From Decades to Minutes: Steps Toward the Structure of Strychnine 1910–1948 and the Application of Today's Technology. Issue 27 (20th April 2020)

• Record Type: Journal Article
• Authors: Seeman, Jeffrey I.; Tantillo, Dean J.
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 27(2020)
• Page Start: 10702
• Page End: 10721
• Publication Date: 2020-04-20
• Subjects: applied computational chemistry––NMR -- R. B. Woodward -- Robert Robinson -- structure determination -- strychnine; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201916566
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Between 1910 and 1947, Robert Robinson (primarily), among others, published numerous proposed structures for strychnine. Robinson published 17 of his strychnine papers with his doctoral advisor William Henry Perkin, Jr., though all but two appeared after Robinson had taken his first permanent academic position. This Essay analyzes 20 key publications leading up to Robinson's (correct, then incorrect, then correct again though not definitively) proposal and Woodward's assignment of the actual structure of strychnine. We subjected the assignment of the strychnine structure to a modern computational quantum chemistry workflow. By computing, with density functional theory, 1 H and 13 C NMR chemical shifts for the literature‐proposed strychnine structures, we were able to rule out most incorrect structures. 13 C NMR predictions were better at this, but 1 H NMR chemical shifts were helpful. A comparison is made between the consequences of publishing erroneous ideas in the first half of the 20th century and doing so in the 21st century. Abstract : Strychnine was the last and greatest of natural products whose structure was determined using the classical methods. This 40‐year story is told by following the trail of 20 key publications, mostly by Robert Robinson, leading up to his tentative, and ultimately R. B. Woodward's, conclusive assignment. Modern quantum mechanical computations are used to select the actual strychnine structure from Robinson's many working hypotheses.