Cell-Free CO₂ Valorization to C6 Pharmaceutical Precursors via a Novel Electro-Enzymatic Process

The healthcare industry emits significant amounts of CO2 and has an imperative need for decarbonization. This study demonstrated a new hybrid electro-enzymatic process that converts waste CO2 into high-value C6 pharmaceutical precursor compounds. A novel three-chamber electrolyzer equipped with a Cu-based gas diffusion electrode converted gaseous CO2 into ethanol at a high current density (40–60 mA/cm2), high selectivity (43–81 mol %), and production rate (368–428 mg/L/h). Purified ethanol from the electrolyzer was then sent to an enzymatic bioreactor where ADH and DERA enzymes upgraded ethanol into C6 statin precursor molecules at high yields (29–35%) via acetaldehyde. Competitive C6 lactol synthesis rates (4.7–5.7 mM/day) and titers (712–752 mg/L) were achieved, demonstrating the potential of the end-to-end process. The C6 lactol product can seamlessly be converted to statins, a class of lipid-lowering medication that is among the largest selling class of drugs in the world. This hybrid process provides a new pathway for CO2 valorization to high-value products and accelerates healthcare sector decarbonization

Asymmetric <i>C</i>‑Alkylation of Nitroalkanes <i>via</i> Enzymatic Photoredox Catalysis

Tertiary nitroalkanes and the corresponding α-tertiary amines represent important motifs in bioactive molecules and natural products. The C-alkylation of secondary nitroalkanes with electrophiles is a straightforward strategy for constructing tertiary nitroalkanes; however, controlling the stereoselectivity of this type of reaction remains challenging. Here, we report a highly chemo- and stereoselective C-alkylation of nitroalkanes with alkyl halides catalyzed by an engineered flavin-dependent “ene”-reductase (ERED). Directed evolution of the old yellow enzyme from Geobacillus kaustophilus provided a triple mutant, GkOYE-G7, capable of synthesizing tertiary nitroalkanes in high yield and enantioselectivity. Mechanistic studies indicate that the excitation of an enzyme-templated charge-transfer complex formed between the substrates and cofactor is responsible for radical initiation. Moreover, a single-enzyme two-mechanism cascade reaction was developed to prepare tertiary nitroalkanes from simple nitroalkenes, highlighting the potential to use one enzyme for two mechanistically distinct reactions

Synthesis and Biological Evaluation of Sophoridinol Derivatives as a Novel Family of Potential Anticancer Agents

New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 μM. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration–time curve (AUC) of 10.3 μM·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells