Harvesting canthinones: identification of the optimal seasonal point of harvest of Zanthoxylum chiloperone leaves as a source of 5-methoxycanthin-6-one

This article is focused on the seasonal variation in the contents of 5-methoxycanthin-6-one from the leaves of Zanthoxylum chiloperone (Rutaceae). Based on the pharmacological interest presented by 5-methoxycanthin-6-one, its seasonal variation in Z. chiloperone leaves was analysed in order to determine the best time for harvesting, optimising the 5-methoxycanthin-6-one content. The seasonal dynamics of canthinone alkaloids can be the key to improve the isolation from natural sustainable sources, such as leaves. Complementarily, this study describes the phytochemistry of leaf from this Ruraceae species.     

Notiz über die Synthese von Iso-, Noriso- und Desäthyl-tuboflavin

Treatment of 4,5 -dihydrocanthin-6-one (V) (prepared from synthetic canthinone (IV)) with ethyl or methyl magnesium iodide and methanolic hydrochloric acid yielded the ethyl or methyl compounds VI and IX. Oxidation of the latter compounds with selenium dioxide in dimethylformamide gave rise to the Pleiocarpa alkaloids isotuboflavine (II) and norisotuboflavine (III) in low yields. Deethyltuboflavine (VIII) was isolated as a byproduct from further oxidation of norisotuboflavine.     

Pharmacokinetic and bioavailability study of 5-hydroxy-4-methoxycanthin-6-one,a typical canthinone alkaloid,in rats using ultra-high performance liquid chromatography/electrospray ionization tandem mass spectrometry

5-methoxycanthin-6-one, a major canthinone alkaloid isolated from Picrasma quassioides, exhibited significant pharmacological activities. In this study, a rapid and sensitive LC–MS/MS method was established and validated for the determination of 5-hydroxy-4-methoxycanthin-6-one in rat plasma. Small quantities (20 μL) of plasma sample were used for sample preparation. 5-Hydroxy-4-methoxycanthin-6-one and an internal standard (IS, caffeine) were separated using an ACQUITY HSS T3 column (50 × 2.1 mm, 1.7 μm; Waters, Milford, MA, USA). The mobile phase was composed of 0.1% formic acid in water and acetonitrile. Precursor-to-product ion transitions were m/z 267.0 → 168.2 and m/z 195.0 → 138.1 for quantitative monitoring of 5-hydroxy-4-methoxycanthin-6-one and IS, respectively. The assay was linear over the concentration range of 0.5–500 ng/mL (r > 0.99) with the lower limit of quantification 0.5 ng/mL. Other parameters, including intra- and inter-day precision and accuracy, carryover, stability, extraction recovery, matrix effect, and dilution effect, were within acceptable limits. The validated method was successfully applied to pharmacokinetic study in rats after intravenous (5 mg/kg) and oral (10, 25, 50 mg/kg) administration of 5-hydroxy-4-methoxycanthin-6-one. The result indicated that 5-hydroxy-4-methoxycanthin-6-one was quickly absorbed into the blood and reached the highest concentration at ~33.0–42.0 min, with moderate elimination half-life (0.85–2.11 h) and low bioavailability (16.62–24.42%) after oral administration. The study provided valuable information that can be used as a reference for studying other canthinone alkaloids.     

Total synthesis of deoxymannojirimycin and d-mannolactam via carbonylation of 5-vinyloxazolidin-2-ones

The stereoselective synthesis of piperidine alkaloids deoxymannojirimycin and d-mannolactam from d-serine has been achieved. The key step involves palladium-catalysed decarboxylative carbonylation of a serine-derived 5-vinyloxazolidin-2-one to give 6-(tert-butyldimethylsilyloxymethyl)-3,6-dihydro-1H-pyridin-2-one which was subsequently converted into the title compounds.     

Transformed steroids. 123. Synthesis of 5α(H)- and 5α(OH)-6-ketosteroids with an additional 17α,20ξ-dihydroxytetrahydropyran ring E

The paper is devoted to the synthesis of 3,17α,20-trihydroxy-16β,23-epoxy-21,24-dinor-5αH-cholan-6-one and 3,5α,17α,20-tetrahydroxy-16β,23-epoxy-21,24-dinorcholan-6-one and derivatives of them. It has been shown that the reduction of 3,17α-dihydroxy-16β,23-epoxy-21,24-dinorchol-5-en-20-one with sodium tetrahydroborate and with diborane takes place stereospecifically with different spatial directivities: in the products of diborane reduction, ring E exists in the boat form, as has been shown by¹H and¹³C NMR methods. The trans linkage of rings A/B in the modified steroids has been confirmed by their circular dichroism spectra.     

