Synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one from a pyranulose glycoside.

The synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one (9) is described. Treatment of pyranulose glycoside with bromine in carbon tetrachloride afforded brompyranulose glycoside in 90% yield. The reaction of (6S)- and (6R)-4-bromo-6-hydroxy-6-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-6H- pyran-3-one (2) in acidic media was examined with the following results: the reaction of 2 with trifluoroacetic acid (TFA) in dioxane afforded a mixture of 5-hydroxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (3) and its furan derivative 5-hydroxy-2-{5-(benzoyloxy)methyl]furan-2-yl}pyran-4-one (4), but the use of hydrochloric acid formed the bromofurfural, 3-bromo-5-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-2-furancarboxyal dehyde only. Acetylation of a mixture (3 and 4) with acetic anhydride facilitated product separation to give the corresponding acetates 5-acetoxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (5) and 5-acetoxy-2-{5-[(benzoyloxy)methyl]furan-2-yl}pyran-4-one (6). Treatment of 5 with hydrazine afforded 3-hydroxymethyl-6-(beta-D-ribofuranosyl)-1H-pyridazin-4-one in 43% yield. Debenzoylation of 5 with aq ammonia gave 9 in 50% yield.     

Synthesis of fluorinated 3β-hydroxypregn-5-en-20-one derivatives

Treatment of the unstable 3β-hydroxy-20, 20-dimethoxypregn-5-ene 3-acetate with acetic anhydride at reflux temperature gave a mixture of 3β-hydroxy-20-methoxypregna-5, 17(20)-diene and 3β-hydroxy-20-methoxypregna-5, 20-diene 3-acetates. Fluorination of this mixture with perchloryl fluoride afforded after fractionated crystallization 3β-hydroxy-17-fluoro-20-methoxypregna-5, 20-diene 3-acetate. Acid hydrolysis of the reaction mixture and subsequent Chromatographic separation led to 3β-hydroxy-17-fluoropregn-5-en-20-one 3-acetate and 3β-hydroxy-21-fluoropregn-5-en-20-one 3-acetate. 3β-Hydroxy-17-fluoro-20-methoxypregna-5, 20-diene 3-acetate did not react further with perchloryl fluoride even under forcing conditions. Fluorination of 3β-hydroxy-20-(N-ethyl benzylamino)-pregna-5, 17(20)-diene gave 3β-hydroxy-17, 21-difluoro-pregn-5-en-20-one, exclusively.     

Synthesis and Antimicrobial Activity of Some New Coumarin and Dicoumarol Derivatives

Russian Journal of Bioorganic Chemistry - Phase transfer catalysis reaction of 4-hydroxy-6-methyl-2H-chromen-2-one with alkyl halides afforded C4 oxygen alkylation products of 2H-chromen-2-one...     

Synthesis of deuterium-labeled 17-hydroxyprogesterone suitable as an internal standard for isotope dilution mass spectrometry

A synthesis is reported of 17-hydroxyprogesterone, labeled with four atoms of deuterium at ring C and suitable for use as an internal standard for isotope dilution mass spectrometry. Base-catalyzed equilibration of methyl 3 alpha-acetoxy-12-oxo-cholanate (III) with 2H2O, followed by reduction of the 12-oxo group by the modified Wolff-Kisher method using [2H]diethylene glycol and [2H]hydrazine hydrate afforded [11,11,12,12,23,23(-2)H]lithocholic acid (V). The Meystre-Miescher degradation of the side chain of V yielded 3 alpha-hydroxy-5 beta-[11,11,12,12(-2)H]pregnan-20-one (X). Oxidation of the 3,20-enol-diacetate of X with perbenzoic acid followed by saponification afforded 3 alpha,17-dihydroxy-5 beta-[11,11,12,12(-2)H]pregnan-20-one (XI). Oxidation of XI with N-bromoacetamide yielded 17-hydroxy-5 beta-[11,11,12,12(-2)H]pregnane-3,20-dione (XII). Bromination of XII followed by dehydrobromination yielded 17-hydroxy-[11,11,12,12(-2)H] progesterone (XIV), consisting of 0.3% 2H0-, 1.1% 2H1-, 8.6% 2H2-, 37.1% 2H3-, 52.1% 2H4-, and 0.8% 2H5-species.     

