A biocompatible alkene hydrogenation merges organic synthesis with microbial metabolism

Abstract

Organic chemists and metabolic engineers use orthogonal technologies to construct essential small molecules such as pharmaceuticals and commodity chemicals. While chemists have leveraged the unique capabilities of biological catalysts for small-molecule production, metabolic engineers have not likewise integrated reactions from organic synthesis with the metabolism of living organisms. Reported herein is a method for alkene hydrogenation which utilizes a palladium catalyst and hydrogen gas generated directly by a living microorganism. This biocompatible transformation, which requires both catalyst and microbe, and can be used on a preparative scale, represents a new strategy for chemical synthesis that combines organic chemistry and metabolic engineering.

Keywords: biotransformations; hydrogenation; metabolism; palladium; synthetic methods.

Figure 1

Biocompatible chemistry enables the integration of non-enzymatic reactions with microbial metabolism. a) Biocompatible chemistry represents a distinct approach for synthesis that employs chemical tools in a biological environment. b) Design of a biocompatible alkene hydrogenation that uses hydrogen gas produced directly by microbial metabolism for synthesis.

Figure 2

Functional group tolerance of the biocompatible hydrogenation. Values shown are isolated yields for preparative scale reactions (5 mM substrate concentration with 8 mol% Royer catalyst in 90 mL of growth medium under an atmosphere of nitrogen in serum bottles shaken at 190 rpm) unless indicated otherwise.^x Isolated yield for a preparative scale reaction run with 16 mol% Royer catalyst.^y The reaction was run with 2.5 mM substrate.

Figure 3

Requirements of the biocompatible hydrogenation and its effect on E.oli. a) Control experiments and metabolite analyses. Reactions were run with 5 mM of substrate 1a and 8 mol% Royer catalyst in 7 mL of growth medium under an atmosphere of nitrogen in 16 mL Hungate tubes shaken at 190 rpm. Conversions were determined by ¹H NMR and are the mean of three replicate experiments. Hydrogen and formic acid were quantified after 18 h using GC. b) Survival of E. coli DD-2 after 18 h reactions measured by serial dilution and plate count. Data shown are the mean of three independent experiments.