Alkaloids from Bulbocodium vernum L. Content material of Liliaceae-Wurmbaeoidaea

From whole plants of Bulbocodium vernum L. the flavone luteoline (I) and the alkaloids colchicine (II), N-formyl-N-deacetylcolchicine (III), 3-demethylcolchicine (V), (+)-bulbocodine (IX) and (?)-kreysigine (XI) were isolated in crystals. The presence of 2-demethylcolchicine (IV), ß- (VII) and γ-lumicolchicine (VIII), demecolcine (VI) and five not identified alkaloids was demonstrated by thin-layer chromatography. On the basis of ultraviolet, infrared and mass spectra, PMR.-analysis (Overhauser effect), and circular dichroism, the (6a-R, 8a-S)homo-proaporphine structure IX, with one methoxy group at C-2, has been assigned to (+)-bulbocodine. The (6a-R)-structure (XI) was deduced for (?)-kreysigine by comparing its optical rotation and circular dichroism which the values of (?)-multifloramine (X), the structure of which is known.     

Studies on the Alkaloids of Formosan Lauraceous Plants XVIII Alkaloids of Neolitsea Buisanensis Yamamoto Et Kamikoti and Neolitsea Aurata (Hay.) Koidz

Two alkaloids, laurolitsine (V) and litsericine (VII), were isolated from the woods of Neolitsea buisanersis. Six alkaloids were isolated from the woods of Neolitsea aurata and five of them were laurolitsine (V), litsericine (VII), N–methyllitsericine (VIII), (+)–anonaine (IX), and (–)-roemerine (X) (Table I).     

Dibenzo[b,f]oxepin‐10(11H)‐one and dibenzo[b,f]thiepin‐10(11H)‐one as useful synthons in the synthesis of various dibenzo[e,h]azulenes

The present review focuses on dibenzo[b,f]oxepin‐10(11H)‐one ( I , X = O) and dibenzo[b,f]thiepin‐10(11H)‐one ( I , X = S) as common synthons in the efficient synthesis of various dibenzoxepino[4,5‐ and dibenzothiepino[4,5]‐fused five‐membered heterocycles: [2,3] fused thiophene ( II ), [3,4] fused thiophene ( III ), furan ( IV ), pyrrole ( V ), imidazole ( VI ), pyrazole ( VII ), oxazole ( VIII ), and thiazole ( IX ). The potential of I to be converted into reactive intermediates that readily undergo heteroaromatic annulation reactions by cyclocondensation with proper binucleophiles allows formation of a range of enumerated functionalized dibenzo[e,h]azulene [4] structures ( II , III , IV , V , VI , VII , VIII , IX ). Dibenzo[e,h]azulenes as heterotetracyclic scaffold can be exploited in further modifications to obtain compounds with altered physicochemical and biological profile. J. Heterocyclic Chem., (2012).     

Contribution à la phytochimie du genre Gentiana,VI. Etude des xanthones dans les feuilles de Gentiana bavarica L.

Ten tetraoxygenated xanthones (1-hydroxy-3, 7, 8-trimethoxyxanthone I; 1, 7-dihydroxy-3, 8-dimethoxyxanthone II; 1, 7, 8-trihydroxy-3-methoxyxanthone III; 1, 3, 7, 8-tetrahydroxyxanthone IV; 3, 7, 8-trimethoxyxanthone-1-O-primeveroside V; 7-hydroxy-3, 8-dimethoxyxanthone-1-O-primeveroside VI; 1, 8-dihydroxy-3-methoxyxanthone-7-O-acetylrutinoside VII; 7, 8-dihydroxy-3-methoxyxanthone-1-O-primeveroside VIII; 3, 7, 8-trihydroxyxanthone-1-O-primeveroside IX; 3, 7, 8-trihydroxyxanthone-1-O-glucoside X) have been isolated from leaves of Gentiana bavarica L . by means of column chromatography on polyamid. Among these xanthones, VI, VII, VIII and IX were not encountered before in nature.     

Über in 6-Stellung basisch substituierte Morphanthridine. 8. Mitteilung über siebengliedrige Heterocyclen

Morphanthridines III with a basic substituent in position 6, which show neuroleptic activity, have been synthesised as follows: Chlorination of the lactams I with POCl₃ gave the iminochlorides II, which were converted by bases to the amidines III. The 11-oxo-morphanthridines VI and VII were synthesised using the same procedure, 2-(1-methylpiperazine-4-carbonyl)-2′-amino-benzophenone (XI) was obtained directly from the 6-chloro-11-oxo-morphanthridine (V) or by extended heating of VI with N-methylpiperazine. Reduction of the 11-oxo-compounds VI and VII with NaBH₄ gave the 11-hydroxy-compounds IX and X. 3-(2-aminophenyl)-phtalide (VIII) resulted from the acid hydrolysis of IX.     

