Advertisement

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.

ENJOY UNLIMITED ACCES TO C&EN

Synthesis

Chemoenzymatic Path Yields Chiral Amides

Enantioconvergent synthesis converts inexpensive racemic alpha-substituted amides into valuable enantiopure products

by Stephen K. Ritter
October 10, 2011 | A version of this story appeared in Volume 89, Issue 41

By combining an enzymatic reaction step with follow-up chemical synthesis steps, a team led by Dick B. Janssen and Ben L. Feringa of the University of Groningen, in the Netherlands, has developed a simple and efficient method for transforming inexpensive racemic mixtures of chiral compounds into valuable enantiopure products (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201105164). This enantioconvergent synthesis approach, so named because it converts a pair of enantiomers to the single-enantiomer product via different pathways, provides double the yield possible when compared with standard methods that only go after the molecule with the desired stereochemistry in a racemic mixture. The researchers chose to target amides substituted in the α-position by an N, O, or S substituent. α-Substituted amides are important chiral building blocks in medicinal chemistry for the synthesis of antibiotics and peptide-based enzyme inhibitors, among other compounds. The researchers first used a haloalkane dehalogenase enzyme to convert racemic brominated amides into a mixture of bromo- and hydroxyl-substituted amides. In subsequent chemical steps they added the desired N, O, or S nucleophile, such as benzylamine, phenol, or ethanethiol, to convert the intermediates into the enantiopure α-substituted amide.

Article:

This article has been sent to the following recipient:

0 /1 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.