Permethyl Ethers Research Articles

Total Syntheses of the Structures Assigned to Denigrins A, B, C, F, and G, 3,4-Diaryl-Pyrrole and -Pyrrolidinone Alkaloids, and the Conversion of Congener B into the Co-metabolite Spirodactylone.

The title marine natural products have been prepared by total synthesis and in the case of congeners 3, 6, and 7 for the first time. Each of these was obtained by manipulation of readily prepared denigrin B (2). The structure, 3, assigned to denigrin C is shown to be incorrect. Reaction of compound 2 with DDQ has led, in high yield, to the related natural product spirodactylone (16), while treating the corresponding permethyl ether 15 with PIFA/BF3·Et2O provides compound 20, embodying an isomeric framework.

Demethylative Lactonization Provides a Shortcut to High-Yielding Syntheses of Lamellarins.

Modular gram-scale syntheses of the trimethyl ethers of lamellarins G (6) and D (7) were achieved from readily accessible precursors in the highest overall yields reported to date (6, six steps, 82%; 7, seven steps, 86%). A novel demethylative lactonization between an aryl methyl ether and a neighboring carboxylic acid was developed for creating the chromenone unit of the targets to avoid the need for additional protection and deprotection steps. The central pyrrole core was constructed in a late-stage [4 + 1] condensation between ethyl bromoacetate and an enaminone possessing the remaining components of the lamellarin skeleton. Exhaustive demethylation of both permethyl ethers 6 and 7 gave the polyphenolic natural lamellarins A4 (3) and H (5), respectively.

Solving the supply of resveratrol tetramers from Papua New Guinean rainforest anisoptera species that inhibit bacterial type III secretion systems.

The supply of (-)-hopeaphenol (1) was achieved via enzymatic biotransformation in order to provide material for preclinical investigation. High-throughput screening of a prefractionated natural product library aimed to identify compounds that inhibit the bacterial virulence type III secretion system (T3SS) identified several fractions derived from two Papua New Guinean Anisoptera species, showing activity against Yersinia pseudotuberculosis outer proteins E and H (YopE and YopH). Bioassay-directed isolation from the leaves of A. thurifera, and similarly A. polyandra, resulted in three known resveratrol tetramers, (-)-hopeaphenol (1), vatalbinoside A (2), and vaticanol B (3). Compounds 1-3 displayed IC50 values of 8.8, 12.5, and 9.9 μM in a luminescent reporter-gene assay (YopE) and IC50 values of 2.9, 4.5, and 3.3 μM in an enzyme-based YopH assay, respectively, which suggested that they could potentially act against the T3SS in Yersinia. The structures of 1-3 were confirmed through a combination of spectrometric, chemical methods, and single-crystal X-ray structure determinations of the natural product 1 and the permethyl ether analogue of 3. The enzymatic hydrolysis of the β-glycoside 2 to the aglycone 1 was achieved through biotransformation using the endogenous leaf enzymes. This significantly enhanced the yield of the target bioactive natural product from 0.08% to 1.3% and facilitates ADMET studies of (-)-hopeaphenol (1).

Total synthesis of ochnaflavone

The first total syntheses of ochnaflavone, an asymmetric biflavone consisting of apigenin and luteolin moieties, and the permethyl ether of 2,3,2'',3''-tetrahydroochnaflavone have been achieved. The key steps in the synthesis of ochnaflavone were the formation of a diaryl ether and ring cyclization of an ether-linked dimeric chalcone to assemble the two flavone nuclei. Optimal experimental conditions for the oxidative cyclization to form ochnaflavone were established.

Total Synthesis of the Tolypothrix Pentaether from Enantiomerically Pure Homoallyl Alcohols by A Butyrolactone → 1,3‐Diol Strategy

AbstractFollowing the retrosynthetic plan of Scheme 1 the permethyl ether 1 from Tolypothrix conglutinata was synthesized from aldehyde 2 and the hydroxylated butyrolactone 3b. Each of these building blocks was obtained from a homoallyl alcohol, i. e. aldehyde 2 from homoallyl alcohol 5 (Scheme 3; 98.1% ee) and lactone 3b from homoallyl alcohol 30 (Schemes 10, 11; 97.7% ee). These alcohols, in turn, stemmed from the Ti(OEt)4/S‐BINOL‐mediated enantioselective addition of the β‐substituted stannane 7 to hexanal (Scheme 3) and the Ti(OEt)4/R‐BINOL‐mediated enantioselective addition of the β‐substituted stannane 31 to aldehyde 32 (Scheme 10), respectively. After O‐methylation of hydroxy lactone 3b (Scheme 11), the resulting methoxy lactone 38 was condensed with aldehyde 2 by Larson's modification of the Peterson olefination to provide the γ‐alkylidene lactone 39 as a 65:35 mixture of Z/E isomers (Scheme 12). Hydrogenation of this mixture gave the cis‐configured γ‐alkyl lactone 40 (Scheme 12). It was accompanied by no more than 5 mol‐% of its trans isomer; this observation seems to imply the occurrence of butenolide 41 as an intermediate of this reaction. An oxidative degradation of lactone 40 via the Criegee rearrangement of a derived peroxonosylate provided the syn‐diol 42 from where another three steps led to the target ether 1 (Scheme 13).

