A major challenge in chemical synthesis is to develop catalytic systems that convert simple molecules to complex high-value products. Often these valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Of great interest are enantioenriched amine diastereomers, which are prevalent in pharmaceuticals and agrochemicals, 1 yet their preparation often relies on low-e ciency multi-step synthesis. 2 Herein, we report the discovery and characterisation of a multi-functional biocatalyst, which operates using a previously unreported conjugate reduction-reductive amination mechanism. This enzyme (pIR-120), identi ed within a metagenomic imine reductase (IRED) collection 3 and originating from an unclassi ed Pseudomonas species, possesses an unusual active site architecture that facilitates an amine-activated conjugate alkene reduction followed by reductive amination. This enzyme enables the coupling of a broad selection of α,β-unsaturated carbonyls with amines for the e cient preparation of enantioenriched amine diastereomers. Moreover, employing a racemic substrate partner or conjugated dienyl-ketone provides a means of controlling additional stereocentres using the single catalyst. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by pIR-120 which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.

The synthetic biology toolbox lacks extendable and conformationally controllable yet easy-to-synthesize building blocks that are long enough to span membranes. To meet this need, an iterative synthesis of α-aminoisobutyric acid (Aib) oligomers was used to create a library of homologous rigid-rod 310-helical foldamers, which have incrementally increasing lengths and functionalizable N- and C-termini. This library was used to probe the inter-relationship of foldamer length, self-association strength, and ionophoric ability, which is poorly understood. Although foldamer self-association in nonpolar chloroform increased with length, with a ∼14-fold increase in dimerization constant from Aib6 to Aib11, ionophoric activity in bilayers showed a stronger length dependence, with the observed rate constant for Aib11 ∼70-fold greater than that of Aib6. The strongest ionophoric activity was observed for foldamers with >10 Aib residues, which have end-to-end distances greater than the hydrophobic width of the bilayers used (∼2.8 nm); X-ray crystallography showed that Aib11 is 2.93 nm long. These studies suggest that being long enough to span the membrane is more important for good ionophoric activity than strong self-association in the bilayer. Planar bilayer conductance measurements showed that Aib11 and Aib13, but not Aib7, could form pores. This pore-forming behavior is strong evidence that Aibm (m ≥ 10) building blocks can span bilayers.

Consumer's needs and desires for green, natural and sustainable cosmetic ingredients has driven the advances in technology needed to synthesise these ingredients using biocatalytic methods, which are described in this review.

Copper catalyzed multi-functionalization of unsaturated carbon-carbon bonds is a powerful tool for the generation of complex molecules. We report a regiodivergent process that allows a switch between 1,4-borocupration and 4,1-borocupration of 1,3-dienes upon a simple change in ligand. The subsequently generated allyl coppers are trapped in an electrophilic cyanation to selectively generate densely functionalized and synthetically versatile 1,2- or 4,3-borocyanation products.

A highly enantio‐ and diastereoselective copper‐catalyzed three‐component coupling affords the first general synthesis of homoallylic amines bearing adjacent stereocenters from achiral starting materials. The method utilizes a commercially available NHC ligand and copper source, operates at ambient temperature, couples readily available simple imines, allenes, and diboranes, and yields high‐value homoallylic amines that exhibit versatile amino, alkenyl, and boryl units.