Indolalkaloids of Pleiocarpa talbotii Wernham. 145. Alkaloids

Besides talbotine ( 1 ) three new indole alkaloids, talpinine ( 2 ), talcarpine ( 3 ) and 16-epi-affinine ( 4 ) were isolated from the stem bark of Pleiocarpa talbotii Wernham. The structure of 2 was deduced by chemical degradation and by analyses of the spectra of the alkaloid and its derivatives. One of these derivatives is identical with talcarpine ( 3 ). The structures 2 and 3 are similar to that of macroline ( 14 ), a splitting product of the bisindole alkaloid villalstonine from Alstonia species. 16-epi-Affinine ( 4 ) was chemically correlated with the known alkaloid vobasine ( 19 ). Talpinine ( 2 ) and 16-epi-affinine ( 4 ) were also isolated from the root bark of Pleiocarpa talbotii.     

Alkaloids of Arundo donax L. 13. The structure of a new dimeric indole alkaloid,arundanine

The structure of a new dimeric indole alkaloid, named arundanine, isolated from the roots of Arundo donax L. (Poaceae), was elucidated. Arundanine was identified as 3-(N,N-dimethylaminoethyl)-4-[3-(N,N-dimethylaminoethyl)indole-1-yl]-5-hydroxyindole on the basis of spectroscopic data and the transformation into the known alkaloid, arundamine.     

Elucidation of the structure of quindolinone,a minor alkaloid of cryptolepis sanguinolenta: Submilligram 1H-13c and 1H-15N heteronuclear shift correlation experiments using micro inverse-detection

Elucidation of minor natural product structures has been significantly augmented by inverse-detection; further improvement has been afforded by the development of micro inverse-detection probes. We report here the elucidation of the structure of a new alkaloid, quindolinone (5H, 10H-indolo[3,2-b]quinolin-11-one), from the West African plant Cryptolepis sanguinolenta. All nmr data for this minor, preparative hplc-isolated alkaloid, including ¹H-¹⁵N one? bond heteronuclear shift correlation (HMQC) data, were recorded on an 800 μg sample of the alkaloid dissolved in 140 μl of 100% d₆-DMSO using a 400 MHz spectrometer.     

Alkaloid production by callous tissue cultures of Cereus peruvianus (Cactaceae)

The morphologically undifferentiated cells of nonregenerant callous tissue of Cereus peruvianus cultured in the original medium and in medium supplemented with tyrosine were used as an alkaloid source. Comparison of alkaloid production by C. peruvianus plants and by callous tissues indicated that alkaloid levels were almost twice as high in callous tissues as in shoots of C. peruvianus plants. The ratio of alkaloid concentration between mature plant and morphologically und ifferentiated cells of callous tissue was 1∶1.7. A relationship between culture medium containing tyrosine and alkaloid production was also observed in the callous tissues of C. peruvianus. Since increased alkaloid production may be induced by additional factors such as tyrosine, increasing levels of tyrosine or other conditions of the culture medium may be considered factors for inducing higher alkaloid production by C. peruvianus callous tissues.     

Kopsine and Danuphylline Alkaloids from Kopsia. Biomimetic Partial Synthesis of Danuphylline B

Two new indole alkaloids, 12‐methoxykopsine ( 6 ) and danuphylline B ( 7 ), were obtained from the leaf extract of the Malayan Kopsia species, K. arborea, and their structures established by spectroscopic analysis. An electrochemically‐mediated partial synthesis of the ring‐opened alkaloid, danuphylline B from the hexacyclic alkaloid, methyl N(1)‐de(methoxycarbonyl)chanofruticosinate was carried out.     

Über die Konstitution zweier neuartiger «dimerer» Indolalkaloide Pycnanthin und Pleiomutinin 132. Mitteilung über Alkaloide

The «dimeric» indole alkaloid (+)-pycnanthine ( 2 ) has been isolated, along with (+)-pleiocarpamine, (+)-quebrachamine, (+)-macusine B and an unknown alkaloid D from Pleiocarpa pycnantha (K. SCHUM .) STAPF , var. pycnantha M. PICHON. An investigation of its chemical and spectroscopic properties has led to the determination of structure 2 for this base. Its 6′,7′-dihydro derivative has been shown to be identical with the alkaloid pleiomutinine, previously isolated from Pleiocarpa mutica BENTH .     

Verbascenin,ein macrocyclisches Spermin-Alkaloid aus verbascum 184. Mitteilung über organische Naturstoffe

Verbascenine, a Macrocyclic Spermine Alkaloid Isolated from Verbascum The new spermine alkaloid verbascenine ( 1 ) has been isolated from extracts of the aerial parts of Verbascum phoeniceum L. and V nigrum L. The structure of the alkaloid was elucidated by chemical degradation and by a study of the spectral properties of the alkaloid and its derivatives. Compared to the 13-membered alter native 7 the 17-membered structure 1 is preferred on the basis of mass spectral arguments.     

Synthesis of the alkaloid thalactamine and a new synthesis for the alkaloid N-methyl-6,7-dimethoxy-1(2H)isoquinolone

The alkaloid thalactamine (N-methyl-5,6,7-trimethoxy-1(2H)isoquinolone) was synthesised in two steps from 4,5,6-trimethoxyhomophthalic acid (1a). Heating la with DMF/POCI₃ at 100° furnished thalactamine-4-earhoxylic acid which was easily decarboxylated to give the alkaloid thalactamine. By the same two steps, the alkaloid N-methyl-6,7-dimethoxy-1(2H)-isoquinolone is obtained from 4,5-dimethoxyhomophthalic acid. Synthesis for la from 2-bromogallic acid trimethyl ether was modified to give excellent yield. 5,6,7-Trimethoxy and 6,7-dimethoxyisocoumarin-4-carboxylic acid esters were synthesised from the homophthalic acids 1a and b by interacting them with DMF/phosphoryl chloride at 0°, to give corresponding 4-(N,N-dimethylaminoformylidene)isochroman-1,3-dione derivatives Vla and b and treating their alcoholic solutions with dry hydrogen chloride gas. The isocoumarins were converted into N-methyl-1(2H)isoquinolonesby treating them with aqueous methylamine. The isochromandione Vla slowly changed into 3-chloro-4-formyl-5,6,7-trimethoxyisocoumarin during the working up of the reaction.     

On the constitution of the macralstonidines

The alkaloid macralstonidine, which was originally isolated from Alstonia macrophylla WALL . by T. M. SHARP in 1934, has the molecular formula C₄₁H₄₈O₃N₄. The hydrolysis of this dimeric alkaloid yielded the macroline derivative 5 , N_(a)-methyl-sarpagine ( 6 ) and formaldehyde. Partial acid cleavage under deuterating conditions gave 5 -d₉, 6 -d₃ and decadeuterated macralstonidine. On the basis of spectral data, particularly an analysis of the mass spectra of macralstonidine and its decadeutero derivative, structure 2 has been elucidated for this alkaloid.     

Natural (−)‐Vasicine as a Novel Source of Optically Pure 1‐Benzylpyrrolidin‐3‐ol

A facile and scalable methodology for the preparation of optically active (3S)‐1‐benzylpyrrolidin‐3‐ol ( 3 ), an important drug precursor, is reported. Starting from the naturally occurring alkaloid (?)‐vasicine ( 1 ), a major alkaloid of the plant Adhatoda vasica, 3 was obtained in 84% overall yield (Scheme 3).     

Three New Alkaloids from Hippophae rhamnoides Linn. subsp. sinensis Rousi

Two novel organic amide alkaloids, 4‐[(E)‐p‐coumaroylamino]butan‐1‐ol ( 1 ) and 4‐[(Z)‐p‐coumaroylamino]butan‐1‐ol ( 2 ), together with a rare pyridoindole alkaloid, hippophamide ( 3 ), were isolated from the seed residue of Hippophae rhamnoides Linn . subsp. sinensis Rousi . Their structures were determined by spectroscopic means. The results show that compounds 1 and 2 are (E/Z)‐isomers, compound 3 , a pyridoindole alkaloid concerted with γ‐lactam ring.     