Pigments of fungi. Part 41. Synthesis of (S)-(+)- and (±)-dermolactone; stereochemistry of dermolactone from the Australian fungus Dermocybe sanguinea(Wulf. ex Fr.) Wünsche sensu Cleland

(S)-(+)-Dermolactone 3 has been synthesised in monochiral form beginning with ethyl (S)-lactate, the tetracyclic nucleus being assembled by way of a regiospecific cycloaddition between the known chloronaphthoquinone 15 and the novel, highly functionalised chiral butadiene derivative 5. Isochiral dermolactone 3+4 is prepared in the same way from (±)-5. Dermolactone, as it occurs naturally, is shown by 1H NMR shift experiments on the corresponding permethyl ethers 25 and 27, using [Eu(+)-(hfc)3], to consist of an anisochiral mixture of the (S)-(+)- and (R)-(–)-enantiomers 3 and 4, respectively, in which the former predominates in the ratio of 1.8:1 (28.6% ee).

Tetraflavonoids of Lophira alata

A new tetraflavonoid, lophiroflavan A, was isolated from the stem bark of Lophira alata along with lophirochalcone. Both compounds were obtained as their permethyl ether derivatives and their structures determined from spectroscopic and chemical evidence.

Products of estradiol/peroxidase interaction; Their structural features and biopolymeric character

Loss of tritium from [2,4,6α,7α- 3H]estradiol and from [2- 3H]estradiol during their conversion into polyestradiol (PEL) by horseradish peroxidase/H 2O 2 and the NMR spectrum of PEL permethyl ether suggest that PEL is composed of two or more different subunits, each formed by the joining of four molecules of estradiol with the loss of five hydrogen atoms from positions 2 and 4 and of three phenolic hydrogens leading to the formation of one C—C bond and three C—O bonds. At very low concentrations of estradiol the main reaction products were monomers; this is attributed to the initial formation of transient tetraestradiols which combine with water at high dilution and with themselves at low dilution. Association of the monomeric products to oligomers occurred on a Sephadex G-50 column and was readily reversed in phosphate buffer. In aqueous solution PEL underwent non-covalent changes induced by heat, time and electrolytes, and affecting its solubility, u.v. absorbance, extraction by organic solvents and ability to bind estradiol.

Antifungal activity of some new fiavones and fiavone glycosides of Echinops echinatus

Four phenolic compounds, viz., apigenin, apigenin-7-O-glucoside, echinacin, and echinaticin, were isolated from the whole plant of Echinops echinatus Roxb.; the latter two compounds were isolated for the first time. The two derivatives echinacin permethyl ether and apigenin-5,4′-dimethyl ether were obtained by methylation of echinacin and apigenin-7-O-glucoside permethylate, respectively. All the compounds were assayed against germination of conidia of Alternaria tenuissima (Kunz. ex Pers.) Wiltshire, which incites leaf blight disease in pigeon pea (Cajanus cajan (L.) Millsp.). All showed high efficacy against the pathogen at concentrations ranging from 25 to 150 μg mL−1. Echinacin, which was highly effective at 150 μg mL−1, is considered the most promising of these compounds and its use as a control measure against Alternaria blight of pigeon pea under field conditions has been suggested.

ＦＡＢＭＳにおける低極性有機化合物のための新しいマトリックス系の効果

A new matrix system m-NBA-DTDE (1:1) for FABMS of low-polar compounds, such as cholesterol (1) and stearic acid methyl ester (2), was prepared. The system, i.e., a 1:1 mixture of m-NBA (m-nitrobenzyl alcohol) to DTDE (2, 2′-dithiodiethanol or 2-hydroxyethyl disulfide), contributed to measuring the positive ion FAB mass spectra of above compounds and morusin permethyl ether (3), and it brought an effective result on the ion current lifetime and the reproducibility of their spectra. The positive ion FAB mass spectra of these low-polar compounds were compared with the corresponding positive ion EI and CI mass spectra.

Notizen: Neue Pulvinsäurederivate aus Pulveroboletus- Arten (Boletales)/ New Pulvinic Acid Derivatives from Pulveroboletus Species (Boletales)

Vulpinic acid has been isolated from sporophores of Pulveroboletus ravenelii, its first reported occurrence in a Basidiomycete. Permethyl ethers of methyl xerocomate and methyl atromentate and its corresponding monochloro derivatives are produced by P. auriflammeus of Japanese origin.

