24404-50-0Relevant 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.
Sesquiterpenoids, phenolic and lignan glycosides from the roots and rhizomes of Clematis hexapetala Pall. and their bioactivities
Cai, Lu,Han, Shao-Wei,Li, Shuai,Shao, Si-Yuan
, (2020/10/12)
Approximately 17 compounds were isolated from a 60% EtOH aqueous extract of the roots and rhizomes of Clematis hexapetala Pall., including three new guaianolide sesquiterpenoids with 5/7/5-fused rings and 3S-configuration (1–3), five new prenylated tetra-substituted phenolic glycosides (4–8) with 6/6-fused 9H-benzopyran skeleton (5) and 6/7-fused 7,10-dihydro-benzoxepin skeleton (6–8), one new isoferulyl glucoside (9), two new furofuran lignan diglucosides (10–11), and six known compounds. The chemical structures of the new compounds were elucidated via spectroscopic data and electronic circular dichroism (ECD) analyses in combination with a modified Mosher's method. The possible biosynthetic relationships of prenylated tetra-substituted phenols were postulated. In the in vitro assays, compound 16 exhibited moderate TNF-α secretion inhibitory activity with IC50 value of 3.419 μM. Compounds 14–16 displayed potent PTP1B enzymatic inhibitory activities with inhibition ratios of 48.30–86.00%. And compound 16 showed significant PTP1B enzymatic inhibition with IC50 value of 4.623 μM.
Pinoresinol-lariciresinol reductase: Substrate versatility, enantiospecificity, and kinetic properties
Davin, Laurence B.,Hwang, Julianne K.,Lewis, Norman G.,Moinuddin, Syed G. A.
, (2020/03/26)
Two western red cedar pinoresinol-lariciresinol reductase (PLR) homologues were studied to determine their enantioselective, substrate versatility, and kinetic properties. PLRs are downstream of dirigent protein engendered, coniferyl alcohol derived, stereoselective coupling to afford entry into the 8- and 8′-linked furofuran lignan, pinoresinol. Our investigations showed that each PLR homolog can enantiospecifically metabolize different furofuran lignans with modified aromatic ring substituents, but where phenolic groups at both C4/C4′ are essential for catalysis. These results are consistent with quinone methide intermediate formation in the PLR active site. Site-directed mutagenesis and kinetic measurements provided additional insight into factors affecting enantioselectivity and kinetic properties. From these data, PLRs can be envisaged to allow for the biotechnological potential of generation of various lignan skeleta, that could be differentially “decorated” on their aromatic ring substituents, via the action of upstream dirigent proteins.
Isolation of enantiomeric furolactones and furofurans from Rubus idaeus L. with neuroprotective activities
Zhou, Le,Han, Feng-Ying,Lu, Li-Wei,Yao, Guo-Dong,Zhang, Ying-Ying,Wang, Xiao-Bo,Lin, Bin,Huang, Xiao-Xiao,Song, Shao-Jiang
, p. 122 - 129 (2019/05/29)
A phytochemical study on the fruits of Rubus idaeus L. (Rosaceae) yielded eight pairs of enantiomeric lignans, including one undescribed furolactone named (?)-idaeusinol A and six undescribed furofuran derivatives named (+/?)-idaeusinol B–D. The structures of these isolated compounds were elucidated by spectroscopic analyses and a combination of computational techniques including gauge-independent atomic orbital (GIAO) calculation of 1D NMR data and TD-DFT calculation of electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that (+)-idaeusinol D exhibited the most significant protective effect against H2O2-induced neurotoxicity at the concentration of 25 μM. In contrast, (?)-idaeusinol D, as the enantiomer of (+)-idaeusinol D, showed no effect against H2O2-induced neurotoxicity at both 25 and 50 μM concentration.
An Efficient Method for Determining the Relative Configuration of Furofuran Lignans by 1H NMR Spectroscopy
Shao, Si-Yuan,Yang, Ya-Nan,Feng, Zi-Ming,Jiang, Jian-Shuang,Zhang, Pei-Cheng
supporting information, p. 1023 - 1028 (2018/05/01)
An efficient 1H NMR spectroscopic approach for determining the relative configurations of lignans with a 7,9′:7′,9-diepoxy moiety has been established. Using the chemical shift differences of H2-9 and H2-9′ (ΔδH-9 and ΔδH-9′), the configurations of 8-H and 8-OH furofuran lignans can be rapidly and conveniently determined. The rule is applicable for data acquired in DMSO-d6, methanol-d4, or CDCl3. Notably, the rule should be applied carefully when the C-2 or C-6 substituent of the aromatic rings may alter the dominant conformers of the furofuran moiety.
