Expanding the scope of asymmetric transformations catalyzed by promiscuous biocatalysts in non-aqueous media Grant uri icon

abstract

  • Transition-metal based catalysts have revolutionized the world of synthetic chemistry, enabling exquisite control of stereochemistry, promoting the formation of previously intractable chemical bonds, and bringing challenging molecular scaffolds firmly within the grasp of synthetic chemists. However, catalyst expense and toxicity are drawbacks to their widespread use. Biocatalytic methods have steadily made inroads into new synthetic territory, offering options that traditional catalysts do not, including environmental friendliness, non-toxicity, and rapid production using standard molecular biology methods. While biocatalysis in non-aqueous media remains a frontier for synthetic chemists, there are two highly encouraging aspects of select classes of biocatalysts: catalytic promiscuity, the ability to catalyze reactions beyond their standard in vivo chemistries, and interfacial activation, the enhanced catalytic activity sometimes observed in less polar surroundings. Lipases have both of these qualities, making them both highly adaptable to the catalysis of classic carbon-carbon bond forming reactions and highly active in organic media. The proposal lays out efforts to investigate the catalytic promiscuity of classic lipase (Porcine Pancreatic Lipase (PPL)) for three class carbon-carbon bond forming reactions: the Robinson annulation, the Morita-Baylis-Hillman reaction, and the Knoevenagel condensation, and details multi-factorial optimization and rational design procedures that focus on optimizing both yields and stereoselectivities. A particular emphasis is placed upon investigation of the lid region of PPL for its impact on reactivity, by replacing the native lid sequence with designed ?-hairpin peptides to investigate the role of rigidity and hydrophobic surface area.

date/time interval

  • September 2020 - August 2021