Diarylheptanoids from the rhizomes of Zingiber officinale

Seven new diarylheptanoids, i.e., (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3-acetoxy-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxy-5-methoxy-phenyl)heptan-3-one and 1,5-epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane were isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe), along with 25 known compounds, i.e., 8 diarylheptanoids, 14 gingerol analogs, a diterpene and 2 steroids. Their structures were elucidated by spectroscopic and chemical methods.     

Homoisoflavonoids and stilbenes from the bulbs of Scilla nervosa subsp. rigidifolia

Thirteen homoisoflavonoids, nine of which are new: 3-(4-methoxybenzyl)-5,7-dimethoxychroman-4-one, 3-(4-hydroxy-3-methoxybenzyl)-5-hydroxy-7-methoxychroman-4-one, 3-(4-methoxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one, 3-(4-hydroxybenzylidene)-5-hydroxy-7-methoxychroman-4-one, 3-(4-hydroxy-3-methoxybenzyl)-5-hydroxy-6,7-dimethoxychroman-4-one, 3-(3,4-dimethoxybenzyl)-5,7-dihydroxychroman-4-one, 3-(4-methoxybenzyl)-6-hydroxy-5,7-dimethoxychroman-4-one, 3-(4-hydroxybenzyl)-5,6,7-trimethoxychroman-4-one and 3-(4-methoxybenzyl)-8-hydroxy-5,7-dimethoxychroman-4-one, were isolated from the bulbs of Scilla nervosa together with four known ones and three known stilbene derivatives. The structures of these secondary metabolites were characterized by spectroscopic means and by comparison with published information for known compounds.     

Preparative Biorganic Chemistry Part 10 Asymmetric Reduction of Bicyclo[2.2.2]Octane-2,6-Diones with Baker's Yeast

Reduction of bicyclo[2.2.2]octane-2,6-dione with baker's yeast gave (lR,4S,6S)-6-hydroxybi-cyclo[2.2.2]octan-2-one (95% e.e.) contaminated with 8% of its (1S,4R,6S)-isomer. Similarly, the yeast reduction of 1-methylbicyclo[2.2.2]octane-2,6-dione furnished (1R,4S,6S)-6-hydroxy-1-methylbi-cyclo[2.2.2.]octan-2-one (99.5% e.e.) in 59% yield. The yeast reduction of 4-methylbi-cyclo[2.2.2.]octane-2,6-dione afforded (1R,4S,6S)-6-hydroxy-4-methylbicyclo[2.2.2.]octan-2-one (98% e.e.) contaminated with 3% of its (1S,4R,6S)-isomer in 58% yield.     

New phenolic inhibitors of the peroxidse-catalysed oxidation of indole-3-acetic acid

Previously we reported two metabolites of the insecticide carbofuran as persistent inhibitors of the peroxidase-catalysed oxidtion ofindole-3-acetic acid. In searching for more active inhibitors of this type, we have found that 5-hydroxy-2,2-dimethylchromene (β-tubanol), 2′,6′-dihydroxycetophenone oxime, 5-hydroxy-2,2-dimethylchroman, 2′,6′-dihydroxyacetophenone and 2,6-dihydroxybenzoic acid methyl ester were more active than the carbofuran metabolite 7-hydroxy-2,2-dimethyl-3-oxo-2,3-dihydrobenzofuran. Resorcinol, 5-hydroxy-2,2-dimethylchroman-4-one, 3-hydroxy-5-methoxy-2,2-dimethylchroman-4-one and 5-hydroxy-2-methylchrom-4-one were also inhibitory but with less activity. The new inhibitors differed from the well-known phenolic inhibitors such as caffeic acid in inhibition kinetics as demonstrated by the rate of disappearance of indole-3-acetic acid, the rate of formation of the oxidation products, and the transient spectral change in the enzyme.     

