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

Abstract

Stereopure aliphatic diols are an interesting class of compounds because of their potential applications as precursors for chemical catalysts, for high-value polymers, or as precursors for cyclic acetals. We present a simultaneous enzymatic two-step, one-pot cascade for the synthesis of vicinal diols with excellent de and ee values with the exemplary reaction system from butanal to (4S,5S)-octanediol. This reaction is restricted by an unfavorable reaction equilibrium. For an intensification of the reaction toward higher conversions in equilibrium and increased space time yields (STY), aqueous, microaqueous, and biphasic reaction systems for in situ product removal (ISPR) were experimentally investigated and compared. Process concepts for the purification of (4S,5S)-octanediol from each reaction system were developed and assessed in terms of product-specific energy demand. The two-phase reaction system for in situ product removal is favorable for the enzymatic reactions in terms of yield and STY at different time points. In comparison to the aqueous and microaqueous reaction systems, the specific energy demand for (4S,5S)-octanediol recovery is drastically reduced by approximately a factor of seven when performing ISPR using a biphasic system in comparison to an aqueous reaction system.

Effective Production of Selected Dioxolanes by Sequential Bio‐ and Chemocatalysis Enabled by Adapted Solvent Switching

“…Interestingly, CPME, which can be produced from renewable raw materials, turned out to be a solvent that is not only suitable for the biocatalysts but is also advantageous for the activity of the molecular ruthenium catalyst. This benefit of organic media already holds true for the transformation, but in the downstream processing, the advantages of the micro‐aqueous reaction system (MARS) become even clearer [34] . This system can be used in the future for further combination of chemo‐enzymatic cascades incorporating, for example, CO 2 fixation.…”

Application of Biobased Solvents in Asymmetric Catalysis

“…This same group has published another simultaneous one-pot two-step cascade for the preparation of (4 S ,5 S )-octanediol ( 65 ), as shown in Figure 33 [ 139 ].…”

Three Sides of the Same Coin: Combining Microbial, Enzymatic, and Organometallic Catalysis for Integrated Conversion of Renewable Carbon Sources

“…They can be synthesized by microbes but need less complex reactors during catalysis as compared to whole-cells. They can function, if carefully designed, at high temperatures [5], in unconventional media, like microaqueous reaction systems (MARS) [6], and also in continuous processes, which were pioneered by Prof. Wandrey, to whom this special issue is dedicated [7,8]. Novel tools in enzyme engineering and reaction optimization also allow the use of harsher reaction conditions, enabling the access of product concentrations known from chemical conversions.…”

“…Due to acetaldehyde's high vapor pressure, this compound evaporates from the bioreactor and thus ''distills itself''. Based on this product, Spo ¨ring and Graf von Westarp et al [6] have established a two-step enzymatic cascade for the conversion of these bio-based acetaldehydes to vicinals in a microaqueous (MARS) environment. As the 2,3-butanediol is product in a monophasic organic phase, downstream processing is extremely facilitated [6].…”

“…Based on this product, Spo ¨ring and Graf von Westarp et al [6] have established a two-step enzymatic cascade for the conversion of these bio-based acetaldehydes to vicinals in a microaqueous (MARS) environment. As the 2,3-butanediol is product in a monophasic organic phase, downstream processing is extremely facilitated [6]. Thus, by combining different catalytic strategies, novel production routes can open up, minimizing downstream costs and making green biomanufacturing more attractive.…”