A gram scale synthesis of a multi-13C-labelled anthocyanin, [6,8,10,3′,5′-13C5]cyanidin-3-glucoside, for use in oral tracer studies in humans

Zhang, Qingzhi; Botting, Nigel P.; Kay, Colin D.

doi:10.1039/c1cc14323a

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…Production of 13 C-labelled anthocyanins by Vitis vinifera cell suspension cultures was demonstrated decades ago ( Krisa et al, 1999 ), but the system never went into commercial use. Recent studies on the pharmacokinetics of anthocyanins and their metabolites in humans ( Czank et al, 2013 , Ferrars et al, 2014 ) relied on chemical synthesis of the isotopically labelled anthocyanin, C3G ( Zhang et al, 2011 ). We have shown the suitability of our cell cultures for the 13 C-labelling of anthocyanins.…”

Section: Discussionmentioning

confidence: 99%

“…Full labelling of the anthocyanin backbone would require several rounds of media exchange until the cellular pool of 13 C-sucrose has reached equilibrium. To date, a maximum 13 C enrichment of 65% for anthocyanins from Vitis vinifera cell suspension cultures ( Krisa et al, 1999 ) and of nearly 100% for chemically synthesised 13 C 5 -C3G ( Zhang et al, 2011 ) have been reported. Against this background, our cell cultures present a valuable system for the production of defined isotopically labelled anthocyanins which can be used for bioavailability and degradation studies in humans.…”

Section: Discussionmentioning

confidence: 99%

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Colour bio-factories: Towards scale-up production of anthocyanins in plant cell cultures

Appelhagen

Wulff-Vester

Wendell

et al. 2018

Metabolic Engineering

102

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Anthocyanins are widely distributed, glycosylated, water-soluble plant pigments, which give many fruits and flowers their red, purple or blue colouration. Their beneficial effects in a dietary context have encouraged increasing use of anthocyanins as natural colourants in the food and cosmetic industries. However, the limited availability and diversity of anthocyanins commercially have initiated searches for alternative sources of these natural colourants. In plants, high-level production of secondary metabolites, such as anthocyanins, can be achieved by engineering of regulatory genes as well as genes encoding biosynthetic enzymes. We have used tobacco lines which constitutively produce high levels of cyanidin 3-O-rutinoside, delphinidin 3-O-rutinoside or a novel anthocyanin, acylated cyanidin 3-O-(coumaroyl) rutinoside to generate cell suspension cultures. The cell lines are stable in their production rates and superior to conventional plant cell cultures. Scale-up of anthocyanin production in small scale fermenters has been demonstrated. The cell cultures have also proven to be a suitable system for production of 13C-labelled anthocyanins. Our method for anthocyanin production is transferable to other plant species, such as Arabidopsis thaliana, demonstrating the potential of this approach for making a wide range of highly-decorated anthocyanins. The tobacco cell cultures represent a customisable and sustainable alternative to conventional anthocyanin production platforms and have considerable potential for use in industrial and medical applications of anthocyanins.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Colour bio-factories: Towards scale-up production of anthocyanins in plant cell cultures

Appelhagen

Wulff-Vester

Wendell

et al. 2018

Metabolic Engineering

102

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“…Isotope tracer studies have been very useful to establish the extent to which Cy3G is metabolized by splanchnic organs [94,105]. Czank et al [26] evaluated the post-prandial kinetics of 13 C 5 -Cy3G (500 mg) after intake.…”

