First Total Synthesis of (β-5)-(β--4) Dihydroxytrimer and Dihydrotrimer of Coniferyl Alcohol (G): Advanced Lignin Model Compounds.

To investigate lignin degradation, scientists commonly use model compounds. Unfortunately, these models are most of the time simple β--4 dimers and do not sufficiently mimic the wide complexity of lignin structure (i.e., aliphatic side chains and robust C-C bonds). Herein, we present a methodology to access advanced lignin models through the first synthesis of two trimers of monolignol -possessing side-chains and both robust β-5 bond and labile β--4 bond-via a chemo-enzymatic pathway. Key steps were (1) the C-C coupling via laccase-mediated oxidation, (2) the C-O coupling via a simple S between a phenolate and a bromoketoester, and (3) a modified Upjohn dihydroxylation or a palladium-catalyzed hydrogenation. (β-5)-(β--4) dihydroxytrimer and dihydrotrimer of coniferyl alcohol () were obtained in good global yield, 9 and 20%, respectively, over nine steps starting from ferulic acid.