Direct quantum chemical calculation of rotatory strengths of methylpyrrolidones : Model compounds containing a peptide group

CNDO/S method is used to compute the rotatory strengths of L-5-methylpyrrolid-2-one and S-3-methylpyrrolid-2-one, cyclic compounds containing a peptide group. The observed circular dichroism (CD) bands in the regions of 185 and 220 nm corresponded to π → π^* and n → π^* transitions, respectively. The computed rotatory strengths indicate that nonplanarity of pyrrolidone ring makes a substantial contribution to the CD of compounds under consideration. The comparison of computed and experimental rotatory strengths suggests that both compounds have a nonplanar ring conformation.     

Solvent-controlled dehydration and diastereoselective formation of indenone-fused thiazolo[3,2-a]pyridines via a one-pot four-component reaction

A solvent-controlled four-component reaction has been described for the preparation of either hydroxy-tetrahydro-thiaza-cyclopenta[c]fluoren-6-one or dihydro-thiaza-cyclopenta[c]fluoren-6-one from nitroketene dithioacetals, cysteamine hydrochloride, 1,3-indandione and aromatic aldehydes starting materials by changing solvent systems. These reactions proceed under catalyst-free conditions affording a range of two types of skeletally distinct thiazolo[3,2-a]pyridines-based heterocycles. Hydroxy-tetrahydro-thiaza-cyclopenta[c]fluoren-6-one was obtained in H₂O/EtOH (3:1, v/v) in high yield and diastereoselectivity but in contrast dihydro-thiaza-cyclopenta[c]fluoren-6-one was synthesised in EtOH in moderate to good yields and in the longer reaction time. The structural diversities have been confirmed spectroscopically, by IR ¹H and ¹³C NMR, and EI-MS spectra, which agree with the proposed structures.     

Synthesis and stereochemistry of (−)-(10s)-6,10-dimethyl-6-aza-δ1,9-octahydroquinoline

Enantiomericalfy pure (–)-(10S)-6,10-dimethyl-6-am-^1,9-octahydroquinoline, which has been obtained from optically pure (3S)-1,3-dimethyl-3-(2-cyanoethyl)piperid-4-one, is a chiral intermediate for the preparation of novel biologically active compounds and an analog of piperidine and decahydroquinoline alkaloids. The chiroptical properties of the synthesized 6-azaoctahydroquinoline are examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1379–1383, October, 1992.     

Alkylations of tricyclo[5.2.1.0]deca-4,8-dien-3-one by a cuprate reaction

Alkylation at C₆ of tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one (R=H) was achieved by treatment of 6-bromotricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one with lithium dimethylcuprate and subsequently with an appropriate electrophile. The best results were obtained in THF as the solvent. A wide range of alkyl halides, bromo ketones and esters, and acetyl chloride resulted in C₆-tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-ones in moderate to good yields. This alkylation reaction proceeds via a C₆-carbanionic Cu intermediate, which is likely stabilized by the enone olefinic bond. 6-Bromo-endo-tricyclo[5.2.1.0^2,6]dec-8-en-3-one, which lacks this double bond, behaves differently. Treatment with lithium dimethylcuprate leads to dehydrobromination to give tricyclo[5.2.1.0^2,6]deca-2(6),8-dien-3-one in high yield.     

Trigonoines A and B, two novel alkaloids from the leaves of Trigonostemon lii

Two novel alkaloids, trigonoine A containing a 2,8-diazabicyclo[3.3.1]nonane ring system and trigonoine B formed by a combination of a 2,3-dihydroquinolin-4-one and 3H-pyrrolo[2,3-c]quinoline rearranged from β-carboline skeleton were isolated from the leaves of Trigonostemon lii. Their structures were elucidated by 1D and 2D NMR spectroscopic methods.     

Structure of the alkaloids of Aerva lanata

By the NOE method using¹³C NMR and UV spectra we have confirmed the structures of four new alkaloids isolated previously: 10-hydroxycanthin-6-one (ervine), 10-methoxycanthine-6-one (methylervine), 10-β-D-glucopyranosyloxycanthin-6-one (ervoside), and 6-methoxy-β-carbolin-l-ylpropionic acid (ervolanine). All-Union Scientific-Research Institute of Drugs Scientific-Production Association, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 821–824, November–December, 1991.     

