posted on 2024-01-19, 12:36authored byAleksandra Rudzka, Natalia Antos, Tamara Reiter, Wolfgang Kroutil, Paweł Borowiecki
Chiral alcohols are
versatile building blocks and are of particular
interest in the asymmetric synthesis of nonracemic active pharmaceutical
ingredients, agrochemicals, fragrances, flavors, natural products,
etc. Herein, we report on a “one-pot sequential two-step”
concurrent oxidation–reduction photobiocatalytic process to
synthesize enantiomerically enriched alcohols. In this regard, an
efficient photocatalytic system based on irradiation with 440 nm blue
LEDs in the presence of 9-fluorenone as a metal-free photocatalyst
and molecular oxygen as the terminal oxidant in dry DMSO as the hydrogen
peroxide-neutralizing agent was used to oxidize a broad range of racemic
(hetero)benzylic alcohols into prochiral ketones quantitively (>99%
conv.). The in situ formed carbonyl compounds were subsequently converted
into the corresponding chiral alcohols via a sequential biocatalytic
transhydrogenation catalyzed by lyophilized E. coli cells overexpressing highly stereoselective and stereocomplementary
recombinant alcohol dehydrogenases (ADHs) originated from Rhodococcus ruber (E. coli/ADH-A) or Rhodococcus erythropolis (E. coli/ReADH)
to obtain (S)-alcohols and Lactobacillus
kefir (E. coli/Lk-ADH) or KRED-110 to obtain
(R)-alcohols, respectively. Overall, the elaborated
photobiocatalytic deracemization of racemic alcohols using a 9-fluorenone-O2-blue LED-DMSO-E. coli/ADH system carried
out on a semipreparative scale (0.25 mmol; 63 mM final conc. in 4
mL) at room temperature yielded nonracemic aryl alcohols with 82–99.9%
conv., in up to 92% isolated yield, with 97–99.9% ee and complementary
chirality.