Synthese des (R)-trans-11-Hydroxy-8-dodecensäure-lactons (Recieifeiolid)

Synthesis of Recifeiolide The synthesis of the mould metabolite recifeiolide (VIII), a 12-membered ring lactone, is described. 1,3-Butandiol was resolved with (?)-camphanic acid via (R)-1-iodo-3-butanol (II) into (R)-3-hydroxybutyl triphenyl phosphonium iodide (III). Wittig condensation of the phosphorane derived from III with methyl 8-oxo-octanoate (V) led to the methyl trans-11-hydroxy-8-dodecenoate (VI). The corresponding hydroxy acid VII was transformed into the S-(2-pyridyl) carbothioate which cyclizes under the influence of silver ion to the lactone VIII. With (?)-(R)-1,3-butandiol (I) as starting material the naturally occurring (+)-(R)-recifeiolide (VIII) is produced in 70% yield from VII.     

Studies on the syntheses of analgesics. Part XXXII. An alternative synthesis of 1,2,3,4,5,6-Hexahydro-8-hydroxy-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazoeine [Studies on the syntheses of heterocyclic compounds. Part CDLXXX]

Bischler-Napieralski reaction of the amides (VIII and IX), derived from the 3-methyl-3-pentenylamine (III) with the phenylacetic acid derivatives (V ～ VII), gave the 5,6-dihydropyridines (XII and XIII), which were reduced, followed by N-benzylation, to afford the 1,2,5,6-tetrahydropyridines (XIX ～ XXI). Grewe-type cyclization of these compounds gave 3-benzyl-3-benzazocine (II), which was already converted into pentazocine (Ic). Moreover, the 1,2,5,6-tetrahydropyridines (XIX ～ XXI) were also obtained from the 2-benzylidene-1,2,5,6-tetrahydropyridine (XVII ～ XVIII) from the N-benzylamine (IV) of III via the amides (X and XI).     

2-(Trimethylsilyl)äthylester als Carboxylschutzgruppe; Anwendung bei der Synthese des (−)-(S)-Curvularins

2-(Trimethylsilyl)ethyl Esters as Carboxyl Protecting Group; Application in the Synthesis of (?)-(S)-Curvularin The mould metabolite curvularin (VIII) has been synthesized with the help of a new carboxyl protecting group that can be removed selectively with fluoride ions. 2-(Trimethylsilyl)ethyl 7-hydroxy-octanoate (III) was acylated with 3,5-dibenzyloxy-phenacetyl chloride (IV) to form V with two different ester groups. Tetrabutyl-ammonium fluoride in tetrahydrofuran cleaved the 2-(trimethylsilyl)ethyl ester in V selectively to form the carboxylate anion of VI together with ethylene and trimethylsilyl fluoride. Curvularin dibenzyl ether (VII) was formed by intramolecular acylation of VI. Removal of the benzyl ether groups in VII by hydrogenolysis led to (±)-curvularin (VIII). The naturally occurring (?)-enantiomer was formed when (+)-(S)-III served as starting material.     

Studies on the syntheses of heteroeyelie compounds. Part DVI . Synthesis of oxynilidine and nitidine

A benzyne type reaction of 1-bromo-3,4-dimethoxybenzene (V) with 3,4-dihydro-6,7-methylenedioxy-I(2H)naphthalenone (VI) gave the tetralone derivative VII, which was converted into the amine IX via the oxime VIII. A Mannich reaction of IX afforded the benzo[c]phen-anthridine II which was then transformed into oxynitidine (I) and nitidine (IV).     

Thermische Umwandlung von Phenyl-penta-2,4-dienyläthern in 4-[Penta-2,4-dienyl]-phenole als Beispiel für [5,5]-sigmatropische Umlagerungen. Vorläufige Mitteilung

The reaction between phenol and trans penta-2,4-dienyl chloride gave trans penta-2,4-dienyl Phenyl ether (I), whereas with a mixture of sorbyl chloride and 1-methylpenta-2,4-dienyl chloride, pure trans, trans hexa-2,4-dienyl phenyl ether (IV) and trans 1-methylpenta-2,4-dienyl phenyl ether (V) were obtained. The ether I gave, on heating in dilute solution at 185°, 4-(penta-2,4-dienyl)-phenol (III) as the main product, and also some 2-(2-vinylallyl)-phenol (II). The ether IV provided, on heating at 165°, in addition to the ortho CLAISEN rearrangement product VI, mainly a mixture consisting of 94% 4-(1-methylpenta-2,4-dienyl)-phenol (VIII) and only 6% 4-(hexa-2,4-dineyl)-phenol(IX). The latter product (IX) was the only para isomer produced on heating ether V, but in addition 22% of the ortho rearrangement product VII was formed. The migrations I → III, IV → VIII, and V → IX, proceeding through a ten membered transition state, are the first [5,5] sigmatropic rearrangements described.     