2-Phenyl-4-quinolinone Alkaloids from Casimiroa edulis Llave et Lex (Rutaceae)

 Three new 4-quinolinone alkaloids (5,6-dimethoxy-2-(3-methoxyphenyl)-1H-quinolin-4-one, 5,6-dimethoxy-2-(3,4-dimethoxyphenyl)-1H-quinolin-4-one, 5,6-dimethoxy-2-(2,5,6-trimethoxyphenyl)-1H-quinolin-4-one) were isolated from the leaves of Casimiroa edulis Llave et Lex (Rutaceae) cultivated in Egypt. Their structures were determined by UV/Vis, IR, ¹H and ¹³C NMR, and EI mass spectroscopy. The alkaloids were also detected in the kernels of the seeds.     

2-Phenyl-4-quinolinone Alkaloids from Casimiroa edulis Llave et Lex (Rutaceae)

Summary.  Three new 4-quinolinone alkaloids (5,6-dimethoxy-2-(3-methoxyphenyl)-1H-quinolin-4-one, 5,6-dimethoxy-2-(3,4-dimethoxyphenyl)-1H-quinolin-4-one, 5,6-dimethoxy-2-(2,5,6-trimethoxyphenyl)-1H-quinolin-4-one) were isolated from the leaves of Casimiroa edulis Llave et Lex (Rutaceae) cultivated in Egypt. Their structures were determined by UV/Vis, IR, ¹H and ¹³C NMR, and EI mass spectroscopy. The alkaloids were also detected in the kernels of the seeds. Received May 28, 2001. Accepted (revised) July 24, 2001     

Antifungal Activity of New Diterpenoid Alkaloids Isolated by Different Chromatographic Methods from Delphinium peregrinum L. var. eriocarpum Boiss

This paper aimed to investigate the potential antifungal influences of new alkaloids from Delphinium peregrinum L. var. eriocarpum Boiss. New Diterpenoid alkaloids Delcarpum (1), Hydrodavisine (4) and known alkaloids Peregrine (2), Delphitisine (3) were isolated by different chromatographic methods from the aerial parts of D. Peregrinum eriocarpum Boiss, which grows in Syria. The structures of alkaloids were proposed based on 1D NMR spectroscopy ¹H-NMR, ¹³C-NMR, DEPT-135, DEPT-90, 2D NMR spectroscopy DQF-COSY, HMQC, EI-Ms mass spectrum, and IR spectroscopic measurements. The antifungal activity of the isolated alkaloids was evaluated against different dermatophyte fungal isolates compared with fluconazole. In the case of Peregrine (2) the minimum inhibitory concentrations(MICs) recorded 128–256, 32–64, and 32 for Epidermophyton floccosum, Microsporum canis, and Trichophyton rubrum, respectively, compared to 32–64, 16, and 32 μg/mL in the case of fluconazole, respectively. The MICs recorded on application of the four alkaloids mixture were 64, 32, and 16 in the case of E. floccosum, M. canis, and T. rubrum, respectively, which were significantly lower than that measured for each of the individual alkaloid and were compatible for fluconazole. In conclusion, MICs of the tested alkaloids showed a variable potential effect on the investigated fungal isolates. Peregrine (2) was the most effective alkaloid, however, the application of the mixture of alkaloids induced significant synergistic activity that was more pronounced than the application of individual ones.     

Effect of high-voltage electric pulses on yeast cells: factors influencing the killing efficiency

The decisive factors determining the killing efficiency of single rectangular electric pulses of 4–28 kV cm⁻¹ amplitude and 1–300 μs duration in Saccharomyces cerevisiae S6/1 are pulse amplitude and duration, cell size and growth phase, post-pulse temperature and medium conductivity. In S. cerevisiae, the minimum pulse duration ensuring substantial killing is about 10 μs, the minimum amplitude being about 2 kV cm⁻¹. The critical pulse-induced transmembrane breakthrough voltage is 0.75 V. A pulse-induced increase in membrane permeability for small species such as inorganic ions suffices to cause cell death. A preset killing rate can be achieved by varying pulse amplitude inversely to pulse duration. Comparison of killing data on S. cerevisiae S6/1 with those on the smaller-celled Kluyveramyces lactis showed the killing pulse amplitude to be roughly proportional to cell size except for low pulse amplitudes, at which smaller cells are much more killing-prone. In exponential S. cerevisiae cells increased pulse amplitude caused a sharp increase in killing while in stationary cells this effect was much lower and occurred only at pulse amplitude above 15–20 kV cm⁻¹. Elevated post-pulse temperature lowered the killing rate whereas lowered temperature promoted it, probably by affecting the pore resealing. Lowering medium conductivity from 66 to 46 μS m⁻¹ by suspension washing reduced the killing rate by 6–20%. Reproducible killing or electroporation therefore requires standardized cell concentration, and number of cell washings.     

