Ein neues Kawainolderivat aus Piper sanctum

A New Kavainol Derivative from Piper Sanctum From the wooden underground parts of Piper sanctum (5S,6S)-(+)-5-hydroxy-4,6-dimethoxy-6-trans-styryl-5,6-dihydro-2H-pyran-2-one ( 1 ) was isolated with 0.2 percent yield. Structure and absolute configuration of this compound have been assigned by comparison of its acetate with a previously described product 2 obtained from the same plant¹⁾.     

Synthese und Eigenschaften des 3-Hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]chinazolin-2-carbonitrils

Synthesis and Properties of 3-Hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]quinazoline-2-carbonitrile Anthranilic acid reacts with 2-chloro-5-cyano-4-hydroxypyrid-6-one (3) in glacial acetic acid to yield 3-hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]quinazoline-2-carbonitrile (4) . When the reaction is carried out in DMF under Ullmann conditions, 2-(dimethylamino)-5-cyano-4-hydroxypyrid-6-one (5) forms as a by-product. The methylation of 3 with diazomethane affords 2-chloro-5-cyano-2-methoxy-N-methylpyrid-6-one (9) and 2-chloro-5-cynao-4,6-dimethoxypyridine (10) . Under similar conditions compound 4 undergoes an esterifying ring cleavage to furnish methyl 2-(5-cyano-4,6-dimethoxypyrid-2-ylamino)benzoate (7) .     

(Hydroxyphenyl)ethanones from dehydroacetic acid (author's transl)]

(Hydroxyphenyl)ethanones from Dehydroacetic Acid Dehydroacetic acid ( 4 ) reacts with N,N-dimethylformamide dimethylacetal to yield 4-hydroxy-6-methyl-3-[3-(dimethylamino)acryloyl]-2H-pyran-2-one ( 5 ). Unsuccessful attempts to produce the pyranopyrandiones 1 and 2 or the 2-[(dimethylamino)vinyl]-6-methyl-4-pyrone ( 3 ) by heating 5 with dilute sulfuric acid are reported. The reaction yields 1-(2,4-dihydroxyphenyl)ethan-1-one ( 9 ). Similarly 1-(2-methylamino-4-hydroxyphenyl)ethan-1-one ( 8 ) was obtained from the enamine 7 , and the pyran-2,4-dione 12 from the coumarin derivative 10 .     

Synthesis of novel triazolyl pyranochromen-2(1<Emphasis Type="Italic">H</Emphasis>)-ones and their antibacterial activity evaluation

A series of thirty-three novel triazolyl pyranochromen-2(1H)-one derivatives have been synthesized via Cu (I) catalysed Huisgen 1,3-dipolar cycloaddition reaction. All of the synthesized compounds have been fully characterized from their spectral data and evaluated for antibacterial activity against both gram-positive and gram-negative bacteria. The activity results revealed that amongst all the compounds screened, six compounds, i.e. 2-[4-(((7-ethyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]acetic acid (41), 10-[(1-(1,3-dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-3-ethyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (44), 3-ethyl-4,8,8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (46), 2-[4-(((7-hexyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]acetic acid (52), 10-[(1-(1,3-dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-3-hexyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (55) and 3-hexyl-4,8,8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (57), exhibited moderate activity against all the strains studied with zone of inhibition between 10 and 16 mm and MIC values in the range of 75–170 µg/mL as compared to the standard used. The information obtained from structure–activity relationship can be used to design and develop the next generation of compounds with higher antibacterial efficacy.     

Two new 2-(2-phenylethyl)chromones from Chinese eaglewood

Two new 2-(2-phenylethyl)chromones, (5S ^*,6R ^*,7S ^*)-5,6,7-trihydroxy-2-(3-hydroxy-4-methoxyphenethyl)-5,6,7,8-tetrahydro-4H-chromen-4-one (1) and (5S ^*,6R ^*,7R ^*)-5,6,7-trihydroxy-2-(3-hydroxy-4-methoxyphenethyl)-5,6,7,8-tetrahydro-4H-chromen-4-one (2), were isolated from the Chinese eaglewood of Aquilaria sinensis (Lour.) Gilg. Their structures were established by detailed MS and NMR spectroscopic analysis, as well as comparison with the literature data.     

