The curious yellow colouring matter of the Iceland poppy.

The pigment responsible for the yellow colour of the Iceland poppy (Papaver nudicaule) has fascinated chemists for decades. Named nudicaulin by Sir Robert Robinson in 1939, this flavoalkaloid has been the subject of several structural elucidation, biosynthesis, total synthesis and chemical ecology investigations. This account provides a chronological overview of the fascinating history of this natural product.

Stereodivergent, Chemoenzymatic Synthesis of Azaphilone Natural Products.

Selective access to a targeted isomer is often critical in the synthesis of biologically active molecules. Whereas small-molecule reagents and catalysts often act with anticipated site- and stereoselectivity, this predictability does not extend to enzymes. Further, the lack of access to catalysts that provide complementary selectivity creates a challenge in the application of biocatalysis in synthesis. Here, we report an approach for accessing biocatalysts with complementary selectivity that is orthogonal to protein engineering. Through the use of a sequence similarity network (SSN), a number of sequences were selected, and the corresponding biocatalysts were evaluated for reactivity and selectivity. With a number of biocatalysts identified that operate with complementary site- and stereoselectivity, these catalysts were employed in the stereodivergent, chemoenzymatic synthesis of azaphilone natural products. Specifically, the first syntheses of trichoflectin, deflectin-1a, and lunatoic acid A were achieved. In addition, chemoenzymatic syntheses of these azaphilones supplied enantioenriched material for reassignment of the absolute configuration of trichoflectin and deflectin-1a based on optical rotation, CD spectra, and X-ray crystallography.

Biomimetic synthesis of nudicaulins I and II, yellow pigments from the Iceland poppy Papaver nudicaule.

Indole and the anthocyanin orientalin proceed through a unique cascade sequence that leads to nudicaulins I and II in 92% yield. This biomimetic synthesis confirms the biosynthesis proposal for these structurally unprecedented flavoalkaloids that play a key role in the colour range displayed by the Iceland poppy.

Redshifted and Near-infrared Active Analog Pigments Based upon Archaerhodopsin-3.

Archaerhodopsin-3 (AR3) is a member of the microbial rhodopsin family of hepta-helical transmembrane proteins, containing a covalently bound molecule of all-trans retinal as a chromophore. It displays an absorbance band in the visible region of the solar spectrum (λmax 556 nm) and functions as a light-driven proton pump in the archaeon Halorubrum sodomense. AR3 and its mutants are widely used in neuroscience as optogenetic neural silencers and in particular as fluorescent indicators of transmembrane potential. In this study, we investigated the effect of analogs of the native ligand all-trans retinal A1 on the spectral properties and proton-pumping activity of AR3 and its single mutant AR3 (F229S). While, surprisingly, the 3-methoxyretinal A2 analog did not redshift the absorbance maximum of AR3, the analogs retinal A2 and 3-methylamino-16-nor-1,2,3,4-didehydroretinal (MMAR) did generate active redshifted AR3 pigments. The MMAR analog pigments could even be activated by near-infrared light. Furthermore, the MMAR pigments showed strongly enhanced fluorescence with an emission band in the near-infrared peaking around 815 nm. We anticipate that the AR3 pigments generated in this study have widespread potential for near-infrared exploitation as fluorescent voltage-gated sensors in optogenetics and artificial leafs and as proton pumps in bioenergy-based applications.

Total Synthesis of Carthamin, a Traditional Natural Red Pigment.

The first total synthesis of carthamin (3), a historic natural red pigment, has been achieved. The molecular structure was efficiently constructed by assembling two equivalents of the in situ generated lithiated monomers and triisopropyl orthoformate. This synthesis confirms the structure proposed in 1996.

Solid-phase extraction using octadecyl-bonded silica modified with photosynthetic pigments from Spinacia oleracea L. for the preconcentration of lead(II) ions from aqueous samples.

