4263-88-1Relevant 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.
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.