Microbial transformation of 17alpha-ethynyl- and 17alpha-ethylsteroids, and tyrosinase inhibitory activity of transformed products

The microbial transformation of the 17alpha-ethynyl-17beta-hydroxyandrost-4-en-3-one (1) (ethisterone) and 17alpha-ethyl-17beta-hydroxyandrost-4-en-3-one (2) by the fungi Cephalosporium aphidicola and Cunninghamella elegans were investigated. Incubation of compound 1 with C. aphidicola afforded oxidized derivative, 17alpha-ethynyl-17beta-hydroxyandrosta-1,4-dien-3-one (3), while with C. elegans afforded a new hydroxy derivative, 17alpha-ethynyl-11alpha,17beta-dihydroxyandrost-4-en-3-one (4). On the other hand, the incubation of compound 2 with the fungus C. aphidicola afforded 17alpha-ethyl-17beta-hydroxyandrosta-1,4-dien-3-one (5). Two new hydroxylated derivatives, 17alpha-ethyl-11alpha,17beta-dihydroxyandrost-4-en-3-one (6) and 17alpha-ethyl-6alpha,17beta-dihydroxy-5alpha-androstan-3-one (7) were obtained from the incubation of compound 2 with C. elegans. Compounds 1-6 exhibited tyrosinase inhibitory activity, with compound 6 being the most potent member (IC(50)=1.72 microM).     

Incorporation of 14C-Formaldehyde into Hexose Phosphate by Cell-free Extract of a Methanolutilizing Yeast,Candida sp.

The persistence and degradation of isoxathion ¹⁴C-labeled at the 5-position of the isoxazole ring were studied in three soil types under laboratory conditions. Persistence was influenced by soil type and moisture content; approx. half life at 30 ppmw dose level varied from 15 to 40 days in nonflooded models. In a flooded model isoxathion disappeared much faster. Isoxathion underwent biodegradation to a number of products with concomitant release of ¹⁴CO₂. 3-Hydroxy-5-phenylisoxazole, 5-phenyl-4-oxazolin-2-one, benzoylacetamide and benzoic acid were the unequivocally identified metabolites; oxon derivative of isoxathion, 3-methoxy-5-phenylisoxazole, 2-methyl-5-phenyl-4-isoxazolin-3-one, 2-acetyl-5-phenyl-4-isoxazolin-3-one, 2, 5-diphenylpyrazine and acetophenone were tentatively identified as the minor products. None of these major products was persistent in soils. 3-Hydroxy-5-phenylisoxazole, the initial metabolite or hydrolyzate of isoxathion, was adsorbed to soil to a much greater extent than isoxathion, which explains the rapid disappearance of its fungicidal activity in soil.     

Antiprogestational agents. The synthesis of 7-alkyl steroidal ketones with anti-implantational and antidecidual activity

A series of 7α- and 7β- alkyl derivatives of steroidal 4-en- and 5-en-3-ones were prepared by 1,6-conjugate addition of organocopper reagents to various steroidal 4,6-dien-3-ones of the androstane, estrane and gonane series. Biological study of these and related compounds revealed that 17β-hydroxy-7α-methyl-5-androsten-3-one (2), 17β-hydroxy-7α-methyl-5-estren-3-one acetate and 17β-hydroxy-7α-methyl-4-estren-3-one acetate had significant anti-implantational and antidecidual activities. The contragestative effects were associated with the latter antihormonal properties, and not with the androgenicity of these compounds.     

Chromones from the tubers of Eranthis cilicica and their antioxidant activity

Chemical studies on the constituents of Eranthis cilicica led to isolation of ten chromone derivatives, two of which were previously known. Comprehensive spectroscopic analysis, including extensive 1D and 2D NMR data, and the results of enzymatic hydrolysis allowed the chemical structures of the compounds to be assigned as 8,11-dihydro-5-hydroxy-2,9-dihydroxymethyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, 5,7-dihydroxy-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-2-methyl-4H-1-benzopyran-4-one, 5,7-dihydroxy-2-hydroxymethyl-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-4H-1-benzopyran-4-one, 7-[(β-d-glucopyranosyl)oxy]-5-hydroxy-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-2-methyl-4H-1-benzopyran-4-one, 7-[(β-d-glucopyranosyl)oxy]-5-hydroxy-2-hydroxymethyl-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-4H-1-benzopyran-4-one, 9-[(O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl)oxy]methyl-8,11-dihydro-5,9-dihydroxy-2-methyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, 8,11-dihydro-5,9-dihydroxy-9-hydroxymethyl-2-methyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, and 7-[(O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl)oxy]methyl-4-hydroxy-5H-furo[3,2-g][1]benzopyran-5-one, respectively. The isolated compounds were evaluated for their antioxidant activity.     

