Hot news on an old story

Some stories never seem to end. The hexacyclinol story is one of them. Is it over now?

I assume most readers will be familiar with the controversy about the two proposed structures of hexacyclinol, the original one (1) and a revised one (2), and about a total synthesis of 1 by James LaClair that was challenged by Rychnovsky and Porco on the basis of calculations and a synthesis of 2. The debate has been extensively covered in the blogosphere, e.g. in C&EN and by Derek Lowe.

Proposed structures of hexacyclinol

Proposed structures of hexacyclinol

There is some new evidence now. An Italian group have simulated the 1H and 13C NMR spectra of both structures using DFT calculations (Org. Lett. ASAP). The calculated spectra seem to point to 2 as the correct structure. In addition, 1 cannot have the same spectra as 2 according to the calculations. The authors summarize: “The structure of hexacyclinol is confirmed to be 2. Furthermore, if 1 had been synthesized or was formed from an unforeseen reaction, its NMR spectra are sufficiently different from those of 2 as to guarantee their distinction.” This seems to exclude LaClair’s claim that structure 1, which is the target of his total synthesis, happens to have the same spectral data as 2. The authors of the paper are of course reluctant to draw the obvious conclusion.

Update: This piece of news has been covered in Derek Lowe’s blog. There has been quite a discussion, with James LaClair participating in person! It has also appeared in The Chem Blog.

4 Comments

  1. But is the story over?

  2. Is the Xenobe Institute hiring?

    • You know, if I were the confrontational sort, I’d drive down there and ask him in person. (If I could get my car out of the Wal-Mart with my new tires, that is…)

  3. I published on Computer Assisted Structure Elucidation applied to hexacyclinol last year… http://www.chemconnector.com/chemunicating/the-full-nmr-assignment-of-hexacyclinol-using-case-now-published.html . this paper is also worth reading if you like the hexacyclinol story. What I disagree with from the latest paper is: “DFT calculations are a fast, affordable and reliable means to predict the NMR spectra ….” What’s the definition of fast??? I’ve written previously about FAST NMR predictions and QM is not fast relative to other methods: http://www.chemspider.com/blog/an-invitation-to-collaborate-on-open-notebook-science-for-an-nmr-study.html

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