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Special Issue "Molecular Transformations of Natural Products"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 April 2018)

Special Issue Editors

Guest Editor
Prof. Dr. Vladimír Křen

Institute of Microbiology, Academy of Sciences of the Czech Republic, Laboratory of Biotransformation, National Centre of Biocatalysis and Biotransformation, Videnska 1083, CZ 142 20 Praha 4, Czech Republic
Website | E-Mail
Fax: +420 296 442 509, 296 445 743
Interests: Biocatalysis and biotransformation; immobilized microbial cells, their use in production and biotransformation of natural products; biotransformation of natural products by enzymes and microorganisms; preparation of glycosidases of microbial origin and their use for glycosylation of natural compounds: glycoconjugates, multivalent compounds, ergot alkaloids, flavonoids, antioxidants and chemoprotectants
Guest Editor
Prof. Dr. Maria Lourdes Gómez-Gómez

Botanical Institute. Section of Molecular Biology and Biotechnology. Pharmacy Faculty, Area of Genetics. University of Castilla-La Mancha, Campus Universitario s/n, 02071 Albacete, Spain
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Phone: (+34)-967-59-92-00
Fax: (+34)-967-59-92-33
Interests: plant biology and more specifically evolved around plant secondary metabolism; plant secondary metabolites, e.g. flavonols, isoflavonoids, anthocyanins, phenolic acids, carotenoids; biosynthetic pathways of plant natural products including secondary modifications (cleavage, glycosyations, methylations) and regulators; metabolic engineering from the production of valuable apocarotenoids in diverse crop species

Special Issue Information

Dear Colleagues,

Natural products (NP) have had a major impact on chemistry, chemical biology and drug discovery and have been part of medical remedies since ancient times. Nowadays, NP represent a unique source of leads for medicinal chemistry and drugs derived from NP have found widespread use for the treatment of cancer, cardiovascular diseases, bacterial and fungal infections. Numerous NP are either part of our current diet or are used as dietary supplements. NP are often targets of (relatively simple) derivatizations or transformation aiming often at the optimization of biological effects or preparation of metabolites. These targets are, however, extremely challenging due to complexity of the molecules, their sensitivity or their paucity. Respective transformations require highly selective, mild and high yielding approaches.

Topics for this Special Issue include the discovery of new methods, catalysts, and biocatalysts and the optimization of their functions. This Special Issue of IJMS will be interested in contributions that describe important new studies, which will broaden methodology of molecular transformation of natural products, such as carotenoids, flavonoids, alkaloids, natural glycosides and other NP. The methods should primarily reflect consecutive (biological) application of the products and, therefore should be oriented primarily (but not exclusively) to the green chemistry approaches.

Major requirements for papers submitted to this Special Issue are (i) clear novelty; (ii) reproducibility; (iii) molecular bases for reactions and processes; and (iv) defined chemical or biochemical reactions. Papers dealing with minor optimizations of known procedures, or those using poorly defined substrates, catalysts or biocatalysts that are unavailable to other researchers, and which contain poorly defined substrates and products, will be returned without further review.

Prof. Dr. Vladimír Křen
Prof. Dr. Maria Lourdes Gómez-Gómez
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural product

  • (bio)-catalyst development and design

  • natural product metabolites

  • carotenoid

  • flavonoid

  • green chemistry

  • encapsulation

Published Papers (11 papers)