Enantioselective synthesis of (R)- and (S)-2-methyl-[3,3,2-2H3] alanines

The synthesis of optically pure (R)- and (S)-2-methyl-[3,3,3-²H₃] alanines of biological interest is described. The stereochemistry of the reaction of the lithio derivative of (R)-(©)-2,5-dimethoxy-3-benzyl-3-methyl-3, 6-dihydropyrazine with alkyl and deuterated alkyl iodides is discussed. The configuration of the newly formed center of chirality in (R)- and (S)-2-methyl-[3,3,3-²H₃] alanines is derived from ¹ H NMR.     

Geraniinic acid derivative from the leaves of Phyllanthus reticulatus

Chemical constituents as well as cytotoxic and insecticidal activity of the crude methanol extract from the leaves of Phyllanthus reticulatus Poir. (Euphorbiaceae) were investigated. (5R*,6R*)-4,6-Dimethoxycarbonyl-5-[2′,3′,4′-trihydroxy-6′-(methoxycarbonyl) phenyl]-5,6-dihydro-2H-pyran-2-one (1) along with 3,4,3′-tri-O-methylellagic acid, and methyl gallate were isolated from the dichloromethane extract. Determination of their structures was based on spectroscopic analysis. Compound 1 possessed a very weak insecticidal activity against Spodoptera frugiperda (Sf9) with an IC₅₀ value of 27.27?μg/mL.     

The Biotransformation of 8-Chloro-6-phenyl-4H-s-triazolo[4, 3-a][1,4] benzodiazepine (D-40TA), a New Central Depressant,in Man,Dog and Rat

1. Metabolic studies of 8-chloro-6-phenyl-4H-^s-triazolo [4,3-a] [1,4] benzodiazepine (D—40TA) in man, dog and rat led to identification of the following metabolites: six hydroxylation products; 8-chloro-2,4-dihydro-6-phenyl-1H-s-triazolo[4,3-a] [1,4]benzodiazepin-1-one (I), 8-chloro-6-(4-hydroxyphenyl)-4H-s -triazolo[4,3-a][1,4]benzodiazepine (II), 8-chloro-6- (3-hydroxyphenyl)-4H-s-triazolo[4,3-a] [1,4] benzodiazepine (III), 8-chloro-4-hydroxy-6-phenyl-4H-s- triazolo[4,3-a][1,4]benzodiazepine (IV), 8-chloro-2,4-dihydro-6- (4-hydroxy-phenyl)-1H-s-triazolo[4,3-a] [1,4] benzodiazepin-1-one (V) and 8-chloro-2,4-dihydro-6-(3-hydroxyphenyl)- 1H-s- triazolo[4,3-a][1,4]benzodiazepin-1-one (VI); five ring-opened metabolites; 5-chloro-2-(4H-1,2,4-triazol-4-yl) -benzophenone (VII), 5-chloro-2- (2,3-dihydro-3-oxo- 4H -1,2,4- triazol-4-yl)benzophenone (VIII), 5-chloro-2- (2,3-dihydro-3-oxo-4H - 1,2,4-triazol-4-yl)-2-hydroxybenzophenone (IX), 5-chloro-2- (2,3-dihydro-3-oxo-4H-1,2,4-triazol-4-yl)-4'-hydroxybenzophenone (X) and 5-chloro-2-(3,5-dioxo-2,3,4,5-tetrahydro-1H-1,2,4-triazol-4-yl) benzophenone(XI).

2. In man, metabolites I, IV, VII and VIII are present as the free form in the urine, and I, II, IV and VIII are present as conjugates. In the dog, all the metabolites are present. The rat transforms the compound mainly to metabolites I, II, IV and V. None of the ring-opened metabolites are observed in the rat.     