Non-host disease resistance response in pea (Pisum sativum) pods: Biochemical function of DRR206 and phytoalexin pathway localization
Seneviratne, Herana Kamal,Dalisay, Doralyn S.,Kim, Kye-Won,Moinuddin, Syed G.A.,Yang, Hong,Hartshorn, Christopher M.,Davin, Laurence B.,Lewis, Norman G.
, p. 140 - 148 (2015/05/27)
Continually exposed to potential pathogens, vascular plants have evolved intricate defense mechanisms to recognize encroaching threats and defend themselves. They do so by inducing a set of defense responses that can help defeat and/or limit effects of invading pathogens, of which the non-host disease resistance response is the most common. In this regard, pea (Pisum sativum) pod tissue, when exposed to Fusarium solani f. sp. phaseoli spores, undergoes an inducible transcriptional activation of pathogenesis-related genes, and also produces (+)-pisatin, its major phytoalexin. One of the inducible pathogenesis-related genes is Disease Resistance Response-206 (DRR206), whose role in vivo was unknown. DRR206 is, however, related to the dirigent protein (DP) family. In this study, its biochemical function was investigated in planta, with the metabolite associated with its gene induction being pinoresinol monoglucoside. Interestingly, both pinoresinol monoglucoside and (+)-pisatin were co-localized in pea pod endocarp epidermal cells, as demonstrated using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging. In addition, endocarp epidermal cells are also the site for both chalcone synthase and DRR206 gene expression. Taken together, these data indicate that both (+)-pisatin and pinoresinol monoglucoside function in the overall phytoalexin responses.
The synthesis and analysis of advanced lignin model polymers
Lancefield,Westwood
supporting information, p. 4980 - 4990 (2015/11/16)
If the lignin-first biorefinery concept becomes a reality, high quality lignins close in structure to native lignins will become available in large quantities. One potential way to utilise this renewable material is through depolymerisation to aromatic chemicals. This will require the development of new chemical methods. Here, we report the synthesis and characterisation of advanced lignin model polymers to be used as tools to develop these methods. The controlled incorporation of the major linkages in lignin is demonstrated to give complex hardwood and softwood lignin model polymers. These polymers have been characterised by 2D HSQC NMR and GPC analysis and have been compared to isolated lignins.
A bio-inspired total synthesis of tetrahydrofuran lignans
Albertson, Anna K. F.,Lumb, Jean-Philip
supporting information, p. 2204 - 2208 (2015/02/19)
Lignan natural products comprise a broad spectrum of biologically active secondary metabolites. Their structural diversity belies a common biosynthesis, which involves regioand chemoselective oxidative coupling of propenyl phenols. Attempts to replicate this oxidative coupling have revealed significant challenges for controlling selectivity, and these challenges have thus far prevented the development of a unified biomimetic route to compounds of the lignan family. A practical solution is presented that hinges on oxidative ring opening of a diarylcyclobutane to intercept a putative biosynthetic intermediate. The effectiveness of this approach is demonstrated by the first total synthesis of tanegool in 4 steps starting from ferulic acid, as well as a concise synthesis of the prototypical furanolignan pinoresinol.
New lignans from the aerial parts of Rudbeckia laciniata
Lee, Seung Young,Woo, Kyeong Wan,Kim, Chung Sub,Lee, Dong Ung,Lee, Kang Ro
, p. 320 - 325 (2013/03/28)
Three new furofuran lignans, (+)-4,4′-O-diangeloylpinoresinol (1), (+)-4,4′-O-diangeloylmedioresinol (2), and (+)-4,4′-O- diangeloylsyringaresinol (3), together with the known compound (+)-syringaresinol, were isolated from the MeOH extract of Rudbeckia l
Four new cytotoxic tetrahydrofuranoid lignans from sinopodophyllum emodi
Sun, Yan-Jun,Li, Zhan-Lin,Chen, Hong,Liu, Xiao-Qiu,Zhou, Wei,Hua, Hui-Ming
body text, p. 480 - 484 (2012/06/30)
Four new tetrahydrofuranoid lignans, (-)-tanegool-7′-methyl ether (1), (+)-7′-methoxylariciresinol (2), sinolignan C (3), and epipinoresinol-4,4-di-Oβ- D-glucopyranoside (4), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with one known lignan (5). Their structures and stereochemistry were elucidated on the basis of spectroscopic and mass spectrometric evidence. The isolation of compounds 1-5 represents the first report of tetrahydrofuran lignans from the genus Sinopodophyllum. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines, and compound 1 showed the most potent cytotoxicity with ICvalues of 9.7 μM and 4.7 μM, respectively.
