One‐Pot Enzymatic Synthesis of Cyclic Vicinal Diols from Aliphatic Dialdehydes via Intramolecular C−C Bond Formation and Carbonyl Reduction Using Pyruvate Decarboxylases and Alcohol Dehydrogenases

Abstract

An enzymatic cascade reaction was developed for one-pot enantioselective conversion of aliphatic dialdehydes to chiral vicinal diols using pyruvate decarboxylases (PDCs) and alcohol dehydrogenases (ADHs). The PDCs showed promiscuity in catalysing the cyclization of aliphatic dialdehydes through intramolecular stereoselective carbon-carbon bond formation. Consequently, 1,2-cyclopentanediols in three different stereoisomeric forms and 1,2-cyclohexanediols in two different stereoisomeric forms could be prepared with high conversion and stereoisomeric ratio from the respective initial substrates, glutaraldehyde and adipaldehyde. These cascade reactions represent a promising approach to the biocatalytic synthesis of important chiral vicinal diols.

Preparation of a whole cell catalyst overexpressing acetohydroxyacid synthase of Thermotoga maritima and its application in the syntheses of α-hydroxyketones

“…It is a very important function of E. coli AHAS to catalyze the enantiospecific condensation of pyruvate and BA to form R -PAC 10 . We therefore checked whether TmcAHAS also possesses this activity.…”

“…But the low catalytic efficiency of the mutant largely prevents its practical application. Recent studies have shown that PDCs have some advantages in the formation of intramolecular C–C bonds from substituted benzaldehydes or aliphatic dialdehydes 9 , 10 .

Figure 1 Enantiospecific condensation reactions catalyzed by AHAS.

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Practical Enzymatic Production of Carbocycles

“…Clapés and coworkers [46] first found that the TPP‐dependent benzaldehyde lyase BAL exhibits some degree of catalytic promiscuity and is able to catalyze intramolecular benzoin condensation of ether‐tethered substrates. Based on this discovery, Zhu and coworkers [47] developed TPP‐dependent pyruvate decarboxylases (PDCs) for the synthesis of α‐hydroxy‐cyclopentanone 4.2 and α‐hydroxy‐cyclohexanone 4.5 with moderate to high conversion and ee (Scheme 14). Moreover, this transformation could be coupled with ketone reduction with alcohol dehydrogenase (ADH) in a biocatalytic cascade process to generate chiral vicinal diols 4.3 and 4.6 .…”

Enzymatic Cascade in a Simultaneous, One-Pot Approach with In Situ Product Separation for the Asymmetric Production of (4S,5S)-Octanediol

“…Some bulk diols, such as 2,3-butanediol, can be produced from glucose by members from the Klebsiella family. , For the production of stereopure vicinal, aliphatic diols, there are routes either via chemical synthesis, such as Sharpless asymmetric dihydroxylation starting from dienes, or enzymatic routes, starting from diketones via a double reduction using alcohol dehydrogenases . Other enzymatic routes to vicinal, diols are shown in the work of Zhang et al or Qiu et al for the production of a statin precursor . Although nonaliphatic diols are targeted, a similar approach was used as in this work.…”