Chemo-Enzymatic Cascade Synthesis of D-Danshensu and Its Derivatives from Lignin

Abstract

D-Danshensu (D-3,4-dihydroxyphenyllactic acid, D-DSS) and its derivatives exhibit significant pharmacological activities.However, their natural extraction is constrained by low yield and purity, making the development of efficient synthetic routes highly desirable. Lignin, as the most abundant renewable source of aromatic compounds, holds great potential for high-value utilization, which is crucial for enhancing the economic viability of biorefining. Efficient production of D-DSS from lignin is highly desired but extremely challenging. Herein, we report a chemo-enzymatic cascade strategy for synthesizing D-DSS and its derivative methyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (MDHP) starting from lignin, which involves lignin oxidative depolymerization, aldol condensation, followed by α, β-elimination, reduction, and demethylation. Under optimized conditions, this strategy afforded D-DSS and MDHP from pine with mass yields of 17.7 wt% and 20.9 wt% (based on klason lignin), respectively. Techno-economic analysis and life cycle assessment indicate that this innovative strategy is not only economically competitive but also more environmentally friendly and sustainable than traditional plant extraction processes.