Biocatalytic Transamination of Aldolase‐Derived 3‐Hydroxy Ketones

Although optical pure amino alcohols are in high demand due to their widespread applicability, they still remain challenging to synthesize, since commonly elaborated protection strategies are required. Here, a multi-enzymatic methodology is presented that circumvents this obstacle furnishing enantioenriched 1,3-amino alcohols out of commodity chemicals. A Type I aldolase forged the carbon backbone with an enantioenriched aldol motif, which was subsequently subjected to enzymatic transamination. A panel of 194 TAs was tested on diverse nine aldol products prepared through different nucleophiles and electrophiles. Due to the availability of (R)- and (S)-selective TAs, both diastereomers of the 1,3-amino alcohol motif were accessible. A two-step process enabled the synthesis of the desired amino alcohols with up to three chiral centers with de up to >97 in the final products. (Figure presented.).
This research was funded in part by the Austrian Science Fund (FWF) [J 4242-B21]. M. P. acknowledges funding by the Austrian FWF through an Erwin Schrödinger fellowship and by grants PID2021-122166OB−I00 and PCI2018-092937 funded by MCIN/AEI/10.13039/501100011033, and by “ERDF A way of making Europe” and under the ERACoBioTech (European Union's Horizon 2020 research and innovation programme under grant agreement No [722361]. The authors wish to thank Goran Djordjic for technical assistance and Klaus Zangger for NMR measurements and valuable discussions. The University of Graz and BioHealth Graz are acknowledged for financial support.