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

Abstract

To investigate lignin degradation, scientists commonly use model compounds. Unfortunately, these models are most of the time simple β-O-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 G-possessing side-chains and both robust β-5 bond and labile β-O-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 N2 between a phenolate and a bromoketoester, and (3) a modified Upjohn dihydroxylation or a palladium-catalyzed hydrogenation. (β-5)-(β-O-4) dihydroxytrimer and dihydrotrimer of coniferyl alcohol (G) were obtained in good global yield, 9 and 20%, respectively, over nine steps starting from ferulic acid.

A Putative Lignin Copper Oxidase from Trichoderma reesei

“…The reactions were carried out for 24 h at 30 °C with 850 rpm shaking and 3 different lignin dimers were used as substrates: BMA32 (SS βO4), AMA170 (SS syringaresinol) and AMA181 (GG β5). The dimers were synthesized using previously described methods [ 61 ] for dimers BMA32, AMA170 and [ 62 ] for dimer AMA181). The description of the HPSEC and LC-MS analysis and the parameters used have been previously detailed [ 42 ].…”

An Introduction to Model Compounds of Lignin Linking Motifs; Synthesis and Selection Considerations for Reactivity Studies

“…Others have taken the approacho fs ynthesizing as pecific linkingm otif or as eries of linking motifs and then combining them in discrete non-dimerization reactions to generate the desired oligomeric product. Each linking motif is combined with af unctional group or masked functional group, which can be used in subsequent steps to build-up the desired oligomer.T his approach is somewhat more versatile as it does not necessarily result in symmetrical modelc ompounds.T his approach has been used to synthesize trimers [58,[150][151][152][153][154] , and tetramers [151] (3 linking motifs (b-O-4) (b-O-4) (b-O-4)).A n example of this approach reported by Lahive et al [56] is shown in Scheme18i nwhich a( b-O-4) (b-5) model compound of general structure 58 is synthesized.T he approach essentially follows the b-5 Method1aa pproach of dimerizing 21 to generate the b-5 Type C-1 as outlined in Scheme 5. This was followed by methylation or tert-butyldimethylsilyle ther (TBS) phenol protection and an oxidative cleavage step to install an aldehyde group.T his allowed the application of the Nakasubo methodo fb-O-4 synthesis as outlined in Scheme 1b,f ollowed by reduction and, if necessary,T BS removal to give access to the desired (b-O-4) (b-5) model compound.…”

“…This approach is somewhat more versatile as it does not necessarily result in symmetrical model compounds. This approach has been used to synthesize trimers (2 linking motifs (β‐O‐4) (β ‐ 1), (β ‐ 5) (β‐O‐4) and multiple (β‐O‐4) (β‐O‐4)), and tetramers (3 linking motifs (β‐O‐4) (β‐O‐4) (β‐O‐4)). An example of this approach reported by Lahive et al .…”

Combining Laccase-Mediated Dimerization of Resveratrol and Centrifugal Partition Chromatography: Optimization of E-Labruscol Production and Identification of New Resveratrol Dimers

“…25 Resveratrol conversion was monitored to validate the enzymatic activity of laccase as well as the resveratrol availability in solution, the latter being only sparingly soluble in water (0.3 mg•L −1 ). 26 Laccase having already proven to be active in biphasic media, 17,27 a first set of experiments was conducted in ethyl acetate (EtOAc) and highly pure water (Milli-Q grade) or buffer solutions (EtOAc/aqueous phase 3:1 v/v). Considering that laccase activity is high between pH 3 and 7, 25 the influence of pH on resveratrol conversion was monitored by HPLC within this range for 1.5 h (Figure 2).…”