Enantioselective synthesis of tri-deuterated (–)-geosmin to be used as internal standard in quantitation assays

For the accurate and sensitive quantitation of the off-flavor compound geosmin, particularly in complex matrices, a stable isotopologue as internal standard is highly advantageous. In this work, we present a versatile synthetic strategy leading from (4aR)-1,4a-dimethyl-4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one to tri-deuterated (–)-geosmin ((4S,4aS,8aR)-4,8a-dimethyl(3,3,4-²H₃)octahydronaphthalen-4a(2H)-ol). The starting material was readily accessible from inexpensive 2-methylcyclohexan-1-one using previously published procedures.     

A novel kainate receptor ligand [H]-(2S,4R)-4-methylglutamate: Pharmacological characterization in rabbit brain membranes

Since kainate evokes large non-desensitizing currents at α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, kainate is of limited use in discriminating between AMPA and kainate receptors. Following recent reports that (2S,4R)-4-methylglutamate is a kainate receptor-selective agonist, we have radiolabelled and subsequently characterized the binding of [³H]-(2S,4R)-4-methylglutamate to rabbit whole-brain membranes. [³H]-(2S,4R)-4-methylglutamate binding was rapid, reversible and labelled two sites (KD1 = 3.67 ± 0.50 nM/B_max1 = 0.54 ± 0.03 pmol/mg protein and K_D2 = 281.66 ± 12.33 nM/ B_max2 = 1.77 ± 0.09 pmol/mg protein). [³H]-(2S,4R)-4-methylglutamate binding was displaced by several non-NMDA receptor ligands: domoate > kainate -quisqualate -glutamate > 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) (S)-AMPA = (S)-5-fluorowillardiine > NMDA. Neither the metabotropic glutamate receptor agonists (1S,3R)-ACPD or -AP4, together with the -glutamate uptake inhibitor -trans-2,4-PDC, influenced binding when tested at 100 μM. We conclude that [³H]-(2S,4R)-4-methylglutamate is a useful radioligand for labelling kainate receptors. It possesses high selectivity, and possesses a pharmacology similar to that for rat cloned low-affinity (Glu5 and 6) kainate receptor subunits.     

Über die Reaktion von 3,5-Diacetyl-2,6-dimethyl-4H-pyran-4-on mit Natriumalkanolaten

On the Reaction of 3,5-Diacetyl-2,6-dimethyl-4H-pyran-4-one with Sodium Alkoxides The reaction of 3,5-diacetyl-2,6-dimethyl-4H-pyran-4-one (10) with sodium methoxide or ethoxide leads to the formation of the 1-acetyl-2-hydroxy-4-methyl-6-alkoxybenzenes 11a and 11b .     

Two new acetylated flavan glycosides from rhizomes of the fern Abacopteris penangiana

Two new acetylated flavan glycosides (2S,4R)-4,5,7-trihydroxy-4′-methoxy-6,8-dimethylflavan-5-O-β-D-6-acetylglucopyranoside-7-O-β-D-glucopyranoside (1) and (2S,4R)-5,7-dihydroxy-4,4′-dimethoxy-6,8-dimethylflavan-5-O-β-D-6-acetylglucopyranoside-7-O-β-D-glucopyranoside (2) were isolated from the rhizomes of Abacopteris penangiana. Their structures were elucidated on the basis of spectroscopic methods including IR, HR-ESI-MS, 1D and 2D NMR, and chemical evidences.     

A new chromone and a new aliphatic ester isolated from Daldinia eschscholtzii

Abstract

A new chromone and a new aliphatic ester were isolated from the EtOAc extract of myceliums of Daldinia eschscholtzii. Their structures were elucidated as (R)-5-hydroxy-8-methoxy-2-methylchroman-4-one (1) and (E)-6-(non-3-en-1-yl) -2H-pyran-2-one (2) by interpretation of the spectroscopic evidence.     