Section: Foodomicsmentioning

confidence: 99%

Cyanidin-3-O-glucoside: Physical-Chemistry, Foodomics and Health Effects

et al. 2016

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Anthocyanins (ACNs) are plant secondary metabolites from the flavonoid family. Red to blue fruits are major dietary sources of ACNs (up to 1 g/100 g FW), being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed. Cy3G confers a red hue to fruits, but its content in raspberries and strawberries is low. It has a good radical scavenging capacity (RSC) against superoxide but not hydroxyl radicals, and its oxidative potential is pH-dependent (58 mV/pH unit). After intake, Cy3G can be metabolized (phases I, II) by oral epithelial cells, absorbed by the gastric epithelium (1%-10%) and it is gut-transformed (phase II & microbial metabolism), reaching the bloodstream (<1%) and urine (about 0.02%) in low amounts. In humans and Caco-2 cells, Cy3G's major metabolites are protocatechuic acid and phloroglucinaldehyde which are also subjected to entero-hepatic recycling, although caffeic acid and peonidin-3-glucoside seem to be strictly produced in the large bowel and renal tissues. Solid evidence supports Cy3G's bioactivity as DNA-RSC, gastro protective, anti-inflammatory, anti-thrombotic chemo-preventive and as an epigenetic factor, exerting protection against Helicobacter pylori infection, age-related diseases, type 2 diabetes, cardiovascular disease, metabolic syndrome and oral cancer. Most relevant mechanisms include RSC, epigenetic action, competitive protein-binding and enzyme inhibition. These and other novel aspects on Cy3G's physical-chemistry, foodomics, and health effects are discussed.

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“…To a flame-dried 100 mL round-bottom flask were added phloroglucinol 54 72 (1.00g, 4.13 mmol), followed by freshly distilled MeOH (41.0 mL). Benzaldehyde (421 μL, 4.13 mmol, 1.00 equiv), morpholine (361 μL, 4.13 mmol, 1.00 equiv), and triethylamine (576 μL, 4.13 mmol, 1.00 equiv) were then added successively via syringe and the reaction stirred at room temperature for 24 hours.…”

Section: Methodsmentioning

confidence: 99%

“…With the quaternary center secured, ketone 49 was converted to the corresponding dimethyl ketal 51 (Scheme 4a), a precursor to the dienophile for the o -QMHDA reaction ( vide infra ). While phenolic aldol conditions 28 failed to produce 16 , this acid-labile o- QM precursor was prepared from phloroglucinol 54 29 via the morpholine adduct ( 55 , Scheme 4b). 30 A control experiment determined that heating of 51 to 170 °C in toluene results in thermal extrusion of methanol to afford a 1:1 mixture of enol ethers 17 (Scheme 5).…”

Section: Design Plan: First Generation Strategymentioning

confidence: 99%

Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B

et al. 2018

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(+)-Psiguadial B is a diformyl phloroglucinol meroterpenoid that exhibits anti-proliferative activity against the HepG2 human hepatoma cancer cell line. This full account details the evolution of a strategy that culminated in the first enantioselective total synthesis of (+)-psiguadial B. A key feature of the synthesis is the construction of the trans-cyclobutane motif by a Wolff rearrangement with in situ catalytic, asymmetric trapping of the ketene. An investigation of the substrate scope of this method to prepare enantioenriched 8-aminoquinolinamides is disclosed. Three routes toward (+)-psiguadial B were evaluated that featured the following key steps: 1) an ortho-quinone methide hetero–Diels–Alder cycloaddition to prepare the chroman framework; 2) a Prins cyclization to form the bridging bicyclo[4.3.1]decane system, and 3) a modified Norrish–Yang cyclization to generate the chroman. Ultimately, the successful strategy employed a ring-closing metathesis to form the seven-membered ring and an intramolecular O-arylation reaction to complete the polycyclic framework of the natural product.

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A gram scale synthesis of a multi-13C-labelled anthocyanin, [6,8,10,3′,5′-13C5]cyanidin-3-glucoside, for use in oral tracer studies in humans

Cited by 18 publications

References 27 publications

Colour bio-factories: Towards scale-up production of anthocyanins in plant cell cultures

Colour bio-factories: Towards scale-up production of anthocyanins in plant cell cultures

Cyanidin-3-O-glucoside: Physical-Chemistry, Foodomics and Health Effects

Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B

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