Hypepontine,a new quaternary alkaloid with antimicrobial properties

Abstract

New isoquinoline alkaloid hypepontine (1) together with a five known compounds, were identified in Hypecoum ponticum Velen, the partial synonym of Hypecoum procumbens L. The structure of the new substance was elucidated based on spectroscopic evidence. The tertiary and quaternary alkaloid mixtures as well as the isolated alkaloids were evaluated for their antibacterial and antifungal activity. The result revealed that the crude alkaloid mixture containing quaternary isoquinoline alkaloids showed potent antifungal and antibacterial activity.     

Isolation and elucidation of the structure of homocryptolepinone

The structure of a new indolobenzazepine alkaloid, homocryptolepinone, isolated from extracts of the roots of the indigenous Ghanaian medicinal plant Cryptolepis sanguinolenta, is reported. The structure was determined using mass spectrometric, one-dimensional nOe difference nmr, and inverse-detected two-dimensional nmr experiments which included HMQC, IDR-(Inverted Direct Response)-HMQC-TOCSY, and HMBC experiments. The structure of homocryptolepinone is significant in that it may provide insight into the biogenesis of the benzpyrrolizinobenzazepine portion of the structure of the complex spiro nona-cyclic alkaloid cryptospirolepine previously isolated in these laboratories from C. sanguinolenta, and which has no precedent in alkaloid chemistry.     

Total Synthesis of (−)-(2R)-Dihydromyricoidine

An asymmetric synthesis of the spermidine alkaloid (?)-(2R)-dihydromyricoidine ( 5 ) was performed by employing two ring-enlargement reactions. The chiral center was introduced by a diastereoselective Michael addition of perhydropyridazine ( 7 ) to the α,β-unsaturated ester 6 . The (Z)-C?C bond was obtained by a selective Wittig reaction. The synthetic compound 5 was found to have a negative value for the specific rotation. This is in contrast to that of the natural product reported in the literature. Therefore, as an outcome of this synthesis, the absolute configuration of the natural alkaloid should be inverted to be as shown in structure V .     

Enantioseparation of nornicotine in tobacco by ultraperformance convergence chromatography with tandem mass spectrometry

Nornicotine, an alkaloid constituent of tobacco, is a precursor to the carcinogen N‐nitrosonornicotine that is produced during the curing and processing of tobacco. Accumulating evidence reveals that nornicotine enantiomers have different neurochemical and behavioral effects. In the present study, an accurate and rapid method was developed for the enantioseparation of (R )‐(+)‐nornicotine and (S )‐(−)‐nornicotine enantiomers in tobacco by ultra‐performance convergence chromatography with tandem mass spectrometry. Chromatographic conditions were investigated to achieve the optimal resolution of two enantiomers. Results indicated that (R )‐(+)‐nornicotine and (S )‐(−)‐nornicotine could be separated within 5 min when ammonium hydroxide was added into the cosolvent, and the best resolution (R _s = 4.76) was achieved on a immobilized cellulose tris‐(3,5‐dichlorophenylcarbamate) chiral stationary phase. The proposed method was validated and was finally applied to analyze the compositions of (R )‐(+)‐nornicotine and (S )‐(−)‐nornicotine in three typical types of tobaccos (flue‐cured, burley, and oriental). It was found that, enantiomer fraction of nornicotine (the proportion of (S )‐(−)‐nornicotine in the nornicotine pool) in burley tobacco samples was relatively high and constant compared with flue‐cured and oriental tobaccos. The effective and rapid enantioseparation of nornicotine may help the understanding of alkaloid metabolites in different tobacco varieties and may also benefit pharmacological studies of alkaloid enantiomers.     

The chemistry of 2h-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 17 Synthesis of 2-alkyl-4-quinolone alkaloids via a one-step reaction of N-methylisatoic anhydride with methyl ketone enolates

Lithium enolates derived from aliphatic methyl ketones react with N-methylisatoic anhydride (5) at ?78° to give 2-alkyl-4-quinolone alkaloids 7 in a single step. The method was used to synthesize both double bond isomers of 1-methyl-2-(8-tridecenyl-4(1H)-quinolinone (8) thereby showing that the alkaloid evocarpine possesses the Z-olefin stereochemistry 8a. Reduction of 8a provided the alkaloid dihydroevocarpine (16). Compound 16 was also directly prepared from the reaction of 5 with the lithium enolate of 2-pentadecanone.     