Structural determination of 6- C-diglycosyl-8- C-glycosyl-flavones and 6- C-glycosyl-8- C-diglycosylflavones by mass spectrometry of their permethyl ethers

Permethylated 6- C-diglycosyl-8- C-glycosylflavones and 6- C-glycosyl-8- C-diglycosylflavones gave well defined EIMS including the molecular peak and a fragmentation pattern characteristic of the 6- C-glycosyl residue. X″′- O-glycosides (8- C-disaccharides) are thus easily distinguished from X″- O-glycosides (6- C-disaccharides) and, in the latter, the position of the O-glycosidic bond should be deduced from the MS, after acid hydrolysis. Three new C-glycosylflavones have been characterized in this way from Spergularia rubra and Stellaria holostea.

Structural analysis of the neuraminic acid linkages in deaminated trisaccharide-alditols by gas-liquid chromatography-mass spectrometry

The separation and structural analysis of four deaminated sialotrisaccharide alditols as their permethyl ethers by gas-liquid chromatography (g.l.c.) and gas-liquid chromatography-mass spectrometry (g.l.c.-m.s.) is described. For the assignment of (2→3) and (2→6) linkages between sialic acid and d-galactose, trisaccharides having two different kinds of alditol units and also isotopic labelling of the sialic acid moiety have been used. The analysis by m.s. of the sialic acid moiety liberated is also presented. It is shown that the alditols may be separated from one another by g.l.c. with the SE-30 stationary phase. The position of the terminal glycosidic linkage may be established by m.s., without deuterium labelling of the molecule, in a similar way to that described for the corresponding alditols composed of simple hexoses. The use of g.l.c.-m.s. in studies of oligosaccharide mixtures produced by N-deacetylation and deamination of sialic acid-containing glycopeptides is discussed.

Determination of O-glycosidic bond position in 6- C-glycosylglucosylflavones by mass spectrometry

2″,3″,4″ and 6″- O-glycosides of 6- C-glucosylflavones can be differentiated by the MS of the hydrolysis products of their permethyl ethers.

Structural determination of C-glycosylflavones by mass spectrometry of their permethyl ethers: O-glycosyl-6- C-glycosylflavones

Permethylated O-glycosyl- C-glycosylflavones give well defined MS including an important molecular peak. Permethyl 6- C-glycosylflavones O-glycosylated on a phenolic hydroxyl group are easily distinguished from the isomeric permethyl 6- C-diholosylflavones. In both types, the position of the O-glycosidic bond can be deduced from the MS, eventually after acid hydrolysis. 2″- O-glycosyl-6- C-glycosylflavones can be differentiated from their 8- C isomers.

Identification of the glycosylflavones of Ephedra and Briza by mass spectrometry of their permethyl ethers

The application of permethylation and mass spectrometry to several glycoflavone samples homogenous by paper chromatography showed them in most cases to be mixtures of closely related isomers. A sample isolated from Ephedra andina leaves was identified by these means as a mixture of vicenin-1 and -2. Application of the procedure to a sample from Briza media thought to be vitexin showed it to be 8- C-galactosylapigenin and this was confirmed by co-chromatography with a synthetic specimen; an acylated 8- C-galactosylapigenin was also detected in the same source.

New norlignans of Sequoiadendron gigantea; phytochemical comparison with Sequoia sempervirens

The permethyl ethers of three new norlignans (sequirins-E, -F, and -G) from Sequoiadendron gigantea heartwood have been characterized by NMR and MS as 2-(3,4-dimethoxyphenyl)-4-(4-methoxyphenyl-, 2,4-(3,4-dimethoxyphenyl)-, and 2-(3,4-dimethoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-5-hydroxytetrahydropyran respectively, with the 2,5- trans,4,5- trans stereochemistry. Sequirins A-D, characteristic norlignans of Sequoia sempervirens Endl., could not be detected in S. gigantea heartwood, nor could sequirins E-G be found in S. sempervirens heartwood. Agatharesinol was a common constituent.

Structural determination of C-glycosylflavones by mass spectrometry of their permethyl ethers

Permethylated C-glycosylflavones give well defined MS, including in all cases an important molecular peak. The observed fragmentations are characteristic for the nature and position of the sugar. The 6- C and 8- C glycosylated derivatives are clearly differentiated. In dissymmetrical 6,8-di- C-glycosylflavones, the natures of the sugar in both the 6- and 8- positions can be determined. The structures of several natural compounds are discussed.

Partial methylation of methyl glycosides: A source of samples for analysis of methylation of carbohydrate-containing compounds

Methyl ether mixtures were obtained by partial methylation of 15 methyl glycopyranosides using Purdie's procedure. Identification of ethers as acetates by gas-liquid chromatography-mass spectroscopy (glc-ms) techniques allowed us to assume them to be sample sources for methylation analysis. T-values were tabulated using a scale ranging from permethyl ether- (0) to peracetate methyl glycosides (100) for subsequent identification with the aid of glc in NPGS and QF-1 liquid phases. A scheme has been devised for isolating individual methyl ethers by preparative glc.

Diosgenin saponins from Dioscorea floribunda

Five spirostanol glycosides and two furostanol glycosides were isolated from Dioscorea floribunda. In addition to the IR spectra of the free glycosides and the MS of the peracetates and permethyl ethers, the most effective method for structural determination proved to be the NMR spectra of the free saponins in pyridine- d 5.