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Research

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Open AccessArticle UDP-Glucose 4-Epimerase and β-1,4-Galactosyltransferase from the Oyster Magallana gigas as Valuable Biocatalysts for the Production of Galactosylated Products
Int. J. Mol. Sci. 2018, 19(6), 1600; https://doi.org/10.3390/ijms19061600
Received: 30 April 2018 / Revised: 23 May 2018 / Accepted: 24 May 2018 / Published: 29 May 2018
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Abstract
Uridine diphosphate galactose (UDP-galactose) is a valuable building block in the enzymatic synthesis of galactose-containing glycoconjugates. UDP-glucose 4-epimerase (UGE) is an enzyme which catalyzes the reversible conversion of abundantly available UDP-glucose to UDP-galactose. Herein, we described the cloning, expression, purification, and biochemical characterization
[...] Read more.
Uridine diphosphate galactose (UDP-galactose) is a valuable building block in the enzymatic synthesis of galactose-containing glycoconjugates. UDP-glucose 4-epimerase (UGE) is an enzyme which catalyzes the reversible conversion of abundantly available UDP-glucose to UDP-galactose. Herein, we described the cloning, expression, purification, and biochemical characterization of an unstudied UGE from the oyster Magallana gigas (MgUGE). Activity tests of recombinantly expressed MgUGE, using HPLC (high-performance liquid chromatography), mass spectrometry, and photometric assays, showed an optimal temperature of 16 °C, and reasonable thermal stability up to 37 °C. No metal ions were required for enzymatic activity. The simple nickel-affinity-purification procedure makes MgUGE a valuable biocatalyst for the synthesis of UDP-galactose from UDP-glucose. The biosynthetic potential of MgUGE was further exemplified in a coupled enzymatic reaction with an oyster-derived β-1,4-galactosyltransferase (MgGalT7), allowing the galactosylation of the model substrate para-nitrophenol xylose (pNP-xylose) using UDP-glucose as the starting material. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle Expression and Interaction Analysis among Saffron ALDHs and Crocetin Dialdehyde
Int. J. Mol. Sci. 2018, 19(5), 1409; https://doi.org/10.3390/ijms19051409
Received: 13 April 2018 / Revised: 3 May 2018 / Accepted: 7 May 2018 / Published: 9 May 2018
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Abstract
In saffron, the cleavage of zeaxanthin by means of CCD2 generates crocetin dialdehyde, which is then converted by an unknown aldehyde dehydrogenase to crocetin. A proteome from saffron stigma was released recently and, based on the expression pattern and correlation analyses, five aldehyde
[...] Read more.
In saffron, the cleavage of zeaxanthin by means of CCD2 generates crocetin dialdehyde, which is then converted by an unknown aldehyde dehydrogenase to crocetin. A proteome from saffron stigma was released recently and, based on the expression pattern and correlation analyses, five aldehyde dehydrogenases (ALDHs) were suggested as possible candidates to generate crocetin from crocetin dialdehydes. We selected four of the suggested ALDHs and analyzed their expression in different tissues, determined their activity over crocetin dialdehyde, and performed structure modeling and docking calculation to find their specificity. All the ALDHs were able to convert crocetin dialdehyde to crocetin, but two of them were stigma tissue-specific. Structure modeling and docking analyses revealed that, in all cases, there was a high coverage of residues in the models. All of them showed a very close conformation, indicated by the low root-mean-square deviation (RMSD) values of backbone atoms, which indicate a high similarity among them. However, low affinity between the enzymes and the crocetin dialdehyde were observed. Phylogenetic analysis and binding affinities calculations, including some ALDHs from Gardenia jasmonoides, Crocus sieberi, and Buddleja species that accumulate crocetin and Bixa orellana synthetizing the apocarotenoid bixin selected on their expression pattern matching with the accumulation of either crocins or bixin, pointed out that family 2 C4 members might be involved in the conversion of crocetin dialdehyde to crocetin with high specificity. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles
Int. J. Mol. Sci. 2018, 19(1), 81; https://doi.org/10.3390/ijms19010081
Received: 12 December 2017 / Revised: 21 December 2017 / Accepted: 22 December 2017 / Published: 28 December 2017
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Abstract
Stereoselective synthesis of monoterpene-based 1,2,4- and 1,3,4-oxadiazole derivatives was accomplished starting from α,β-unsaturated carboxylic acids, obtained by the oxidation of (−)-2-carene-3-aldehyde and commercially available (−)-myrtenal. 1,2,4-Oxadiazoles were prepared in two steps via the corresponding O-acylamidoxime intermediates, which then underwent cyclisation induced by
[...] Read more.