Accumulation of 5-Ethyl-2′-deoxyuridine and its 5,6-Dihydro Prodrugs in Murine Lung and its Potential Clinical Application

The accumulation of 5-ethyl-2′-deoxyuridine (EDU), (–)-trans-(5S, 6S)-5-bromo-5-ethyl-6-methoxy-5,6-dihydro-2′-deoxyuridine [(5S, 6S)-BMEDU], (+)-trans-(5R, 6R)-5-bromo-5-ethyl-6-methoxy-5,6-dihydro-2′-deoxyuridine [(5R, 6R)-BMEDU], (+)-trans-(5.R, 6R)-5-bromo-5-ethyl-6-ethoxy-5, 6-dihydro-2′-deoxyuridine (BEEDU), (+)-trans-(5R, 6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-5′-O-valeryl-2′- deoxyuridine (VBEEDU) and (+)-trans-(5R, 6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-3′-5′-di-O-valeryl-2′-deoxyuridine (DVBEEDU) in lung and other tissues was investigated in male Balb-C mice following intravenous injection of the corresponding 4-¹⁴C-labelled compounds. EDU showed a rapid distribution into liver and lung immediately after injection, and the overall levels of radioactivity in blood, liver and lung were similar. The distribution of radioactivity in lung after injection of [4-¹⁴C](5S, 6S)-BMEDU and [4–14C](5R, 6R)-BMEDU were substantially different from one another and also from that of [4-¹⁴C]EDU. The radioactivity level present in lung samples after injection of both [4-¹⁴C](5S, 6S)-BMEDU and [4-¹⁴C](5R, 6R)-BMEDU was substantially higher than that in blood samples. Radioactivity levels present in lung samples taken at 18 min after injection of [4-¹⁴C]BEEDU were significantly higher (P < 0·05) than those for liver and blood samples. Although the radioactivity present in lung samples after injection of [4-¹⁴C]VBEEDU was significantly higher (P < 0·05) than those of liver and blood samples, [4-¹⁴C]VBEEDU did not provide a higher radioactivity level in lung samples than did [4-¹⁴C]BEEDU. The level of radioactivity in lung samples following injection of [4-¹⁴C]DVBEEDU was also higher than that of blood samples. EDU undergoes glycosidic bond cleavage to form EU in lung following intravenous injection into Balb-C mice. The concentrations of EDU and 5-ethyluracil (EU) following intravenous injection of EDU, and its prodrugs BEEDU and VBEEDU, were quantitated in lung and blood samples. In contrast to lung samples, EU was not detected in blood samples at 120 min post injection of EDU. The concentrations of both EDU and EU in lung tissues after injection of BEEDU and VBEEDU were substantially higher than those in blood samples.     

Olefinierungsreaktionen des 5H-Cyclopenta(cd)phenalen-5-on

Olefination Reactions of 5H-Cyclopenta[cd]phenalen-5-one We describe olefination reactions of 5H-cyclopenta[cd]phenalen-5-one (1) with diphenyl ketene, phenyl cyano ketene, tert.-butyl cyano ketene, and methyl cyano ketene to yield compounds 2–6 . Also, further the synthesis of 2-[bis(methylthio)methylene]-2H-naphtho[1,8-bc]thiophene (6) is described.     

New α-pyrone and phthalide from the Xylariaceae fungus

A new α-pyrone xylaripyrone A (1) and a new phthalide xylariphthalide A (2) were isolated from the Xylariaceae fungus (no. 63-19-7-3), along with four related known phthalides (3–6): 4-[(acetyloxy)methyl]-7-methoxy-6-methyl-1(3H)-isobenzofuranone (3), convolvulol (4), 7-methoxy-4,6-dimethyl-3H-isobenzofuran-1-one (5), and convolvulanic acid B (6). Their structures were determined on the basis of IR, MS, and NMR spectroscopic analyses.     

Beiträge zur Chemie des Pyridazinsystems, 34. Mitt.: Synthese neuer Diaza-Analoga des Acridons,Xanthons und Thioxanthons aus 3,4-disubstituierten Pyridazinen

Pyridazine Chemistry XXXIV^{1, 2)}: Synthesis of Novel Diaza Analogues of Acridone, Xanthone and Thioxanthone from 3,4-Disubstituted Pyridazines. Reactions of 3-chloropyridazine-4-carbonitrile 5 with arylamines, phenol or thiophenol, followed by PPA promoted cyclisation, provide access to the new tricyclic systems pyridazinol 3,4-b|quinolin-5(10H)one,5H-|1|benzopyrano|2,3-c|pyridazin-5-one and 5H-|1|benzothiopyrano|2,3-c|pyridazin-5-one.     

