2026-10-14T17:44:29Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33969701 2026-09-23T03:06:39Z category_1 category_4 category_12 category_21 category_24 category_873 category_132 category_135 portal_63 item_type_3 month_year_09_2026

Biocatalytic Redox Cascade Enabled Site-Selective Direct β‑Alkylation of Cyclopentanones Rupeng Dai (7817822) Hui Wang (30400) Jincheng Lei (8487909) Yuxuan Ye (1930549) Biophysics Biochemistry Cell Biology Biotechnology Evolutionary Biology Chemical Sciences not elsewhere classified Infectious Diseases Computational Biology widely practiced transformations type radical addition one redox cascade extensive methods exist precise enzyme control driven enzyme repurposing substituted cyclic ketones diverse alkyl groups controlled site selectivity selective direct β cyclic ketones site selectivity enzyme catalyst direct β synergistic tuning specific installation single flavin significant challenge providing trans position adjacent organic synthesis light activation highly site excellent diastereoselectivity disubstituted cyclopentanones catalytic versatility carbonyl compounds also achieved Alkylation of carbonyl compounds is among the most widely practiced transformations in organic synthesis. While extensive methods exist for functionalization at the ipso and α-positions, direct β-alkylation remains a significant challenge, especially for cyclic ketones. Furthermore, catalyst-controlled site selectivity in the β-alkylation of α-aryl- or alkyl-substituted cyclic ketones is rarely achieved using existing methods. Herein, we report a highly site-selective direct β-C(sp³)–H alkylation of α-nonacyl-substituted cyclopentanones via photobiocatalysis. Through mechanism-driven enzyme repurposing, a single flavin-dependent ‘ene’-reductase (ERED) orchestrates two mechanistically distinct transformations, desaturation and Giese-type radical addition, in one redox cascade. Precise enzyme control over site selectivity in the desaturation step ensures site-specific installation of diverse alkyl groups at the β-position adjacent to the α-substituent, providing trans-α,β-disubstituted cyclopentanones with excellent diastereoselectivity. A site-divergent alkylation is also achieved through synergistic tuning of enzyme catalyst and light activation, underscoring the catalytic versatility of EREDs and their potential in streamlining complex molecule synthesis. 2026-09-22T00:00:00Z Dataset Dataset 10.1021/jacs.6c16346.s001 https://figshare.com/articles/dataset/Biocatalytic_Redox_Cascade_Enabled_Site-Selective_Direct_Alkylation_of_Cyclopentanones/33969701 CC BY-NC 4.0