Volubolin,a 4-phenyl-2H-1-benzopyran-2-one from Dalbergia volubilis

From the ether soluble portion of a methanolic extract of young non-green branches of Dalbergia volubilis, sitosterol, 7-hydroxy-4-methyl-2H-1-benz     

Synthesis of the 3- and 4-methyl, 3,4-dimethyl, and 3,4,6-trimethyl ethers of methyl 2-acetamido-2-deoxy-alpha-D-mannopyranoside

The methyl ethers of 2-amino-2-deoxy-D-mannose are reference compounds in studies, by the methylation procedure, of the chemical structure of polysaccharides containing 2-amino-2-deoxy-D-mannose and 2-amino-2-deoxy-D-mannuronic acid residues. Methylation of methyl 2-acetamido-2-deoxy-α-D-mannopyranoside (1) gave the 3,4,6-trimethyl ether. Methylation of the 6-trityl ether of 1, followed by detritylation, gave the 3,4-dimethyl ether of 1. Methylation of the 4,6-O-benzylidene derivative (6) of 1, followed by removal of the benzylidene group, gave the 3-methyl ether of 1. Benzoylation of 6, followed by removal of the benzylidene group and monobenzoylation, gave the 3,6-dibenzoate of 1, which was methylated, and the product saponified, to give the 4-methyl ether of 1; the latter compound was also obtained by a similar route via the 3-O-acetyl-6-O-benzoyl derivative.     

Allenic thioester hydration activity of beef liver crotonase

The conversion of 3-decynoyl-N-acetylcysteamine to 2,3-decadienoyl-N-acetylcysteamine catalyzed by a homogeneous mammalian liver enzyme has recently been described (F. M. Miesowicz and K. E. Bloch, Biochem. Biophys. Res. Commun.65, 331 (1975). The allenic thioester product, however, does not accumulate in crude liver extracts suggesting that it undergoes further enzymatic transformation. Evidence is presented here that crotonase (enoyl Coenzyme A hydratase) catalyzes the hydration of allenic thioesters to the corresponding β-keto thioesters which are normal intermediates in the β-oxidation of fatty acids.     

4-Hydroxydigitolutein,a new anthraquinone from callus tissue of Digitalis lanata

Many anthraquinone derivatives were isolated from the callus tissue of Digitalis lanata (Scrophulariaceae). Two of them were digitolutein (I) and a new anthraquinone 4-hydroxydigitolutein (II). The chemical structure of 4-hydroxydigitolutein was established to be 3-methylpurpurin 1-methyl ether by mass i.r. and NMR spectra and mixed melting point test with synthetic sample. Anthraquinone derivatives have been found for the first time in plant tissue cultures.     

Synthesis of lower chain allenic prostaglandins (1)

The synthesis of four lower chain allenic prostaglandin F_α analogues IXA-D is described.The allenyl moiety has only occasionally been incorporated into the prostanoid skeleton and in all the examples thus far reported ·(2,3), this functionality is located in the upper side chain at carbons 4–6. This communication describes the synthesis of four isomeric allenyl PGF_α derivatives wherein the cumulated diene system is situated at positions 13–15.     

Allenic germacranolides,bourbonene derived lactones and other constituents from Vernonia species

An investigation of seven Vernonia species, mainly from northern Brazil, afforded in addition to known compounds three new unusual sesquiterpene lactones with an allenic group. Intensive NMR studies fully established the structures. Furthermore, two lactones derived from bourbonene, two new glaucolides, a new furansesquiterpene, a nerolidol derivative and two other sesquiterpenes derived from eudesmane were isolated. The biogenetic relationships of the sesquiterpene lactones present in Veronia species as well as the chemotaxonomic aspects are discussed.     

Duartin,an isoflavan from Machaerium opacum

The heartwood of Machaerium opacum contains 2,3-dimethoxyphenol, the stilbenes pinosylvin monomethyl ether and dimethyl ether, and the isoflavans (?)-duartin and (?)-mucronulatol. The structure of (3S)-7,3′-dihydroxy-8,2′,4′-trimethoxyisoflavan was deduced for duartin and the constitution confirmed by synthesis of the racemate.     