Spinacia oleracea L. extract was immobilized on an octadecyl-bonded silica surface to produce a new sorbent for the solid-phase extraction of trace amounts of metal ions from aqueous neutral samples. A measurement of the metal content has been performed by using graphite furnace atomic absorption spectroscopy. The affinity of the investigated bivalent metal cations for the modified sorbent are in the order: Pb(II) > Cu(II) > Ni(II) > Zn(II) ≈ Cd(II) ≈ Co(II). The quantum-chemically calculated chlorophyll-a-metal ion binding energies were consistent with the measured affinities of the corresponding metal ions to the investigated sorbent. The maximum sorption capacity obtained for Pb(II) was equal to 1.44 µmol/g. The value of lead uptake was significantly higher in comparison to the one reported for other sorbents and biosorbents. Immobilized chlorophyll a is responsible for a chelation process with stoichiometry 1:1 owing to the porphyrin rings, which was confirmed by the quantitative analysis performed by reversed-phase high-performance liquid chromatography with diode array detection. The Toth adsorption isotherm model was applicable to the description of the adsorption process of either chlorophyll a or Pb(II). The structural analysis of sorbent was done using Fourier-transform Raman spectroscopy and scanning electron microscopy with an energy dispersive X-ray detector.

Structural Color for Additive Manufacturing: 3D-Printed Photonic Crystals from Block Copolymers.

The incorporation of structural color into 3D printed parts is reported, presenting an alternative to the need for pigments or dyes for colored parts produced through additive manufacturing. Thermoplastic build materials composed of dendritic block copolymers were designed, synthesized, and used to additively manufacture plastic parts exhibiting structural color. The reflection properties of the photonic crystals arise from the periodic nanostructure formed through block copolymer self-assembly during polymer processing. The wavelength of reflected light could be tuned across the visible spectrum by synthetically controlling the block copolymer molecular weight and manufacture parts that reflected violet, green, or orange light with the capacity to serve as selective optical filters and light guides.

Preparative Synthesis of Spinochrome D, a Pigment of Different Sea Urchin Species.

A simple and effective synthesis of spinochrome D (1) (2,3,5,6,8-pentahydroxy-1,4-naphthoquinone), a pigment of different sea urchin species, has been developed starting from 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (13), easily available by cycloacylation of 1,4-dimethoxybenzene (11) with dichloromaleic anhydride (12). Bromination of 13 with either bromine or dioxane dibromide to 6-bromo-2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (21), followed by nucleophilic substitution of the halogen atoms by methoxy groups in 21 and hydrolysis of trimethyl ether 10 produce the target compound in overall yield from 62 to 65%.

Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro.

The aggregation of the microtubule-associated protein tau is a seminal event in many neurodegenerative diseases, including Alzheimer's disease. The inhibition or reversal of tau aggregation is therefore a potential therapeutic strategy for these diseases. Fungal natural products have proven to be a rich source of useful compounds having wide varieties of biological activities. We have previously screened Aspergillus nidulans secondary metabolites for their ability to inhibit tau aggregation in vitro using an arachidonic acid polymerization protocol. One aggregation inhibitor identified was asperbenzaldehyde, an intermediate in azaphilone biosynthesis. We therefore tested 11 azaphilone derivatives to determine their tau assembly inhibition properties in vitro. All compounds tested inhibited tau filament assembly to some extent, and four of the 11 compounds had the advantageous property of disassembling preformed tau aggregates in a dose-dependent fashion. The addition of these compounds to the tau aggregates reduced both the total length and number of tau polymers. The most potent compounds were tested in in vitro reactions to determine whether they interfere with tau's normal function of stabilizing microtubules (MTs). We found that they did not completely inhibit MT assembly in the presence of tau. These derivatives are very promising lead compounds for tau aggregation inhibitors and, more excitingly, for compounds that can disassemble pre-existing tau filaments. They also represent a new class of anti-tau aggregation compounds with a novel structural scaffold.

One-step synthesis of betalains using a novel betalamic acid derivatized support.

Betalains are plant pigments with high antioxidant and cancer chemopreventive properties used by the food industry as safe colorants. Betalains are restricted to species of the order Caryophyllales, and difficulty in obtaining individual molecules has limited their structural identification and application. This study was designed to develop a betalamic acid derivatized support generated from a primary amine polymer. The novel material presents color properties of a pseudobetaxanthin, and it is stable for at least 6 months. The bond formed can be displaced at mild conditions by the addition of amines in aqueous solutions over a broad pH range and at 25 °C. This releases the betalamic acid while forming the corresponding pigment. This one-step procedure significantly simplifies the process of obtaining semisynthetic betalains, and it is optimized here for the formation of betaxanthins and betacyanins derived from tyramine, dopamine, pyrrolidine, and indoline. The new method makes access to single betalains available to the entire scientific community and could stimulate research and applications in the field.

