Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Asymmetric Chemoenzymatic Synthesis of (-)-Podophyllotoxin and Related Aryltetralin Lignans.

ABSTRACT: (-)-Podophyllotoxin is one of the most potent microtubule depolymerizing agents and has served as an important lead compound in antineoplastic drug discovery. Reported here is a short chemoenzymatic total synthesis of (-)-podophyllotoxin and related aryltetralin lignans. Vital to this approach is the use of an enzymatic oxidative C-C coupling reaction to construct the tetracyclic core of the natural product in a diastereoselective fashion. This strategy allows gram-scale access to (-)-deoxypodophyllotoxin and is readily adaptable to the preparation of related aryltetralin lignans.

SUBMITTER: Li J

PROVIDER: S-EPMC6688964 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Asymmetric Chemoenzymatic Synthesis of (-)-Podophyllotoxin and Related Aryltetralin Lignans.

Li Jian J Zhang Xiao X Renata Hans H

Angewandte Chemie (International ed. in English) 20190717 34

(-)-Podophyllotoxin is one of the most potent microtubule depolymerizing agents and has served as an important lead compound in antineoplastic drug discovery. Reported here is a short chemoenzymatic total synthesis of (-)-podophyllotoxin and related aryltetralin lignans. Vital to this approach is the use of an enzymatic oxidative C-C coupling reaction to construct the tetracyclic core of the natural product in a diastereoselective fashion. This strategy allows gram-scale access to (-)-deoxypodop ...[more]

PMID: 31241812

Similar Datasets

Enhanced Aryltetralin Lignans Production in Linum Adventi-Tious Root Cultures.

Project description:Lignans are the main secondary metabolites synthetized by Linum species as plant defense molecules. They are also valuable for human health, in particular, for their potent antiviral and antineoplastic properties. In this study, the adventitious root cultures of three Linum species (L. flavum, L. mucronatum and L. dolomiticum) were developed to produce aryltetralin lignans. The effect of two elicitors, methyl jasmonate and coronatine, on aryltetralin lignans production was also evaluated. The adventitious root cultures from L. dolomiticum were obtained and analyzed for the first time and resulted as the best producer for all the aryltetralins highlighted in this system: Podophyllotoxin, 6-methoxypodophyllotoxin and 6-methoxypodophyllotoxin-7-O-β-glucoside, the last showing a productivity of 92.6 mg/g DW. The two elicitors differently affected the production of the 6-methoxypodophyllotoxin and 6-methoxypodophyllotoxin-7-O-β-glucoside.

| S-EPMC8434161 | biostudies-literature

Purity Assessment of Aryltetralin Lactone Lignans by Quantitative 1H Nuclear Magnetic Resonance.

Project description:In the present work, a quantitative 1H Nuclear Magnetic Resonance (qHNMR) was established for purity assessment of six aryltetralin lactone lignans. The validation of the method was carried out, including specificity, selectivity, linearity, accuracy, precision, and robustness. Several experimental parameters were optimized, including relaxation delay (D1), scan numbers (NS), and pulse angle. 1,4-Dinitrobenzene was used as internal standard (IS), and deuterated dimethyl sulfoxide (DMSO-d6) as the NMR solvent. The purities were calculated by the area ratios of H-2,6 from target analytes vs. aromatic protons from IS. Six aryltetralin lactone lignans (deoxypodophyllotoxin, podophyllotoxin, 4-demethylpodophyllotoxin, podophyllotoxin-7'-O-?-d-glucopyranoside, 4-demethylpodophyllotoxin-7'-O-?-d-glucopyranoside, and 6''-acetyl-podophyllotoxin-7'-O-? -d-glucopyranoside) were analyzed. The analytic results of qHNMR were further validated by high performance liquid chromatography (HPLC). Therefore, the qHNMR method was a rapid, accurate, reliable tool for monitoring the purity of aryltetralin lactone lignans.

| S-EPMC6272673 | biostudies-literature

Chemoenzymatic Total Synthesis of Deoxy-, epi-, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones.