Irreversible inactivation of mammalian Δ5-3β-hydroxysteroid dehydrogenases by 5, 10-secosteroids. Enzymatic oxidation of allenic alcohols to the corresponding allenic ketones

Novel 4,5-allenic 3β-hydroxy-5,10-secosteroids have been synthesized by sodium borohydride reduction of the corresponding conjugated allenic 3-oxo-5, 10-secosteroids. The secosteroid allenic alcohols are substrates for bovine adrenal and human placental Δ⁵-3β-hydroxysteroid dehydrogenases, and the resulting electrophilic conjugated allenic ketones are shown to inactivate these dehydrogenases in a time-dependent manner. Inactivated enzyme did not recover activity after filtration through Sephadex G-25. In contrast, the secosteroid allenic alcohols were not oxidized at C-3 by the bacterial 3β(and 17β)-hydroxysteroid dehydrogenase from $\text{P. testosteroni}$, nor did the corresponding allenic ketones inactivate this enzyme when incubated directly.     

Mechanism-based inhibitors of cytokinin oxidase/dehydrogenase attack FAD cofactor

Cytokinin oxidases/dehydrogenases (CKOs) mediate catabolic regulation of cytokinin levels in plants. Several substrate analogs containing an unsaturated side chain were studied for their possible inhibitory effect on maize CKO (ZmCKO1) by use of various bioanalytical methods. Two allenic derivatives, N⁶-(buta-2,3-dienyl)adenine (HA-8) and N⁶-(penta-2,3-dienyl)adenine (HA-1), were identified as strong mechanism-based inhibitors of the enzyme. Despite exhaustive dialysis, the enzyme remained inhibited. Conversely, substrate analogs with a triple bond in the side chain were much weaker inactivators. The crystal structures of recombinant ZmCKO1 complexed with HA-1 or HA-8 were solved to 1.95 Å resolution. Together with Raman spectra of the inactivated enzyme, it was revealed that reactive imine intermediates generated by oxidation of the allenic inhibitors covalently bind to the flavin adenine dinucleotide (FAD) cofactor. The binding occurs at the C4a atom of the isoalloxazine ring of FAD, the planarity of which is consequently disrupted. All the compounds under study were also analyzed for binding to the Arabidopsis cytokinin receptors AHK3 and AHK4 in a bacterial receptor assay and for cytokinin activity in the Amaranthus bioassay. HA-1 and HA-8 were found to be good receptor ligands with a significant cytokinin activity. Nevertheless, due to their ability to inactivate CKO in the desired time intervals or developmental stages, they both represent attractive compounds for physiological studies, as the inhibition mechanism of HA-1 and HA-8 is mainly FAD dependent.     

Conversion of amylose into a (1-4)-2-amino-2-deoxy-alpha-D-glucopyranuronan and its 2-N-sulfo derivative, a heparin analog

By a modification of a previously established reaction-sequence involving successive oxidation with methyl sulfoxide-acetic anhydride, oximation, and reduction with lithium aluminum hydride, 6-O-tritylamylose (1) was converted into a 6-O-tritylated (1→4)-α-D-linked glucan (3) containing 2-amino-2-deoxy-D-glucose residues and some O-(methylthio)methyl groups. Removal of the ether groups from this product gave a 2-aminated amylose (4) of degree of substitution (d.s.) by amine of 0.54 that underwent cleavage by fungal alpha-amylase to give oligosaccharides containing amino sugar residues. N-Trifluoroacetylation of 3 followed by removal of the ether groups, oxidation at C-6 with oxygen-platinum, and removal of the N-substituent, gave a (1 →4)-2-amino-2-deoxy-α-D-glucopyranuronan 7 having d.s. by amine of up to 0.65, and by carboxyl, of 0.46. Sulfation of this product with sulfur trioxide-pyridine and then with chlorosulfonic acid-pyridine gave a (1→4)-2-deoxy-2-sulfoamino-α-D-glucopyranuronan, isolated as its sodium salt 8, which showed appreciable blood-anticoagulant activity.     

A spectrophotometric assay for trans-cinnamic acid 4-hydroxylase activity.

trans-Cinnamic acid 4-hydroxylase (trans-cinnamic acid, NADPH: oxygen oxidoreductase [4-hydroxylating]) can be rapidly and precisely assayed by the spectrophotometric measurement of the production of 4-hydroxy-trans-cinnamic acid at 340 nm after acidification of the reaction mixture and subsequent readjustment to pH 11. For the assay of crude extracts and other preparations with high intrinsic absorption at 340 nm, the assay can be modified by extraction of the 4-hydroxy-trans-cinnamic acid from the acidified assay mixture through diethyl ether into alkali before spectrophotometric estimation. trans-Cinnamic acid 2-hydroxylase can be routinely detected and assayed in the same extract.     