Stereoselective synthesis of monoterpene-based 1,2,4- and 1,3,4-oxadiazole derivatives was accomplished starting from α,β-unsaturated carboxylic acids, obtained by the oxidation of (−)-2-carene-3-aldehyde and commercially available (−)-myrtenal. 1,2,4-Oxadiazoles were prepared in two steps via the corresponding O-acylamidoxime intermediates, which then underwent cyclisation induced by tetrabutylammonium fluoride (TBAF) under mild reaction conditions. Stereoselective dihydroxylation in highly stereospecific reactions with the OsO4/NMO (N-methylmorpholine N-oxide) system produced α,β-dihydroxy 1,2,4-oxadiazoles. Pinane-based 1,3,4-oxadiazoles were obtained similarly from acids by coupling with acyl hydrazines followed by POCl3-mediated dehydrative ring closure. In the case of the arane counterpart, the rearrangement of the constrained carane system occurred with the loss of chirality under the same conditions. Stereoselective dihydroxylation with OsO4/NMO produced α,β-dihydroxy 1,3,4-oxadiazoles. The prepared diols were applied as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes. All compounds were screened in vitro for their antiproliferative effects against four malignant human adherent cell lines by means of the MTT assay with the O-acylated amidoxime intermediates exerting remarkable antiproliferative action. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle Evaluation of Biosynthesis, Accumulation and Antioxidant Activityof Vitamin E in Sweet Corn (Zea mays L.) during Kernel Development
Int. J. Mol. Sci. 2017, 18(12), 2780; https://doi.org/10.3390/ijms18122780
Received: 2 October 2017 / Revised: 9 December 2017 / Accepted: 11 December 2017 / Published: 20 December 2017
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Abstract
Sweet corn kernels were used in this research to study the dynamics of vitamin E, by evaluatingthe expression levels of genes involved in vitamin E synthesis, the accumulation of vitamin E, and the antioxidant activity during the different stage of kernel development. Results
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Sweet corn kernels were used in this research to study the dynamics of vitamin E, by evaluatingthe expression levels of genes involved in vitamin E synthesis, the accumulation of vitamin E, and the antioxidant activity during the different stage of kernel development. Results showed that expression levels of ZmHPT and ZmTC genes increased, whereas ZmTMT gene dramatically decreased during kernel development. The contents of all the types of vitamin E in sweet corn had a significant upward increase during kernel development, and reached the highest level at 30 days after pollination (DAP). Amongst the eight isomers of vitamin E, the content of γ-tocotrienol was the highest, and increased by 14.9 folds, followed by α-tocopherolwith an increase of 22 folds, and thecontents of isomers γ-tocopherol, α-tocotrienol, δ-tocopherol,δ-tocotrienol, and β-tocopherol were also followed during kernel development. The antioxidant activity of sweet corn during kernel development was increased, and was up to 101.8 ± 22.3 μmol of α-tocopherol equivlent/100 g in fresh weight (FW) at 30 DAP. There was a positive correlation between vitamin E contents and antioxidant activity in sweet corn during the kernel development, and a negative correlation between the expressions of ZmTMT gene and vitamin E contents. These results revealed the relations amongst the content of vitamin E isomers and the gene expression, vitamin E accumulation, and antioxidant activity. The study can provide a harvesting strategy for vitamin E bio-fortification in sweet corn. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors
Int. J. Mol. Sci. 2017, 18(12), 2704; https://doi.org/10.3390/ijms18122704
Received: 26 October 2017 / Revised: 1 December 2017 / Accepted: 8 December 2017 / Published: 13 December 2017
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Abstract
p38 Mitogen-activated protein kinase (p38 MAPK) is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this
[...] Read more.
p38 Mitogen-activated protein kinase (p38 MAPK) is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR) spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; −20 to −39) and several analogues with ΔE; −34 to −39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; −34 to −39) and in silico scores (Avg. score; −27.5 to −29.3). Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; −27.5 to −29.3) were found to inhibit p38 MAPK by 27–31% (p < 0.05) better than those with less scores (ΔE < −27.0). Especially, javamide-II-O-ethyl ester with relatively high in silico score (Avg. score; −29.2) inhibited p38 MAPK (IC50 = 9.9 μM) a little better than its methyl ester with best in silico score (Avg. score; −29.3). To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22–73% (p < 0.05) in the differentiated THP-1 cells, and the inhibition was slightly stronger by the ethyl ester than the methyl ester. Altogether, this study suggests that javamide-II-O-ethyl ester may be a most potent p38 MAPK inhibitor among the tested compounds and the combining in silico and in vitro assay approach may be a useful and efficient solution as a functional screening approach in searching new lead compounds for targeted molecules. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle Characterization of the Asiatic Acid Glucosyltransferase, UGT73AH1, Involved in Asiaticoside Biosynthesis in Centella asiatica (L.) Urban
Int. J. Mol. Sci. 2017, 18(12), 2630; https://doi.org/10.3390/ijms18122630
