Single-Electon-Transfer-Mediated Asymmetric Synthesis of Boron-Functionalised Amino Acids and Peptides Empowered by Synergistic Photocatalysis
Lead Research Organisation:
University of Bristol
Department Name: Chemistry
Abstract
Single-electron transfer-mediated transformation enabled by photoredox catalysis has opened up a promising avenue in organic
synthesis. Merging photoredox catalysis with catalytic asymmetric catalysis represents a new and largely unexplored field which
possesses significant potential for the synthesis of those essentially challenging-to-synthesise but valuable enantiopure complex
molecules. Nonproteinogenic enantioenriched amino acids have played a central role in the design of pharmaceutical peptides and
proteins with enhanced biological properties. Furthermore, they act as significant precursors for chiral auxiliaries and chiral catalysts,
and are key building blocks for the construction of biomolecules. Traditional strategies to access enantiopure unnatural amino acids,
such as Strecker reactions, hydrogenation of dehydroamino acids, Mannich-type reactions, and alkylation of iminoesters etc, lie on
the disconnection of polar bonds associated with two-electron transfer chemistry, and often suffer from harsh reaction conditions
and lengthy synthetic sequences, or lack of substrate generality.
Chiral boronic acids and related derivatives are highly valuable building blocks in modern synthesis as they can be easily transformed
stereospecifically into diversely functional groups. Over the last decade, the host group have developed a broad research programme
involving boron chemistry, reporting novel methods for the synthesis of complex molecules and natural products. By taking
advantage of the host's expertise in boron chemistry, in this proposal, we seek to introduce a new methodology by merging
asymmetric photoredox reactions and stereospecific 1,2-metallate rearrangements for the facile synthesis of enantiomerically
enriched boron-functionalised unnatural amino acid derivatives using a synergistic photocatalysis/chiral phosphoric acid catalysis
system.
synthesis. Merging photoredox catalysis with catalytic asymmetric catalysis represents a new and largely unexplored field which
possesses significant potential for the synthesis of those essentially challenging-to-synthesise but valuable enantiopure complex
molecules. Nonproteinogenic enantioenriched amino acids have played a central role in the design of pharmaceutical peptides and
proteins with enhanced biological properties. Furthermore, they act as significant precursors for chiral auxiliaries and chiral catalysts,
and are key building blocks for the construction of biomolecules. Traditional strategies to access enantiopure unnatural amino acids,
such as Strecker reactions, hydrogenation of dehydroamino acids, Mannich-type reactions, and alkylation of iminoesters etc, lie on
the disconnection of polar bonds associated with two-electron transfer chemistry, and often suffer from harsh reaction conditions
and lengthy synthetic sequences, or lack of substrate generality.
Chiral boronic acids and related derivatives are highly valuable building blocks in modern synthesis as they can be easily transformed
stereospecifically into diversely functional groups. Over the last decade, the host group have developed a broad research programme
involving boron chemistry, reporting novel methods for the synthesis of complex molecules and natural products. By taking
advantage of the host's expertise in boron chemistry, in this proposal, we seek to introduce a new methodology by merging
asymmetric photoredox reactions and stereospecific 1,2-metallate rearrangements for the facile synthesis of enantiomerically
enriched boron-functionalised unnatural amino acid derivatives using a synergistic photocatalysis/chiral phosphoric acid catalysis
system.