Authors
Ruiying Jiang, Nour Wasfy, Takahiro Mori, Megan Hoang, Ikuro Abe, Hans Renata
Published in
Angewandte Chemie (International ed. in English). Pages e202502367. Apr 10, 2025. Epub Apr 10, 2025.
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 towards 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 towards kitasetaline, and established that KslB's selectivity is opposite to what is achieved chemically. Our investigations of KslB show its high activity (total turnover number >438,000), substrate promiscuity, and tolerance for high substrate concentrations (0.1M). Additionally, a TrpB-KslB cascade enables the construction of complex tricyclic products from simple indoles in one-pot. X-ray structural characterization of KslB sheds light on potential active site interactions to account for its stereoselectivity and ability to accept ketone substrates.
PMID:
40209176
Bibliographic data and abstract were imported from PubMed on 11 Apr 2025.
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