Metabolism of progesterone by chorionic cells of the early sheep conceptus invitro

Progesterone-4-¹⁴C was extensively metabolized during incubation with dispersed trophoblast prepared from chorionic membranes of the 21-day sheep conceptus. Of the metabolites formed, 17,20α-dihydroxypregn-4-en-3-one, 20α-hydroxypregn-4-en-3-one, 20(β-hydroxypregn-4-en-3-one, 5α-pregnane-3α,17,20α-triol, 5β-pregnane-3ga, 17,20α-triol, 5β-pregnane-3g,20α-diol, 3β-hydroxy-5α-pregnan-20-one, 3α-hydroxy-5β-pregnan-20-one, 20β-hydroxy-5β-pregnan-3-one, 5α-pregnane-3,20-dione and 5β-pregnane-3,20-dione were identified. These findings indicate that the sheep conceptus acquires extensive steroid metabolizing capability very early in pregnancy.     

Stereospecific reduction of progesterone by Pisum sativum

[4 -¹⁴C]-Progesterone was applied to the leaves of growing pea plants, Pisum sativum. After 3 weeks, about 50% of the administered steroid was reduced, about 20% being reduced to 5α-pregnane-3α,20β-diol as the major metabolite. The radioactivities of 5α-pregnane-3α,20α-diol and 5α-pregnane-3α,20β-diol after 3 weeks were more than twice those after one week. The following radioactive metabolises were also isolated: 5α-pregnane-3,20-dione; 20α-hydroxy-4- pregnen-3-one; 20β-hydroxy-4-pregnen-3-one; 3α-hydroxy-5α-pregnan-20-one; 3α-hydroxy-5β-pregnan-20-one; 3β-hydroxy- 5α-pregnan-20-one; 20β-hydroxy-5α-pregnan-3-one; 5α-pregnane-3β,20β-diol; and 5β-pregnane-3α,20β-diol. The radioactivities of the 5α-pregnane derivatives were considerably higher than those of the corresponding 5β-pregnane derivatives.     

The in vivo metabolites of [14C] progesterone in bovine muscle and adipose tissue

Muscle and adipose tissue were obtained from steers and dairy cows following subcutaneous administration of [¹⁴C] progesterone. Following extraction, purification and separation by column, thin layer and gas-liquid chromatography, various radioactive residues from these tissues were identified by their Chromatographic mobility, crystallization to constant specific activity and mass spectra. Progesterone constituted 54% of free radioactivity extracted from muscle and 69 and 73% of radioactivity in the free and conjugated portions of extracts, respectively, from fat. Metabolites identified were: 5α-pregnane-3,20-dione, 9%, 0%, 0%, 20β-hydroxy-4-pregnen-3-one, 8%, 11%, 3%; 3α-hydroxy-5β-pregnan-20-one, 13%, 2%, 2%; 3α-hydroxy-5α-pregnan-20-one, 3%, 3%, 6%; 20α-hydroxy-5α-pregnan-3-one, 0%, 2%, 3%; of radioactivity in muscle (free) and fat (free and conjugated fractions), respectively. Tentatively identified in fat extracts by chromatographic mobility were: 20α-hydroxy-4-pregnen-3-one, 1%, 1% and 3β-hydroxy-5β-pregnan-20-one, 0%, 2% of radioactivity in free and conjugated fractions, respectively. The average concentration of steroid in these animals due solely to treatment, calculated from the specific activity of the [¹⁴C] progesterone administered, was 3.4 and 18.1 ng/g in muscle and subcutaneous fat, respectively.     

生姜中6个姜辣素类成分的抗菌活性研究

为了探究生姜化学成分的抗菌活性及初步构效关系,采用色谱法从生姜中分离得到6个姜辣素类化合物,采用波谱法对这6个成分进行鉴定,分别为5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-4-decen-3-one(1)、5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-4-dodecen-3-one(2)、5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-4-tetradecane-3-one(3)、[6]-姜酚(4)、[8]-姜酚(5)和[10]-姜酚(6)。采用抗菌纸片扩散法测定6个化合物对15株病原菌株的抗菌活性。结果表明化合物1和4抗菌活性最好,而6对所有菌株均无活性。初步构效关系分析表明:烯醇型化合物对革兰氏阳性菌的抗菌活性优于姜酚型化合物;而姜酚型化合物对革兰氏阴性菌的抗菌活性优于烯醇型化合物。此外,姜辣素类成分脂肪链的长度增加,可能导致抗菌活性降低。     

