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.
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.
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.
