Access to Lactone Building Blocks via Horse Liver Alcohol Dehydrogenase-Catalyzed Oxidative Lactonization

Abstract

The oxidative lactonization of 1,4-, 1,5-, and 1,6-diols using horse liver alcohol dehydrogenase (HLADH) is reported. Molecular oxygen was used as terminal electron acceptor by utilization of the laccase-mediator concept to regenerate the oxidized nicotinamide cofactor and producing water as sole byproduct. Spontaneous hydrolysis of the lactone products was identified as a major limiting factor toward preparative application of the system, which can be alleviated by using a two liquid phase approach to extracting the product into an organic solvent.

Synthesis of Enantiomerically Enriched 2‐Hydroxymethylalkanoic Acids by Oxidative Desymmetrisation of Achiral 1,3‐Diols Mediated by Acetobacter aceti

“…For 1,5‐diols, only the conversion of the 3‐methyl‐substituted derivative into the corresponding enantiomerically enriched δ‐lactone was investigated, either by using Gluconobacter roseus or by a two‐step oxidation mediated by horse liver alcohol dehydrogenase …”

Recent advances in whole cell biocatalysis techniques bridging from investigative to industrial scale

“…Because of this shift and the supply of two reduction equivalents per molecule of cosubstrate, 90 mol% of cosubstrate are saved in comparison to traditional alcohol cosubstrates, which usually require at least a five-fold molar excess. At the same time, many of the lactones produced in these approaches find potential applications as polymer building blocks and hence represent valuable co-products [18].…”

An Alcohol Dehydrogenase from the Short‐Chain Dehydrogenase/Reductase Family of Enzymes for the Lactonization of Hexane‐1,6‐diol

“…Initial screening reactions gave low yields (less than 10 % conversions) of 1,6‐HD to CL, even with HLADH (Figure S2). Similar to reports by other research groups, neither the hydroxy‐aldehyde nor its cyclic hemiacetal were detected . In an effort to improve the reactions, the CFEs were supplemented with additional cofactor [1 m m NAD(P) + ] and the concentration of the starting material increased to 20 m m .…”

“…The practical application of this class of enzymes are however generally limited due to their requirement for reduced cofactors (NADPH) and thus requirement of co‐substrates for cofactor regeneration, instability and substrate or product inhibition. An alternative to BVMO catalyzed oxygenation of ketones, is the oxidative lactonization of diols utilizing alcohol dehydrogenases (ADHs; Scheme ) or the laccase/TEMPO system …”

“…With advances in cofactor regeneration strategies, the use of purified ADHs has again emerged as a feasible reaction as it alleviates unwanted side product formation. Hollmann and co‐workers demonstrated the use of a laccase‐mediator system for cofactor regeneration of ADH‐mediated lactonization of various diols, where only molecular oxygen is required and water is produced as the sole by‐product as well as photocatalytic regeneration of NAD + . More recently, a novel convergent cascade was developed, combining both BVMO and ADH strategies with no requirement for external cofactor regeneration enzymes .…”