How hard can that be?

July 27, 2026

Researchers achieve first total synthesis of the nominal and actual natural product Benthol A

Illustration of the chemical structure of Benthol A with colored markings and a note indicating a site that was originally misidentified.

Chemical “complexity” has certainly more than one dimension, but almost all chemists likely agree that Benthol A, a compound isolated from a marine dinoflagellate, is not an entirely trivial target. The 72-carbon backbone is decorated with no less than 35 stereogenic centers and four stereogenic olefins; thus, 239 = 549.755.813.888 stereoisomers are possible. Which of these corresponds to the natural product, given that the isolation team apparently made a mistake in the original structural assignment? G. Huang, C. Wirtz, A. Tomio, T. Varlet (not on the photo as he has left the Institute), and A. Fürstner now provide an unambiguous answer to this tricky question—only the secondary alcohol at C40 was misassigned!

In a laboratory, four people are holding a large, complex molecular model that depicts chemical structures and bonds. — The isolation team led by Prof. Dr. Alois Fürstner (right): Dr. Guanghao Huang, Connie Wirtz, and Andrea Tomio. Also involved but not pictured, as he is no longer at the institute, is Dr. Thomas Varlet.

© MPI / Fuerstner

The isolation team led by Prof. Dr. Alois Fürstner (right): Dr. Guanghao Huang, Connie Wirtz, and Andrea Tomio. Also involved but not pictured, as he is no longer at the institute, is Dr. Thomas Varlet.

© MPI / Fuerstner

The entire investigative work required to answer this question and the subsequent first total synthesis of both the nominal and the actual natural product can be found in:

https://pubs.acs.org/doi/10.1021/jacs.6c05580
https://pubs.acs.org/doi/10.1021/jacs.6c05583

By the way: studies on structure-activity relationships of this anti-malaria compound are ongoing.