat this isolation and synthesis. Samples of these intermediates will be verified through analysis by a panel of external laboratories.
Unconventional. . .well, yeah, in a way. It's unconventional to synthesize a complex molecule and get the NMR structure of something completely different, that's for sure. But it's very conventional indeed to go back and attempt to spray-paint the record to make it appear as if something strange and embarassing hadn't happened. Oh, that part happens all the time. And that's exactly what I think is going on here.
For more comments on all this, see the Stiles link and The Chemblog. This is turning into the biggest stink-bomb in organic synthesis in many years.