Macrocarpamin,ein neues Bisindolalkaloid aus Alstonia macrophylla WALL. 167. Mittelung über organische Naturstoffe

Macrocarpamine, a new bisindole alkaloid from Alstonia macrophylla WALL . A new bisindole alkaloid give the name (?)-macrocarpamine ( 3 ) was isolated from the bark of Alstonia macrophylla WALL . Under pyrolytic conditions 3 is cleaved into the two known bases (+)-pleiocarpamine ( 2 ) and (?)-anhydro macrosalhin-methin ( 5 ) (Scheme 1). The structure of 3 (including relative configuration) was deduced on the basis of chemical evidence and from its UV.-, IR.-, NMR.- and mass spectroscopic data.     

Mass‐spectrometry‐directed analysis and purification of pyrrolizidine alkaloid cis/trans isomers in Gynura japonica

Pyrrolizidine alkaloids are highly hepatotoxic natural chemicals that produce irreversible chronic and acute hepatotoxic effects on human beings. Purification of large amounts of pyrrolizidine alkaloids is necessary for toxicity studies. In this study, an efficient method for targeted analysis and purification of pyrrolizidine alkaloid cis/trans isomers from herbal materials was developed for the first time. Targeted analysis of the hepatotoxic pyrrolizidine alkaloids was performed by liquid chromatography with tandem mass spectrometry (precursor ion scan and daughter ion scan), and the purification of pyrrolizidine alkaloids was achieved with a mass‐directed auto purification system. The extraction and preparative liquid chromatography conditions were optimized. The developed method was applied to analysis of Gynura japonica (Thunb.) Juel., a herbal medicine traditionally used for detumescence and relieving pain but is potentially hepatotoxic as it contains pyrrolizidine alkaloids. Twelve pyrrolizidine alkaloids (six cis/trans isomer pairs) were identified with reference compounds or characterized by liquid chromatography with tandem mass spectrometry, and five individual pyrrolizidine alkaloids, including (E)‐seneciphylline, seneciphylline, integerrimine, senecionine, and seneciphyllinine, were prepared from G. japonica roots with high efficiency. The results of this work provide a new technique for the preparation of large amounts of pyrrolizidine alkaloid reference substances, which will also benefit toxicological studies of pyrrolizidine alkaloids and treatments for pyrrolizidine alkaloid‐induced toxicity.     

Synthesis of Oncinotin-11-one,a Macrocyclic Polyamine Alkaloid from Oncinotis tenuiloba

This paper presents a short synthesis of oncinotin-11-one ( 11 ), a minor alkaloid of Oncinotis tenuiloba (Apocynaceae). Based on a disconnection approach, the spermidine portion of the key intermediate 6 was constructed consecutively by simple N-alkylations starting from ethyl piperidine-2-carboxylate ( 1 ). Treatment of 6 with in situ lithiated 2-[(10-bromodecyl)oxy]tetrahydropyran resulted in the formation of the keto moiety under simultanous deprotection of the lactam N-atom to give the amino ketone 7 in 71% yield. Cleavage of the tetrahydro-2H-pyran-2-yl(Thp) portion and Jones oxidation of the resulting alcohol 8 gave the amino acid 9 which was cyclized. Final N-debenzylation of 10 provided the natural alkaloid 11 . Only two protective groups were needed in this synthesis. The reaction of N-alkyl-lactams with organometallic reagents is discussed.     

Concerning the alkaloid eripine from Hunteria umbellata

Eripine, a new indole alkaloid, was isolated from the leaves of Hunteria umbellata. The spectral data of the alkaloid, of eripinic acid and the O-acetyl and 19, 20-dihydro derivatives of the alkaloid led to the structure II. Heating of II gave a mixture (ratio 3,5:1) of the known alkaloid erinine (I) and its stereoisomer, isoerinine (VII), which is not found in nature. The same mixture was obtained on heating either erinine or isoerinine.