Integrated heterogeneous catalysis and biocatalysis for sustainable synthesis

The development of sustainable methods with applications in synthetic organic chemistry has been investigated widely in recent years. Catalytic processes often provide sustainable strategies with high efficiency, high selectivity and low environmental impact in terms of energy consumption and waste production. In this project, heterogeneous catalysis and biocatalysis have been investigated separately and combined into a two-step process. Gold nanoparticle catalysts supported on inert bulk materials have been applied in the oxidation of alcohol feedstocks as an alternative to stoichiometric oxidation techniques. Synthesis of a range of gold nanoparticle catalysts has been undertaken with variation in support materials and preparation methods. These catalysts have been tested in the oxidation of the benchmark substrate benzyl alcohol, and the substrate scope also extended to include secondary alcohols. The low gold loading and reusability of these heterogeneous catalysts coupled with the use of water as the solvent has provided a sustainable oxidation method for primary and secondary alcohols. Transaminases are enzymes which catalyse the transfer of an amino group to the carbonyl group of an aldehyde or ketone. Screening of transaminases from the UCL transaminase library was undertaken to identify enzymes for application in this project. These enzymes have been applied in the synthesis of furfurylamines from furfurals, in a one-step biocatalytic reaction under mild conditions on a preparative scale. The transaminases were also applied in the synthesis of chiral amines from ketone precursors, with high yields and stereoselectivities achieved. Heterogeneous catalysis and biocatalysis have been coupled together into a novel two-step cascade to produce chiral amines from secondary alcohol feedstocks. The oxidation of secondary alcohols using gold nanoparticle catalysts was followed by the transamination of the ketone intermediates. This process was conducted in one pot, with water as the solvent and no isolation or purification of the ketone intermediate

Selective hydroboration - oxidation of terminal alkenes under flow conditions

Abstract An efficient flow process for the selective hydroboration and oxidation of different alkenes using 9‐BBN allows facile conversion in high productivity (1.4 g/h) of amorpha‐4,11‐diene to the corresponding alcohol, which is an advanced intermediate in the synthesis of the antimalarial drug artemisinin. The in situ reaction of borane and 1,5‐cyclooctadiene using a simple flow generator proved to be a cost efficient solution for the generation of 9‐BBN

Modular chemoenzymatic synthesis of terpenes and their analogues

Non‐natural terpenoids offer potential as pharmaceuticals and agrochemicals. However, their chemical syntheses are often long, complex, and not easily amenable to large‐scale production. Herein, we report a modular chemoenzymatic approach to synthesize terpene analogues from diphosphorylated precursors produced in quantitative yields. Through the addition of prenyl transferases, farnesyl diphosphates, (2E,6E)‐FDP and (2Z,6Z)‐FDP, were isolated in greater than 80 % yields. The synthesis of 14,15‐dimethyl‐FDP, 12‐methyl‐FDP, 12‐hydroxy‐FDP, homo‐FDP, and 15‐methyl‐FDP was also achieved. These modified diphosphates were used with terpene synthases to produce the unnatural sesquiterpenoid semiochemicals (S)‐14,15‐dimethylgermacrene D and (S)‐12‐methylgermacrene D as well as dihydroartemisinic aldehyde. This approach is applicable to the synthesis of many non‐natural terpenoids, offering a scalable route free from repeated chain extensions and capricious chemical phosphorylation reactions