Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 142, Issue 46, Pages 19754-19762Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.0c09994
Keywords
-
Categories
Funding
- Ministerio de Ciencia e Innovacion (MICIN)
- Fondo Europeo de Desarrollo Regional (FEDER) [RTI2018-094637-B-I00, PGC2018-095808-B-I00]
- Programacion Conjunta Internacional, through the initiative ERA CoBioTech (Tralaminol) [PCI2018-092937]
Ask authors/readers for more resources
The congested nature of quaternary carbons hinders their preparation, most notably when stereocontrol is required. Here we report a biocatalytic method for the creation of quaternary carbon centers with broad substrate scope, leading to different compound classes bearing this structural feature. The key step comprises the aldol addition of 3,3-disubstituted 2-oxoacids to aldehydes catalyzed by metal dependent 3-methyl-2-oxobutanoate hydroxymethyltransferase from E. coli (KPHMT) and variants thereof. The 3,3,3-trisubstituted 2-oxoacids thus produced were converted into 2-oxolactones and 3-hydroxy acids and directly to ulosonic acid derivatives, all bearing gem-dialkyl, gem-cycloalkyl, and spirocyclic quaternary centers. In addition, some of these reactions use a single enantiomer from racemic nucleophiles to afford stereopure quaternary carbons. The notable substrate tolerance and stereocontrol of these enzymes are indicative of their potential for the synthesis of structurally intricate molecules.Y
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available