If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.



Chemists Devise Kilogram-Scale Route To Chiral Lactone Building Block

Four-step synthesis and chiral resolution of Taniguchi lactone requires no chromatography

by Carmen Drahl
May 12, 2014 | A version of this story appeared in Volume 92, Issue 19

Don’t be fooled by the Taniguchi lactone’s small structure—it’s been a starting point in some big syntheses, including the first stereoselective assembly of quinine. Chemists have a handful of ways of making the lactone. But those routes didn’t work at the kilogram scale required by Fredrik von Kieseritzky of Swedish organic electronics firm Arubedo; Yeliu Wang of contract research organization Beijing Honghui Meditech, in China; and Magnus Axelson of Sweden’s Karolinska University. So the trio took matters into their own hands. Their four-step synthesis and chiral resolution method is capable of producing kilogram quantities of a single enantiomer of the Taniguchi lactone without any chromatography, which saves time, solvent, and money (Org. Process Res. Dev. 2014, DOI: 10.1021/op500096j). After assembling the racemic lactone, the team developed a process to obtain the single enantiomer. They first opened the ring with (S)-1-benzylmethylamine and a titanium dehydrating agent. Those conditions hadn’t been used before, but they successfully obtained a mixture of ring-opened products. Then they isolated the needed intermediate by crystallization. Finally, they chose acidic hydrolysis to re-form the (S)-Taniguchi lactone. Chemists typically conduct that step under basic conditions, which aren’t amenable to kilogram scales, the researchers note. They add that the titanium-mediated step is likely to work for other lactones.


This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.