Abiotic photophosphorylation model based on abiogenic flavin and pteridine pigments.

A model for abiotic photophosphorylation of adenosine diphosphate by orthophosphate with the formation of adenosine triphosphate was studied. The model was based on the photochemical activity of the abiogenic conjugates of pigments with the polymeric material formed after thermolysis of amino acid mixtures. The pigments formed showed different fluorescence parameters depending on the composition of the mixture of amino acid precursors. Thermolysis of the mixture of glutamic acid, glycine, and lysine (8:3:1) resulted in a predominant formation of a pigment fraction which had the fluorescence maximum at 525 nm and the excitation band maxima at 260, 375, and 450 nm and was identified as flavin. When glycine in the initial mixture was replaced with alanine, a product formed whose fluorescence parameters were typical to pteridines (excitation maximum at 350 nm, emission maximum at 440 nm). When irradiated with the quasi-monochromatic light (over the range 325-525 nm), microspheres in which flavin pigments were prevailing showed a maximum photophosphorylating activity at 375 and 450 nm, and pteridine-containing chromoproteinoid microspheres were most active at 350 nm. The positions and the relative height of maxima in the action spectra correlate with those in the excitation spectra of the pigments, which point to the involvement of abiogenic flavins and pteridines in photophosphorylation.

Concise synthesis of flavocommelin, 7-O-methylapigenin 6-C-, 4'-O-bis-ß-D-glucoside, a component of the blue supramolecular pigment from Commelina communis.

Flavocommelin, 7-O-methylapigenin 6-C-, 4'-O-bis-ß-D-glucoside, was synthesized in 9 steps from the C-glycosylation of 6-O-benzy-4-O-methylphloroacetophenone via the introduction of a cinnamoyl residue by aldol condensation and the formation of a C-ring by regioselective and oxidative ring-closure to regio- and stereoselective O-glycosylation for an overall yield of 31%.

Synthesis and structural characterization of oaklin-catechins.

Condensation reactions of procyanidin dimer B4 with two representative oak wood cinnamic aldehydes (coniferaldehyde and sinapaldehyde) were conducted in winelike model solutions. Coniferaldehyde led to the formation of guaiacylcatechin-pyrylium-catechin (GCP-catechin, 737 m/z), whereas sinapaldehyde led to the formation of syringylcatechin-pyrylium-catechin (SCP-catechin, 767 m/z). The former was also structurally characterized by 1D and 2D NMR, allowing an elucidation of the formation mechanism of these oaklin-catechin adducts and demonstrating the importance of procyanidins in the formation of colored compounds through the reaction with cinnamic aldehydes extracted from oaks during storage.

[Comparative structural and functional characteristics of different forms of Saccharomyces cerevisiae red pigment and its synthetic analogue].

Structural and functional characteristics of the yeast red pigment (product of polymerization of N1-(beta-D-ribofuranosyl)-5-aminoimadazole), isolated from adel 1 mutant cells of Saccharomyces cerevisiae, its deribosylated derivatives (obtained by acid hydrolysis) and its synthetic pigment analogue (product of polymerization of N1-methyl-5-aminoimadazole in vitro) has been obtained. Products of in vitro polymerization were identified using mass spectrometry. The ability of these pigments to inhibit amyloid formation using insulin fibrils was compared. The entire compounds studied were able to interact with amyloids and inhibit their growth. Electron and atomic force microscopy revealed a common feature inherent in the insulin fibrils formed in presence of these compounds--they were merged into conglomerates that were more stable and resistant to the effects of ultrasound in comparison with insulin aggregates grown without pigments. We speculate that all these compounds can cause coalescence of fibrils, partially block their loose ends and, thereby, inhibit the attachment of new monomers to growing fibrils.

Columnar mesophases based on zinc chlorophyll derivatives functionalized with peripheral dendron wedges.

