Post Tagged with: "Hexacyclinol"

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.

By February 13, 2009 4 comments synthetic chemistry