3-Hydroxyisoflavanones from the stem bark of Dalbergia melanoxylon: Isolation,antimycobacterial evaluation and molecular docking studies

Two new 3-hydroxyisoflavanones, (S)-3,4′,5-trihydroxy-2′,7-dimethoxy-3′-prenylisoflavanone (trivial name kenusanone F 7-methyl ether) and (S)-3,5-dihydroxy-2′,7-dimethoxy-2″,2″-dimethylpyrano[5″,6″:3′,4′]isoflavanone (trivial name sophoronol-7-methyl ether) along with two known compounds (dalbergin and formononetin) were isolated from the stem bark of Dalbergia melanoxylon. The structures were elucidated using spectroscopic techniques. Kenusanone F 7-methyl ether showed activity against Mycobacterium tuberculosis, whereas both of the new compounds were inactive against the malaria parasite Plasmodium falciparum at 10 μg/ml. Docking studies showed that the new compounds kenusanone F 7-methyl ether and sophoronol-7-methyl ether have high affinity for the M. tuberculosis drug target INHA.     

Myricetin and quercetin methyl ethers from Haplopappus integerrimus var. Punctatus

Nine flavonoids including two new myricetin derivatives, myricetin 3′,4′-dimethyl ether and myricetin 3,3′, 4′-trimethyl ether, were obtained from Haplopappus integerrimus var. punctatus. The known compounds are quercetin 7,3′-dimethyl ether, querectin 3,3′-dimethyl ether, isorhamnetin, quercetin 3,7-dimethyl ether, quercetin 3-methyl ether, quercetin and quercetin 3-β-d-glucoside.     

Synthesis and contractile activity of new acetylenic and allenic analogues of leukotrienes C4 and D4: importance of the Z-11,12 double bond

The (5S,6R) isomers of new acetylenic and allenic analogues of leukotrienes C4 and D4 were synthesized for comparative pharmacological studies on intestinal smooth muscle preparations. These new analogues are poor spasmogenic agonists, the replacement of the 11,12-ene with a relatively more stable triple bond causing an important reduction in intrinsic activity. They did not show any significant antagonist activity. Unexpectedly, these results prove that the 11,12 portion in the triene structure of the lipophilic chain is critical for an agonist activity.     

Ether- and Ester-Bound iso-Diabolic Acid and Other Lipids in Members of Acidobacteria Subdivision 4

Recently, iso-diabolic acid (13,16-dimethyl octacosanedioic acid) has been identified as a major membrane-spanning lipid of subdivisions 1 and 3 of the Acidobacteria, a highly diverse phylum within the Bacteria. This finding pointed to the Acidobacteria as a potential source for the bacterial glycerol dialkyl glycerol tetraethers that occur ubiquitously in peat, soil, lakes, and hot springs. Here, we examined the lipid composition of seven phylogenetically divergent strains of subdivision 4 of the Acidobacteria, a bacterial group that is commonly encountered in soil. Acid hydrolysis of total cell material released iso-diabolic acid derivatives in substantial quantities (11 to 48% of all fatty acids). In contrast to subdivisions 1 and 3 of the Acidobacteria, 6 out of the 7 species of subdivision 4 (excepting “Candidatus Chloracidobacterium thermophilum”) contained iso-diabolic acid ether bound to a glycerol in larger fractional abundance than iso-diabolic acid itself. This is in agreement with the analysis of intact polar lipids (IPLs) by high-performance liquid chromatography-mass spectrometry (HPLC-MS), which showed the dominance of mixed ether-ester glycerides. iso-Diabolic acid-containing IPLs were not identified, because these IPLs are not released with a Bligh-Dyer extraction, as observed before when studying lipid compositions of subdivisions 1 and 3 of the Acidobacteria. The presence of ether bonds in the membrane lipids does not seem to be an adaptation to temperature, because the five mesophilic isolates contained a larger amount of ether lipids than the thermophile “Ca. Chloracidobacterium thermophilum.” Furthermore, experiments with Pyrinomonas methylaliphatogenes did not reveal a major influence of growth temperature over the 50 to 69°C range.     

Correlation of the content of hepatotoxin nodularin and glycosidic carotenoids, 4-ketomyxol-2′-fucoside and novel 1′-O-methyl-4-ketomyxol-2′-fucoside,in 20 strains of the cyanobacterium Nodularia spumigena