A chlorophyll derivative with a central zinc ion, a methoxy functionality at its 3(1)-position, and functionalized with a second-generation dendron (3,4-3,4,5)12G2-CH(2)OH at its 17(2)-position was synthesized starting from natural chlorophyll a (Chl a). This compound exhibits liquid crystalline (LC) behavior and its mesomorphic properties have been characterized by differential scanning calorimetry (DSC), polarisation optical microscopy (POM), powder X-ray diffraction (XRD), and scanning probe microscopy (SPM). A combination of powder XRD, high resolution scanning tunneling microscopy (STM), and atomic force microscopy (AFM) experiments revealed the formation of nano-segregated well-ordered columnar tubular superstructures consisting of about five molecules in the column stratum. These self-assembled columns are further self-organized into a two-dimensional oblique unit cell lattice. Semiconducting behavior of this compound has been studied by pulse-radiolysis time-resolved microwave conductivity (PR-TRMC) method and charge carrier mobility values of ∼10(-2) cm(2) V(-1) s(-1) are observed. Such organized columnar superstructures constructed from semisynthetic zinc chlorins are reminiscent of the tubular organization of the bacteriochlorophyll dyes in the light-harvesting chlorosomal antennae of green sulphur bacteria.

Short and regiospecific synthesis of echinamine A--the pigment of sea urchin Scaphechinus mirabilis.

New convenient two-step synthesis of natural pigment echinamine A by the condensation of 2,3-dichloro-6-ethyl-7-hydroxy-1,4-naphthoquinone with sodium nitrite and subsequent reduction of intermediate 7-ethyl-2,5,6,8-tetrahydroxy-3-nitro-1,4-naphthoquinone has been developed.

Leaf anatomy affects the extraction of photosynthetic pigments by DMSO.

Dimethylsulfoxide (DMSO) is a widely used solvent for the extraction of chlorophylls (Chls) from leaves of higher plants. The method is preferred because the time-consuming steps of grinding and centrifuging are not required and the extracts are stable for a long time period. However, the extraction efficiency of this solvent is not comparable among plant species, whereas the particular leaf anatomical characteristics responsible for this unevenness remain unknown. In order to examine the influence of leaf anatomy on the extraction efficiency of DMSO (i.e. the concentration of Chls extracted with DMSO as % of the concentration of Chls extracted with 80% acetone), leaves of 19 plant species with different anatomical characteristics were incubated for 40min in DMSO at 65 degrees C. Under these conditions, heterobaric leaves, which are characterized by the occurrence of bundle sheath extensions in the mesophyll, showed lower extraction efficiency of DMSO compared to homobaric leaves and conifer needles. Microscopical observations of DMSO incubated leaf tissues showed that bundle sheath extensions behave as anatomical barriers which prevent the diffusion of DMSO within heterobaric leaves, even after prolonged incubation with the solvent. The effect was stronger in heterobaric leaves possessing thick bundle sheath extensions. The extraction efficiency of DMSO in these leaves was improved by vacuum infiltration of the samples in the presence of warm (65 degrees C) solvent.

Total synthesis of chlorofusin, its seven chromophore diastereomers, and key partial structures.

Chlorofusin is a recently isolated, naturally occurring inhibitor of p53-MDM2 complex formation whose structure is composed of a densely functionalized azaphilone-derived chromophore linked through the terminal amine of ornithine to a nine residue cyclic peptide. Herein we report the full details of the total synthesis of chlorofusin, resulting in the assignment of the absolute stereochemistry and reassignment of the relative stereochemistry of the complex chromophore. Condensation of each enantiomer of an azaphilone chromophore precursor with the N(delta)-amine of a protected ornithine-threonine dipeptide, followed by a one-step oxidation/spirocyclization of the most reactive olefin provided all eight diastereomers of the fully elaborated chromophore-dipeptide conjugate. Comparison of the spectroscopic properties for these eight compounds and those of simpler models with that reported for the natural product allowed the full assignment of the (4R,8S,9R)-stereochemistry of the chlorofusin chromophore. The natural, but stereochemically reassigned, diastereomer of the dipeptide conjugate was incorporated in a convergent total synthesis of chlorofusin confirming the stereochemical reassignment and establishing its absolute stereochemistry. Similarly and enlisting the late stage convergent point in the total synthesis, the remaining seven diastereomers of the chromophore-dipeptide conjugates were individually incorporated into the nine-residue cyclic peptide of chlorofusin (4 steps each) providing all seven remaining possible chromophore diastereomers of the natural product.

Asymmetric syntheses of (-)-mitorubrin and related azaphilone natural products.

Asymmetric syntheses of (-)-mitorubrin and related azaphilone natural products are reported. Key steps involve copper-mediated, enantioselective oxidative dearomatization to prepare the azaphilone core and olefin cross-metathesis for side-chain installation. [reaction: see text]