Enantioselective Syntheses of Lignin Models: An Efficient Synthesis of β‐O‐4 Dimers and Trimers by Using the Evans Chiral Auxiliary

Abstract

We describe an efficient five-step, enantioselective synthesis of (R,R)- and (S,S)-lignin dimer models possessing a β-O-4 linkage, by using the Evans chiral aldol reaction as a key step. Mitsunobu inversion of the (R,R)- or (S,S)-isomers generates the corresponding (R,S)- and (S,R)-diastereomers. We further extend this approach to the enantioselective synthesis of a lignin trimer model. These lignin models are synthesized with excellent ee (>99 %) and high overall yields. The lignin dimer models can be scaled up to provide multigram quantities that are not attainable by using previous methodologies. These lignin models will be useful in degradation studies probing the selectivity of enzymatic, microbial, and chemical processes that deconstruct lignin.

Enantioselective Synthesis of Dilignol Model Compounds and Their Stereodiscrimination Study with a Dye-Decolorizing Peroxidase

“…33 However, our screen on auxiliaries found that 4c had a slightly better diastereoselectivity than 4e ( see Figure S2 and Table S2 in SI). Thus, 4c was selected as the chiral auxiliary for subsequent preparations.…”

“…Thus, the stereospecific anti -dilignols were obtained in just four steps with an overall 42% yield, which was a significant improvement over the other asymmetric methods reported so far. 32, 33 …”

Evaluation of anticancer potential of Thai medicinal herb extracts against cholangiocarcinoma cell lines

“…Later, cinnamic acid is transformed into three types of lignols including p -coumaryl, coniferyl and sinapyl alcohol, which are the precursors for lignin [48] Acetylation of coniferyl alcohol produces coniferyl acetate, which is converted into eugenol, which in turn has been reported to have an anti-cancer effect through increased apoptosis [49, 50]. In this study, the proposed lignin structure consists of two coniferyl acetate linking with an ether bond, namely a β-O-4 linkage [51]. A previous study has shown that lignin fractions obtained from the conventional fractionation of Acacia nilotica extract had a half inhibitory concentration (IC50) on human breast cancer cell line (MCF-7) lower than 100 μg/mL [52] This is in accordance with our findings with an IC50 on CCA cell lines lower than 63 μg/mL.…”

Oxidative Coupling of â‐O‐4′ Dilignol Models Leading to Polycyclic Products with Rare Interlignol Linkages

“…Thus, model compounds are often employed to simplify product identification and reaction condition optimization. For example, dimeric models that consist of either two simple phenols, or one phenol and one lignol via C−C or C−O linkages (Scheme , i and ii), have been extensively applied to study oxidation, reduction and modification of lignin . Despite their widespread use, those dimers remain compromised in terms of structural feature comparing to those found in authentic lignin largely due to the lack of proper C3 side chain units.…”