7452-03-1Relevant 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.
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.
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.
