Premium
Biocatalyzed C−C Bond Formation for the Production of Alkaloids
Author(s) -
Patil Mahesh D.,
Grogan Gideon,
Yun Hyungdon
Publication year - 2018
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201801130
Subject(s) - chemistry , enantioselective synthesis , enzyme , alkaloid , chemical synthesis , biocatalysis , substrate (aquarium) , organic synthesis , combinatorial chemistry , stereochemistry , organic chemistry , catalysis , biochemistry , reaction mechanism , biology , ecology , in vitro
Traditional methods of chemical synthesis of alkaloids exhibit various problems such as lack of enantioselectivity, the use of toxic chemical and intermediates, and multiple numbers of synthetic steps. Consequently, various enzymatic methods for the formation of C−C bonds in the alkaloid skeleton have been developed. Herein, we report advances achieved in the enzymatic or chemo‐enzymatic synthesis of pharmaceutically important alkaloids that employ three C−C bond forming enzymes: two Pictet‐Spenglerases and the oxidative C−C bond forming flavoenzyme Berberine Bridge Enzyme. Protein engineering studies, improving the substrate scope of these enzymes, and thereby leading to the synthesis of non‐natural alkaloids possessing higher or newer pharmacological activities, are also discussed. Furthermore, the integration of these biocatalysts with other enzymes, in multi‐enzymatic cascades for the enantioselective synthesis of alkaloids, is also reviewed. Current results suggest that these enzymes hold great promise for the generation of C−C bonds in the selective synthesis of alkaloid compounds possessing diverse pharmacological properties.