Stereoselective synthesis of cyclohexa-2,4-dien-1-ones and cyclohex-2-en-1-ones from phenols

A convenient synthetic method for the synthesis of substituted cyclohex-2-en-1-ones by the direct alkylation of phenols has been developed. Furthermore, enantiomerically enriched 2,6-dimethyl-6-(3-methylbut-2-enyl)-cyclohexa-2,4-dienone was prepared by the deprotonation of 2,6-dimethylphenol with a sparteine–lithium complex followed by alkylation with 1-chloro-3-methylbut-2-ene. 2,6-Dimethyl-6-(3-methyl-but-2-enyl)-cyclohex-2-enone was prepared from the corresponding cyclohexa-2,4-dien-1-one by selective hydrogenation of the 4,5-double bond. The method was extended to 2-methyl-naphthalen-1-ol and 1-methyl-naphthalen-2-ol resulting in 2-(R)-methyl-2-(3-methylbut-2-enyl)-2H-naphthalen-1-one and 1-(S)-methyl-1-(3-methylbut-2-enyl)-1H-naphthalen-2-one, respectively.     

Norditerpenoid alkaloids from <Emphasis Type="Italic">Aconitum septentrionale K</Emphasis>.

Two new alkaloids, Septonine (C₃₅H₄₄N₂O₉) and Septontrionine (C₂₅H₃₉NO₆) were isolated from the roots of Aconitum septentrionale K. According to the ¹H and ¹³C NMR, IR, and mass spectra, Septonin and Septontrionin were assigned the structures of 20-ethyl-7-hydroxy-1α,14α,16β-trimethoxy-6-oxo-17(7→8)abeoaconitan-4-ylmethyl 2-(2,5-dioxopyrrolidin-l-yl)benzoate and 20-ethyl-7-hydroxy-1α,14α,16β-trimethoxy-4-methoxymethyl-17(7→8)abeoaconitan-6-one, respectively.     

Study on the biosynthesis of the notoamides: Pinacol-type rearrangement of the isoprenyl unit in deoxybrevianamide E and 6-hydroxydeoxybrevianamide E

Two reverse-prenylated indole alkaloids, deoxybrevianamide E and 6-hydroxydeoxybrevianamide E, are proposed as biosynthetic precursors for advanced metabolites isolated from the marine-derived Aspergillus sp. In order to uncover the role of the alkaloids in the biosynthetic pathway, the feeding experiments of the [¹³C]₂-[¹⁵N]-labeled deoxybrevianamide E and 6-hydroxydeoxybrevianamide E were performed to afford the metabolites, which were produced by oxidation and successive pinacol-type rearrangement of the isoprenyl units.     

Rhodium catalyzed hydroacylation of ethylene with 4-pentenals. reactions of 4-hexenal-1-d

A catalyst derived from 2,4-pentanedionatobis(ethylene)rhodium(I), I, promoted the addition of 4-pentenal to ethylene. The reaction was accompanied by the formation of double bond migration products derived from the 4-pentenal reactant and from the 6-hepten-3-one primary product. Compound I accomplished the addition of 4-hexenal to ethylene to afford high yields of 6-octen-3-one. The fate of the aldehyde hydrogen in this transformation has been determined in experiments employing 4-hexenal-1-d as reactant. Treatment of 4-hexenal-1-d with I in CHCl₃ and CDCl₃ afforded 6-octen-3-one possessing >50% d_o molecules while the isotopic composition of recovered unexpended 4-hexenal remained >96% d₁. 6-Octen-3-one products with isotopic compositions of >66% d_o were afforded when ethylene was introduced to reaction mixtures. The location of deuterium in 6-octen-3-one, derived from treatment of 4-hexenal-1-d with I in the absence of added C₂H₄, was determined to be distributed at C-1 and C-2 and at the CC bond by analysis of the ¹H and ²H NMR spectra. Unexpended ethylene was recovered and was found to contain a substantial amount of deuterium. Mechanistic implications of these results are discussed.     

Iron(III) catalyzed direct C–H functionalization at the C-3 position of chromone for the synthesis of fused chromeno-quinoline scaffolds

This communication describes an iron-catalyzed route for the synthesis of 6-substituted chromeno[3,2-c]quinolin-7-one. The method developed does not require any pre-functionalization to execute the pivotal coupling reaction at the C-3 position of flavones. The final step involves the consecutive application of imine formation, C_sp²-C_sp² coupling and oxidation reaction, with aromatic aldehydes and 2-(2-aminophenyl)-4H-chromen-4-one as the reactants. Presence of electron donating/withdrawing groups was well tolerated in the aldehydes and the method developed could also be extended to other substituted 2-(2-aminophenyl)-4H-chromen-4-one’s. This is the first report of synthesis of 6-substituted chromeno[3,2-c]quinolin-7-one’s via direct functionalization of the C-3 site of flavones.