Project description:Podophyllotoxin is probably the most prominent representative of lignan natural products. Deoxy-, epi-, and podophyllotoxin, which are all precursors to frequently used chemotherapeutic agents, were prepared by a stereodivergent biotransformation and a biocatalytic kinetic resolution of the corresponding dibenzylbutyrolactones with the same 2-oxoglutarate-dependent dioxygenase. The reaction can be conducted on 2 g scale, and the enzyme allows tailoring of the initial, "natural" structure and thus transforms various non-natural derivatives. Depending on the substitution pattern, the enzyme performs an oxidative C-C bond formation by C-H activation or hydroxylation at the benzylic position prone to ring closure.

| S-EPMC6563474 | biostudies-literature

Chemoenzymatic Asymmetric Synthesis of Complex Heterocycles: Dihydrobenzoxazinones and Dihydroquinoxalinones

Project description:Chiral dihydrobenzoxazinones and dihydroquinoxalinones

| S-EPMC9486952 | biostudies-literature

Antigiardial Activity of Podophyllotoxin-Type Lignans from Bursera fagaroides var. fagaroides.

Project description:Giardiasis, a diarrheal disease, is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; unfortunately, all of them have variable efficacies and adverse effects. Bursera fagaroides has been known for its anti-inflammatory and antidiarrheal properties in Mexican traditional medicine. We investigated the in vitro anti-giardial activities of four podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides, namely, 5'-desmethoxy-β-peltatin-A-methylether (5-DES), acetylpodophyllotoxin (APOD), burseranin (BUR), and podophyllotoxin (POD). All lignans affected the Giardia adhesion and electron microscopy images revealed morphological alterations in the caudal region, ventral disk, membrane, and flagella, to different extents. Only 5-DES, APOD, and POD caused growth inhibition. Using the Caco-2 human cell line as a model of the intestinal epithelium, we demonstrated that APOD displayed direct antigiardial killing activity and low toxicity on Caco-2 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.

| S-EPMC6154107 | biostudies-literature

Asymmetric Chemoenzymatic One-Pot Synthesis of α-Hydroxy Half-Esters.

Project description:A new chemoenzymatic one-pot strategy has been developed for the synthesis of α-hydroxy half-esters containing consecutive quaternary and tertiary stereocenters using asymmetric cascade catalysis. In this study, an asymmetric Ca2+-catalyzed [2,3]-Wittig rearrangement reaction was proven to be suitable for a combination with porcine liver esterase-mediated hydrolysis resulting in the enhanced enantiomeric purity of the obtained products in a one-pot synthesis compared to the stepwise method.

| S-EPMC8359131 | biostudies-literature

Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans.

Project description:Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands.

| S-EPMC5979590 | biostudies-literature

Chemoenzymatic asymmetric synthesis of pregabalin precursors via asymmetric bioreduction of β-cyanoacrylate esters using ene-reductases.

Project description:The asymmetric bioreduction of a library of β-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications.

| S-EPMC3579311 | biostudies-literature

Substrate specificity of FUT8 and chemoenzymatic synthesis of core-fucosylated asymmetric N-glycans.

Project description:Substrate specificity studies of human FUT8 using 77 structurally-defined N-glycans as acceptors showed a strict requirement towards the ?1,3-mannose branch, but a great promiscuity towards the ?1,6-mannose branch. Accordingly, a chemoenzymatic strategy was developed for the efficient synthesis of core-fucosylated asymmetric N-glycans.

| S-EPMC4852481 | biostudies-literature

Chemoenzymatic Dynamic Kinetic Asymmetric Transformations of β-Hydroxyketones.

Project description:Herein we report on the development and application of chemoenzymatic Dynamic Kinetic Asymmetric Transformation (DYKAT) of α-substituted β-hydroxyketones (β-HKs), using Candida antartica lipase B (CALB) as transesterification catalyst and a ruthenium complex as epimerization catalyst. An operationally simple protocol allows for an efficient preparation of highly enantiomerically enriched α-substituted β-oxoacetates. The products were obtained in yields up to 95 % with good diastereomeric ratios.

| S-EPMC9293354 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data