Received: 13 November 2017 / Revised: 30 November 2017 / Accepted: 1 December 2017 / Published: 6 December 2017
Cited by 1 | PDF Full-text (3230 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Centella asiatica (L.) Urban contains two ursane-type triterpene saponins, asiaticoside and madecassoside, as major secondary metabolites. In order to select candidate genes encoding UDP-glucosyltransferases (UGTs) involved in asiaticoside biosynthesis, we performed transcriptomic analysis of leaves elicited by methyl jasmonate (MeJA). Among the unigenes,
[...] Read more.
Centella asiatica (L.) Urban contains two ursane-type triterpene saponins, asiaticoside and madecassoside, as major secondary metabolites. In order to select candidate genes encoding UDP-glucosyltransferases (UGTs) involved in asiaticoside biosynthesis, we performed transcriptomic analysis of leaves elicited by methyl jasmonate (MeJA). Among the unigenes, 120 isotigs and 13 singletons of unique sequences were annotated as UGTs, including 37 putative full-length cDNAs, and 15 of the putative UGT genes were named according to the UGT committee nomenclature protocols. One of them, UGT73AH1, was characterized by heterologous expression in Escherichia coli BL21 (DE3) cells. After induction with IPTG, a total protein extract was assayed with UDP-glucose and asiatic acid. UPLC-QTOF/MS analysis showed that UGT73AH1 catalyzes the glycosylation of asiatic acid to its monoglucoside. It remains unclear whether glycosylation occurs on the triterpene C-2α, C-3β, C-23, or C-28 position. However, it is very likely that UGT73AH1 glucosylates the C-28 position, because only C-28 bears a glucose moiety in the final pathway product of asiatic acid, while C-2α, C-3β, and C-23 remain un-conjugated. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle The Silencing of Carotenoid β-Hydroxylases by RNA Interference in Different Maize Genetic Backgrounds Increases the β-Carotene Content of the Endosperm
Int. J. Mol. Sci. 2017, 18(12), 2515; https://doi.org/10.3390/ijms18122515
Received: 28 October 2017 / Revised: 15 November 2017 / Accepted: 16 November 2017 / Published: 24 November 2017
Cited by 2 | PDF Full-text (1807 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Maize (Zea mays L.) is a staple food in many parts of Africa, but the endosperm generally contains low levels of the pro-vitamin A carotenoid β-carotene, leading to vitamin A deficiency disease in populations relying on cereal-based diets. However, maize endosperm does
[...] Read more.
Maize (Zea mays L.) is a staple food in many parts of Africa, but the endosperm generally contains low levels of the pro-vitamin A carotenoid β-carotene, leading to vitamin A deficiency disease in populations relying on cereal-based diets. However, maize endosperm does accumulate high levels of other carotenoids, including zeaxanthin, which is derived from β-carotene via two hydroxylation reactions. Blocking these reactions could therefore improve the endosperm β-carotene content. Accordingly, we used RNA interference (RNAi) to silence the endogenous ZmBCH1 and ZmBCH2 genes, which encode two non-heme di-iron carotenoid β-hydroxylases. The genes were silenced in a range of maize genetic backgrounds by introgressing the RNAi cassette, allowing us to determine the impact of ZmBCH1/ZmBCH2 silencing in diverse hybrids. The β-carotene content of the endosperm increased substantially in all hybrids in which ZmBCH2 was silenced, regardless of whether or not ZmBCH1 was silenced simultaneously. However, the β-carotene content did not change significantly in C17 hybrids (M7 × C17 and M13 × C17) compared to C17 alone, because ZmBCH2 is already expressed at negligible levels in the C17 parent. Our data indicate that ZmBCH2 is primarily responsible for the conversion of β-carotene to zeaxanthin in maize endosperm. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle Two Cycloartenol Synthases for Phytosterol Biosynthesis in Polygala tenuifolia Willd
Int. J. Mol. Sci. 2017, 18(11), 2426; https://doi.org/10.3390/ijms18112426
Received: 22 October 2017 / Revised: 11 November 2017 / Accepted: 11 November 2017 / Published: 15 November 2017
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Abstract
Oxidosqualene cyclases (OSCs) are enzymes that play a key role in control of the biosynthesis of phytosterols and triterpene saponins. In order to uncover OSC genes from Polygala tenuifolia seedlings induced by methyl jasmonate (MeJA), RNA-sequencing analysis was performed using the Illumina sequencing
[...] Read more.
Oxidosqualene cyclases (OSCs) are enzymes that play a key role in control of the biosynthesis of phytosterols and triterpene saponins. In order to uncover OSC genes from Polygala tenuifolia seedlings induced by methyl jasmonate (MeJA), RNA-sequencing analysis was performed using the Illumina sequencing platform. A total of 148,488,632 high-quality reads from two samples (control and the MeJA treated) were generated. We screened genes related to phytosterol and triterpene saponin biosynthesis and analyzed the transcriptional changes of differentially expressed unigene (DEUG) values calculated by fragments per kilobase million (FPKM). In our datasets, two full-length cDNAs of putative OSC genes, PtCAS1, and PtCAS2, were found, in addition to the PtBS (β-amyrin synthase) gene reported in our previous studies and the two cycloartenol synthase genes of P. tenuifolia. All genes were isolated and characterized in yeast cells. The functional expression of the two PtCAS genes in yeast cells showed that the genes all produce a cycloartenol as the sole product. When qRT-PCR analysis from different tissues was performed, the expressions of PtCAS1 and PtCAS2 were highest in flowers and roots, respectively. After MeJA treatment, the transcripts of PtCAS1 and PtCAS2 genes increased by 1.5- and 2-fold, respectively. Given these results, we discuss the potential roles of the two PtCAS genes in relation to triterpenoid biosynthesis. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle Prebiotics Mediate Microbial Interactions in a Consortium of the Infant Gut Microbiome
