Biocatalytic Asymmetric Synthesis Of Heterocyclic Alpha,Alpha-Disubstituted Amino Acids

Researchers at the University of California, Santa Barbara have bridged a gap in the biocatalysis field by devising an efficient technique for synthesizing heterocyclic α,α-disubstituted α-amino acids. This two-step artificial biocatalytic route uses recombinant Lo1T to catalyze Mannich cyclization on a variety of imine substrates which are spontaneously formed in situ. This Lo1T-based biocatalytic technique affords access to a variety of pyrrolidine and piperidine-based α,α-disubstituted α-AAs from simple, commercially available aldehyde and diamino acid substrates. Moreover, Lo1T demonstrated excellent diastereomeric and enantiomeric excess towards a broad range of imine substrates. Beyond noncanonical amino acids, this technique can also make strained heterocycles, such as pyrrolizidine, indolizidine, and quinolizidine, which are important pharmacophores for making new therapeutics. This novel approach of using a PLP-dependent enzyme to catalyze intramolecular Mannich reactions in order to make heterocyclic alpha-quaternary amino acids provides the basis for future protein engineering work that will improve catalytic efficiency and stereoselectivity towards further substrates.

Website

https://techtransfer.universityofcalifornia.edu/NCD/32888.html?utm_source=AUTMGTP&utm_medium=webpage&utm_term=ncdid_32888&utm_campaign=TechWebsites

Advantages

  • Enables synthesis of heterocyclic α,α-disubstituted α-amino acids
  • Excellent stereoselectivity (diastereomeric excess >95) towards a broad range of imine substrates
  • Able to synthesize strained heterocycles, such as pyrrolizidine, indolizidine, and quinolizidine

Potential Applications

  • Biocatalysis
    • Therapeutics

Contact Information

Name: Mary Raven

Email: raven@tia.ucsb.edu