A Ketone-Accepting Pictet-Spenglerase for the Asymmetric Construction of 1,1-Disubstituted Tetrahydro-ß-carboline Alkaloids.

ABSTRACT: In light of the ubiquity of 1,1'-disubstituted tetrahydro-ß-carboline (THBC) motif in alkaloid natural products, developing asymmetric methodology for its preparation is highly valuable. Despite the immense progress toward achieving stereoselective Pictet-Spengler reaction with aldehydes, the analogous reaction with ketones is still underdeveloped. Exploiting KslB, a Pictet-Spenglerase from the biosynthesis of kitasetaline, we develop a general, diastereoselective, and protecting-group free method for the construction of densely functionalized THBCs with α-quaternary center by coupling tryptophan derivatives and α-keto acids. We determine the stereochemistry of kitasetalic acid, KslB's physiological product and a key biosynthetic intermediate toward kitasetaline, and established that KslB'

SUBMITTER: Jiang R 

PROVIDER: S-EPMC12516925 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature