(+)-Strychnine

(–)-Strychnine, the natural form of the notorious toxin, was the Molecule of the Week for December 2, 2013. Robert B. Woodward’s 1954 classical total synthesis of the alkaloid helped him win the Nobel Prize in Chemistry for 1965.

(+)-Strychnine, the molecule’s non-natural enantiomer, presents, if anything, a more difficult synthesis. The feat was first accomplished in 1995 by Larry E. Overman’s research group at the University of California, Irvine. They claimed the first asymmetric total synthesis of (–)-strychnine and used a similar reaction sequence to produce the (+)-enantiomer.

Borrowing on techniques used in more recent syntheses of the (–) isomer, Yong Qin and co-workers at the West China School of Pharmacy (Chengdu) reported a more concise synthesis of (+)-strychnine in late 2018. Qin’s method required 13 reaction steps, including two cascade reactions: a photolytic radical cascade and a bioinspired oxidation–rearrangement.

(+)-Strychnine’s properties appear to have been studied very little, if at all. Of course, its fundamental physical and chemical properties should be the same as those of its enantiomer (see fast facts box). But whether its toxicology is similar to that of its mirror twin remains to be seen.