The carotenoids of 19 different strains of Nodularia spumigena and one Nodularia sphaerocarpa from different global locations were investigated. The molecular structure of the diagnostic pigment in N. spumigena of the Baltic Sea, tentatively named ‘4-keto-myxoxanthophyll-like pigment’ in Schlüter, L., Garde, K., Kaas, H., [2004. A 4-keto-myxoxanthophyll-like pigment is a diagnostic pigment for the toxic cyanobacteria Nodularia spumigena in the Baltic Sea. Mar. Ecol. Prog. Ser. 275, 69–78.] was determined to be a 4-ketomyxol-2′-fucoside. In most of the strains an additional carotenoid was found, identified as the novel 1′-O-methyl-4-ketomyxol-2′-fucoside by 2D NMR. This glycosidic carotenoid methyl ether was found to be a more important diagnostic pigment than the 4-ketomyxol-2′-fucoside for the toxic N. spumigena in the Baltic Sea. Out of the 20 strains 15 were found to produce the hepatotoxin nodularin. The content of carotenoids and nodularin was found to increase relative to chlorophyll a at increasing light intensity and at stationary growth, and nodularin was significantly correlated to both 4-ketomyxol-2′-fucoside and 1′-O-methyl-4-ketomyxol-2′-fucoside, and particular to the sum of these two pigments.     

Selective benzylation of some D-galactopyranosides. Unusual relative reactivity of the hydroxyl group at C-4

Partial benzylation of methyl 2,3-di-O-benzyl-α-D-galactopyranoside gave methyl 2,3,6-tri-O-benzyl-α-D-galactopyranoside as the major product, whereas the isomeric 2,6-di-O-benzyl ether gave a mixture of products in which the ratio of methyl 2,4,6- to methyl 2,3,6-tri-O-benzyl-α-D-galactopyranoside was ≈4:1. The proportion of unreacted starting-material was low in both cases, whereas after a similar reaction of methyl 2,6-di-O-benzyl-β-D-galactopyranoside more than 50% of the dibenzyl ether was recovered unchanged. In this case also, considerably higher reactivity was exhibited by the hydroxyl group at C-4 than that at C-3. Acid hydrolysis of the methyl glycosides of the tribenzyl ethers afforded crystalline 2,4,6-tri-O-benzyl-α-D-galactose and syrupy 2,3,6-tri-O-benzyl-D-galactose. Structures of intermediates were established by acetylation, examination of their n.m.r. spectra, and conversion into the known 3-O and 4-O-methyl-D-galactose.     

A new approach in exciton-coupled circular dichroism (ECCD)—insertion of an auxiliary stereogenic center

There are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane-1,4-diols (both ee or ea) and a wide variety of 3-hydroxy carotenoids, 3-hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROM? CH?C?CH-COOH. The allenic bond introduces a 90° twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases. © 1995 Wiley-Liss, Inc.     

Methylated Chalcones from Bidens torta

Four new natural products, all methylated chalcones, including an acetylated glycoside, were isolated from Bidens torta. Their structures were determined by spectroscopic methods as okanin 3,4,3′,4′-tetramethyl ether, okanin 3,4,3′-trimethyl ether 4′-glucoside, okanin 4-methyl ether 4′-glucoside and okanin 4-methyl ether 4′-glucoside monoacetate. Okanin 3,4-dimethyl ether 4′-glucoside was also isolated.     

Structural analysis by reductive cleavage with LiAlH4 of an allyl ether choline-phospholipid, archaetidylcholine, from the hyperthermophilic methanoarchaeon Methanopyrus kandleri

A choline-containing phospholipid (PL-4) in Methanopyrus kandleri cells was identified as archaetidylcholine, which has been described by Sprott et al. (1997). The PL-4 consisted of a variety of molecular species differing in hydrocarbon composition. Most of the PL-4 was acid-labile because of its allyl ether bond. The identity of PL-4 was confirmed by thin-layer chromatography followed by positive staining with Dragendorff reagent and fast-atom bombardment-mass spectrometry. A new method of LiAlH4 hydrogenolysis was developed to cleave allyl ether bonds and recover the corresponding hydrocarbons. We confirmed the validity of the LiAlH4 method in a study of the model compound synthetic unsaturated archaetidic acid (2,3-di-O-geranylgeranyl-sn-glycerol-1-phosphate). Saturated ether bonds were not cleaved by the LiAlH4 method. The hydrocarbons formed following LiAlH4 hydrogenolysis of PL-4 were identified by gas-liquid chromatography and mass spectrometry. Four kinds of hydrocarbons with one to four double bonds were detected: 47% of the hydrocarbons had four double bonds; 11% had three double bonds; 14% had two double bonds; 7% had one double bond; and 6% were saturated species. The molecular species composition of PL-4 was also estimated based on acid lability: 77% of the molecular species had two acid-labile hydrocarbons; 11% had one acid-labile and one acid-stable hydrocarbon; and 11% had two acid-stable hydrocarbons. To our knowledge, this is the first report of a specific chemical degradation method for the structural analysis of allyl ether phospholipid in archaea.