551-29-1Relevant articles and documents
Dirigent Proteins Guide Asymmetric Heterocoupling for the Synthesis of Complex Natural Product Analogues
Kim, Stacie S.,Sattely, Elizabeth S.
supporting information, p. 5011 - 5021 (2021/05/04)
Phenylpropanoids are a class of abundant building blocks found in plants and derived from phenylalanine and tyrosine. Phenylpropanoid polymerization leads to the second most abundant biopolymer lignin while stereo- and site-selective coupling generates an array of lignan natural products with potent biological activity, including the topoisomerase inhibitor and chemotherapeutic etoposide. A key step in etoposide biosynthesis involves a plant dirigent protein that promotes selective dimerization of coniferyl alcohol, a common phenylpropanoid, to form (+)-pinoresinol, a critical C2 symmetric pathway intermediate. Despite the power of this coupling reaction for the elegant and rapid assembly of the etoposide scaffold, dirigent proteins have not been utilized to generate other complex lignan natural products. Here, we demonstrate that dirigent proteins from Podophyllum hexandrum in combination with a laccase guide the heterocoupling of natural and synthetic coniferyl alcohol analogues for the enantioselective synthesis of pinoresinol analogues. This route for complexity generation is remarkably direct and efficient: three new bonds and four stereocenters are produced from two different achiral monomers in a single step. We anticipate our results will enable biocatalytic routes to difficult-to-access non-natural lignan analogues and etoposide derivatives. Furthermore, these dirigent protein and laccase-promoted reactions of coniferyl alcohol analogues represent new regio- and enantioselective oxidative heterocouplings for which no other chemical methods have been reported.
Profiling of the formation of lignin-derived monomers and dimers from: Eucalyptus alkali lignin
Hu, Zhenhua,Li, Suxiang,Lu, Fachuang,Shi, Lanlan,Wang, Chen,Yue, Fengxia,Zhang, Han,Zhao, Chengke
supporting information, p. 7366 - 7375 (2020/11/18)
Lignin is a renewable and the most abundant aromatic source that can be used for extensive chemicals and materials. Although approximately 50 million tons of lignin are produced annually as a by-product of the pulp and paper industry, it is currently underutilized. It is important to know the structural features of technical lignin when considering its application. In this work, we have demonstrated the formation of low-molecular-weight constituents from hardwood (Eucalyptus) lignin, which produces much more low-molecular-weight constituents than softwood (spruce) lignin, after a chemical pulping process, and analyzed the micromolecular compositions in the alkali lignin after fractionation by dichloromethane (DCM) extraction. By applying analytical methods (gel-permeation chromatography, 2D NMR and GC-MS) with the aid of evidence from authenticated compounds, a great treasure trove of lignin-derived phenolic compounds from Eucalyptus alkali lignin were disclosed. Except for some common monomeric products, as many as 15 new lignin-derived monomers and dimers including syringaglycerol, diarylmethane, 1,2-diarylethanes, 1,2-diarylethenes, (arylvinyl ether)-linked arylglycerol dimers and isomeric syringaresinols were identified in the DCM-soluble fraction. Regarding the formation and evolution of the Cα-condensed β-aryl ether structure, a novel route that is potentially responsible for the high content of β-1 diarylethenes and diarylethanes in the lignin low-molecular-weight fraction, in addition to the β-1 (spirodienone) pathway, was proposed. This work not only provides novel insights into the chemical transformation of S-G lignin during the alkali pulping process, but also discovered lignin-derived phenolic monomers and dimers that can potentially be used as raw materials in the chemical or pharmaceutical industries. This journal is
Syringaresinol inhibits UVA-induced MMP-1 expression by suppression of mapk/ap-1 signaling in hacat keratinocytes and human dermal fibroblasts
Joo, Yung Hyup,Karadeniz, Fatih,Ko, Jaeyoung,Kong, Chang-Suk,Oh, Jung Hwan
, (2020/06/08)
Ultraviolet (UV) irradiation induces detrimental changes in human skin which result in photoaging. UV-induced intracellular changes cause degradation of extracellular matrix (ECM). UV-stimulated cleavage of collagen in ECM occurs via matrix metalloproteinases (MMPs). (±)syringaresinol (SYR), a phytochemical which belongs to the lignan group of polyphenols, was investigated for its ability to reverse the UVA-induced changes in human HaCaT keratinocytes and dermal fibroblasts (HDFs) in vitro. Effect of SYR on UVA-induced changes was investigated by production and activation of MMPs and its transcriptional upstream effectors; mitogen-activated protein kinases (MAPKs) and pro-inflammatory mediators. Levels of expression were determined using ELISA, RT-PCR and immunoblotting. UVA irradiation stimulated the production of MMP-1 and inhibited collagen production. SYR treatment suppressed MMP-1 and enhanced collagen production in UVA-irradiated HaCaT keratinocytes and HDFs. SYR repressed the UV-induced phosphorylation of p38, ERK and JNK MAPKs in HaCaT keratinocytes while only suppressing JNK phosphorylation in HDFs. In addition, SYR was able to inhibit UVA-induced production of inflammatory cytokines; TNF-α, COX-2, IL-1β and IL-6. Moreover, SYR suppressed the activator protein-1 (AP-1), a heterodimer of phosphorylated transcription factors c-Jun and c-Fos. SYRtreatment decreased nuclear levels of activated c-Fos and c-Jun as a mechanism to inhibit UVAinduced transcriptional activities leading to MMP-1 production. In conclusion, current results demonstrated that SYR could inhibit UVA-induced upregulation of MMP-1 by suppressing MAPK/AP-1 signaling in HaCaT keratinocytes and HDFs. Therefore, SYR was suggested as a potential compound with antiphotoaging properties against UVA-induced skin aging.