Int. J. Mol. Sci. 2017, 18(10), 2095; https://doi.org/10.3390/ijms18102095
Received: 1 September 2017 / Revised: 28 September 2017 / Accepted: 2 October 2017 / Published: 4 October 2017
Cited by 2 | PDF Full-text (2026 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Composition of the gut microbiome is influenced by diet. Milk or formula oligosaccharides act as prebiotics, bioactives that promote the growth of beneficial gut microbes. The influence of prebiotics on microbial interactions is not well understood. Here we investigated the transformation of prebiotics
[...] Read more.
Composition of the gut microbiome is influenced by diet. Milk or formula oligosaccharides act as prebiotics, bioactives that promote the growth of beneficial gut microbes. The influence of prebiotics on microbial interactions is not well understood. Here we investigated the transformation of prebiotics by a consortium of four representative species of the infant gut microbiome, and how their interactions changed with dietary substrates. First, we optimized a culture medium resembling certain infant gut parameters. A consortium containing Bifidobacterium longum subsp. infantis, Bacteroides vulgatus, Escherichia coli and Lactobacillus acidophilus was grown on fructooligosaccharides (FOS) or 2′-fucosyllactose (2FL) in mono- or co-culture. While Bi. infantis and Ba. vulgatus dominated growth on 2FL, their combined growth was reduced. Besides, interaction coefficients indicated strong competition, especially on FOS. While FOS was rapidly consumed by the consortium, B. infantis was the only microbe displaying significant consumption of 2FL. Acid production by the consortium resembled the metabolism of microorganisms dominating growth in each substrate. Finally, the consortium was tested in a bioreactor, observing similar predominance but more pronounced acid production and substrate consumption. This study indicates that the chemical nature of prebiotics modulate microbial interactions in a consortium of infant gut species. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Open AccessArticle Synthesis and Antiradical Activity of Isoquercitrin Esters with Aromatic Acids and Their Homologues
Int. J. Mol. Sci. 2017, 18(5), 1074; https://doi.org/10.3390/ijms18051074
Received: 27 April 2017 / Revised: 12 May 2017 / Accepted: 13 May 2017 / Published: 17 May 2017
Cited by 3 | PDF Full-text (1754 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Isoquercitrin, (IQ, quercetin-3-O-β-d-glucopyranoside) is known for strong chemoprotectant activities. Acylation of flavonoid glucosides with carboxylic acids containing an aromatic ring brings entirely new properties to these compounds. Here, we describe the chemical and enzymatic synthesis of a series of
[...] Read more.
Isoquercitrin, (IQ, quercetin-3-O-β-d-glucopyranoside) is known for strong chemoprotectant activities. Acylation of flavonoid glucosides with carboxylic acids containing an aromatic ring brings entirely new properties to these compounds. Here, we describe the chemical and enzymatic synthesis of a series of IQ derivatives at the C-6″. IQ benzoate, phenylacetate, phenylpropanoate and cinnamate were prepared from respective vinyl esters using Novozym 435 (Lipase B from Candida antarctica immobilized on acrylic resin). The enzymatic procedure gave no products with “hydroxyaromatic” acids, their vinyl esters nor with their benzyl-protected forms. A chemical protection/deprotection method using Steglich reaction yielded IQ 4-hydroxybenzoate, vanillate and gallate. In case of p-coumaric, caffeic, and ferulic acid, the deprotection lead to the saturation of the double bonds at the phenylpropanoic moiety and yielded 4-hydroxy-, 3,4-dihydroxy- and 3-methoxy-4-hydroxy-phenylpropanoates. Reducing capacity of the cinnamate, gallate and 4-hydroxyphenylpropanoate towards Folin-Ciocalteau reagent was significantly lower than that of IQ, while other derivatives displayed slightly better or comparable capacity. Compared to isoquercitrin, most derivatives were less active in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, but they showed significantly better 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid, ABTS) scavenging activity and were substantially more active in the inhibition of tert-butylhydroperoxide induced lipid peroxidation of rat liver microsomes. The most active compounds were the hydroxyphenylpropanoates. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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Review