Effects of various radicinin analogs on pulse amplitude and arterial blood pressure

The action of some radicinin analogues on the pulse amplitude in urethane anesthetized rats has been studied. The compounds used are:2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (I); 2,3-dihydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (II) 7,8-dihydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (III) 2,3,7,8-tetrahydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione(IV); 2,3,7,8,4',8'-hexahydro-2,7-dimethyl-4H,5H-pyrano[4, 3-b]pyran-4,5-dione (V); 3-crotonyl-4-hydroxy-6-methyl-2H-pyran-2-one (VI); 3-hexanoyl-4-hydroxy-6-methyl-2H-pyran-2-one (VII); 3-hexanoyl-5,6-dihydro-4-hydroxy-6-methyl-2H-pyran-2-one (VIII). A clear increase in the pulse has been seen with the compounds (II), (V) and (VII) especially at the lowest doses, while a decrease in the pulse is caused by the compounds (I) and (VIII). The studied substances have no effects on systolic blood pressure in normotensive unanesthetized rats.     

Iron(III) and aluminum(III) complexes with hydroxypyrone ligands aimed to design kojic acid derivatives with new perspectives

With the aim to design new chelators for the clinical treatment of different diseases involving the trivalent metal ions Fe(III) and Al(III), we present the equilibria of kojic acid and its derivative 6-[5-hydroxy-2-hydroxymethyl-pyran-4-one]-5-hydroxy-2-hydroxymethyl-pyran-4-one with these two metal ions. Potentiometric and spectrophotometric techniques for iron, and potentiometry and ¹H NMR for aluminum were used, supported by X-ray, electrospray ionization-mass spectrometry (ESI-MS), calorimetry and quantum chemical calculations. In this work, evidence is given on the formation of MeL, MeL₂, and MeL₃ complexes of both metal ions with kojic acid, confirmed by the X-ray structure of the FeL₃ complex, and of variously protonated Me₂L₂ and MeL₂ complexes of 6-[5-hydroxy-2-hydroxymethyl-pyran-4-one]-5-hydroxy-2-hydroxymethyl-pyran-4-one. The extremely good pFe value for this second ligand gives confidence to, and opens perspectives for, the search of new kojic acid derivatives.     

Homoisoflavonoids from the inter-bulb surfaces of Scilla nervosa subsp. rigidifolia

Eight homoisoflavonoids, two of which are new: 3-(4′-methoxybenzyl)-5,6,7-trimethoxychroman-4-one (1); 3-(4′-methoxybenzyl)-5,7-dimethoxychroman-4-one (2); 3-(4′-methoxybenzyl)-7-hydroxy-5,6-dimethoxychroman-4-one (3); 3-(4′-methoxybenzyl)-6-hydroxy-5,7-dimethoxychroman-4-one (4); 3-(3′-hydroxy-4′-methoxybenzyl)-5,7-dihydroxy-6-methoxychroman-4-one (5); 3-(3′-hydroxy-4′-methoxybenzyl)-5,7-dihydroxychroman-4-one (6); 3-(4′-hydroxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one (7) and 3-(4′-hydroxybenzylidene)-5,7-dihydroxychroman-4-one (8), were isolated from the yellow Inter-bulb deposits from Scilla nervosa. The structures of these compounds were elucidated and characterized by 1D- and 2D-NMR and mass spectrometry. The structures of the known compounds were compared to those ones in literature.     

Conversion of 20alpha-hydroxy-4-pregnen-3-one to 20alpha-hydroxy-5alpha-pregnan-3-one and 5alpha-pregnane-3alpha, 20alpha-diol by rat anterior pituitary

³H-20α-hydroxy-4-pregnen-3-one was incubated with anterior pituitaries from proestrous rats. The $\text{in vitro}$ metabolic products, identified by reverse isotopic dilution and purification to constant specific activity, were 20α-hydroxy-5α-pregnan-3-one (23.0%) and 5α-pregnane-3α,20α-diol (11.4%). These are qualitatively the same metabolites which result from $\text{in vitro}$ incubation of 20α-hydroxy-4-pregnen-3-one with medial basal hypothalamus. 68.8% of the recovered radioactivity remained as 20α-hydroxy-4-pregnen-3-one. These three compounds accounted for all of the recovered radioactivity.