Synthesis and Antiviral Activity of 5-Ethyl-5-halo-6-alkoxy-(or Azido)-5,6-dihydro-2′-deoxyuridine Diastereomers as Potential Prodrugs to 5-Ethyl-2′-deoxyuridine

A group of 5-ethyl-5-halo-6-alkoxy (or azido)-5,6-dihydro-2′-deoxyuridines, which differ in configuration at the C-5 and C-6 positions, were synthesized by the regiospecific addition of XR (X = I, Br, Cl; R = alkoxyl, azido) to the 5,6-olefinic bond of 5-ethyl-2′-deoxyuridine (EDU). In vitro antiviral (HSV-1, HSV-2, HCMV, VZV) activities were determined. Structure-activity studies showed that the C-5 halogeno (I, Br, Cl) and C-6 alkoxy (OMe, OEt) or azido, substituents were determinants of antiviral activity where the (5R,6R)- 5 and (5S,6S)- 6 diastereomers of 5-ethyl-5-iodo-6-methoxy-5,6-dihydro-2′-deoxyuridine exhibited greater potency against HSV-1, HSV-2, and HCMV than the related 5-chloro-6-ethoxy and 5-bromo (or chloro)-6-azido diastereomers. The most potent antiviral agents, (+)-trans-(5R,6R)- 5 and (?)-trans-(5S,6S)- 6 diastereomers of 5-ethyl-5-iodo-6-methoxy-5,6-dihydro-2′-deoxyuridine were approximately 2-to-8 fold more potent than the reference drug EDU against HSV-1 and HSV-2.     

Two new neolignan glucosides from Arctii Fructus

Two new neolignan glucosides named (7S, 8R)-4,7,9,9′-tetrahydroxy-3,3′-dimethoxyl-7′-oxo-8-4′-oxyneolignan-4-O-β-d-glucopyranoside (1) and (7′S, 8′R, 8S)-4,4′,9′-trihydroxy-3,3′-dimethoxy-7′,9-epoxylignan-7-oxo-4-O-β-d-glucopyranosyl-4′-O-β-d-glucopyranoside (2), together with two small molecular peptides named 3-benzyl-6-(1-hydroxyethyl)-2,5-piperazinedione (3) and 3-benzyl-2,5-piperazinedione (4), were isolated from the extract of Arctii Fructus. Their structures and absolute configurations were elucidated by various spectroscopic methods (IR, HR-ESI-MS, 1D and 2D NMR, and CD).     

A Search for New 5-HT1A/5-HT2A Receptor Ligands. In Vitro and in vivo Studies of 1-[ω-(4-Aryl-1-piperazinyl)alkyl]indolin-2(1H)-ones

A series of 1-[ω-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-one derivatives 2–14 was synthesized in order to obtain ligands with a dual 5-HT_1A/5-HT_2A activity. The majority of those compounds ( 2–5, 7, 10–13 ) exhibited a high 5-HT_1A (K_i = 2 – 44 nM) and/or 5-HT_2A affinity (K_i = 51 and 39 for 5 and 7 , respectively). Induction of lower lip retraction (LLR) and behavioral syndrome and inhibition of these efects evoked by 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) were used for determination the agonistic and antagonistic activity, respectively, at 5-HT_1A receptors. The 5-HT_2A antagonistic activity was assessed by the blocking effect on the head twitches induced by (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in mice. Two of the tested compounds, 1-{3-[4-(3-chlorophenyl)-1-piperazinyl]propyl}-6-fluoroindolin-2(1H)-one ( 5 ) and 1-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl}indolin-2(1H)-one ( 7 ), demonstrated a high 5-HT_1A/5-HT_2A affinity and an in vivo antagonistic activity towards both receptor subtypes.