Jump to: Research

Open AccessReview Green Routes for the Production of Enantiopure Benzylisoquinoline Alkaloids
Int. J. Mol. Sci. 2017, 18(11), 2464; https://doi.org/10.3390/ijms18112464
Received: 6 November 2017 / Revised: 14 November 2017 / Accepted: 16 November 2017 / Published: 20 November 2017
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Abstract
Benzylisoquinoline alkaloids (BIAs) are among the most important plant secondary metabolites, in that they include a number of biologically active substances widely employed as pharmaceuticals. Isolation of BIAs from their natural sources is an expensive and time-consuming procedure as they accumulate in very
[...] Read more.
Benzylisoquinoline alkaloids (BIAs) are among the most important plant secondary metabolites, in that they include a number of biologically active substances widely employed as pharmaceuticals. Isolation of BIAs from their natural sources is an expensive and time-consuming procedure as they accumulate in very low levels in plant. Moreover, total synthesis is challenging due to the presence of stereogenic centers. In view of these considerations, green and scalable methods for BIA synthesis using fully enzymatic approaches are getting more and more attention. The aim of this paper is to review fully enzymatic strategies for producing the benzylisoquinoline central precursor, (S)-norcoclaurine and its derivatives. Specifically, we will detail the current status of synthesis of BIAs in microbial hosts as well as using isolated and recombinant enzymes. Full article
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
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