Metabolism of terniary compounds. V. Decomposition of diincarbonic acids and hydrocarbons in vivo

10,12-Heneicosadiynoic acid (I), 5,7-hexadecadiynoic acid (IV), and 10,12-docosadiynedioic acid (VI) were fed to rats. As metabolites 4,6-undecadiynedioic acid (II), 5,7-dodecadiynedioic acid (V), and 4,6-decadiynedioic acid (VII) respectively were isolated from the urine. 10,12-Heptadecadiynoic acid (III) also yielded metabolite II. Furthermore 9,11-eicosadiyne (X) and for comparison purposes eicosane (XI), hexadecanedioic acid (VIII), and docosanedioic acid (IX) were fed. X and XI were incorporated into depot fat and liver lipids to a cetain degree. The diynes I, II, IV, and X are new compounds.     

Metallionen und H2O2. IV. Über Struktur und Aktivität der den H2O2-Zerfall katalysierenden Cu2+-Komplexe. II. Einfluss der Zahl der freien Koordinationsstellen

The Cu²⁺ chelates of the bidentate ligands 2,2′-bipyridine (I; [2]), N, N′-diglycyl-1,5-diaminopentane (VI), ethylenediamine (II; [2]), glycine (V) and pyrophosphate (III; [2]) are found–parallel to the spectrochemical series–to be more active in catalysis of H₂O₂ decomposition than the chelates of the terdentate ligands–antiparallel to the spectrochemical series–iminodiacetic acid (IX), glycylglycine (VIII), 2, 2′-diaminodiethylamine (VII) and 2, 2′, 2″-terpyridine (IV; [2]), the activity decreasing in the given series. If all four coordination positions of Cu²⁺ are engaged (e.g. complex with N, N′-di-(2-aminoethyl)-ethylenediamine (X)) the complex is inactive. The catalytic activity of the Cu²⁺-chelates is parallelled by the tendency to form ternary peroxo complexes.     

Studies on the Alkaloids of Lotus Receptacle

From lotus receptacle (seed pod of Nelumbo nucifera Gaertn., four alkaloids, nuciferine (I), N-nornuciferine (VIII), oxoushinsunine (IX) and N-norarmepavine (X) were isolated. Identification of these bases were carried out by their spectral data and direct comparison with authentic samples. It is interesting that oxoushinsunine (IX), a cytotoxic alkaloid shows tumor inhibitory activity against nasopharynx carcinoma reported recently by D. Warthen et al¹³⁾. The biscoclaurine (IV and V) and quaternary water soluble base (VI) only occures in the embryo. Comparison their alkaloids distribution in each part of Formosan lotus was listed in the Table 1.     

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.     

Synthesis of new heterocyclic ring systems. Reaction of indolines and hexahydrocarbazole with α,β-unsaturated acids

Reactions of indoline (I), 2-methylindoline (II) and hexahydrocarbazole (III) with α,β-unsaturated acids in the presence of polyphosphoric acid have been investigated. Reaction of 1 with acrylic acid afforded two compounds which were identified as 1,2,4,5-tetrahydro-6H-pyrrolo-[3,2,1-ij] quinolin-6-one (IV) and 2,3,5,6,9,10-hcxahydro-1H-cyclopenta[f lpyrrolo [3,2,1-ij|-quinoline-1,8-dione (VII). The reaction oi 1 with crotonic acid gave compounds V and VIII, analogous-to IV and VII. The reaction of II with acrylic acid yielded two compounds VI and IX, whereas with crotonic acid, only X was isolated. With 111, acrylic acid afforded 5,6,8,9,10. 11,8a,11a-octahydro-4H-pyrido[3,2,1-jk]carbazol-4-one (XI) and a compound with a heretofore unknown ring system, viz., 2,3,5,6,7,8,11,12,5a,8a-decahydro-1H-cyclopenta[h] pyrido [3,2,1-jk |earbazole-1,10-dione. The structures of these compounds were deduced on the basis of their spectral and analytical data.     

Synthese der isomeren 3, 4-Dimethyl-4-phenyl-3, 4-dihydro-carbostyrile

Cyclisation of 2-methyl-3-phenyl-but-3-en-anilide (III) with polyphosphoric acid gave cis-3, 4-dimethyl-4-phenyl-3, 4-dihydro-carbostyril (VII) in 61% yield together with a small amount of 2, 3-dimethylindenone (VIII), whereas with AlCl₃ a phenyl group was split off to give 3, 4-dimethylcarbostyril (VI). The anilide III isomerises to cis- and trans-2, 3-dimethyl-cinnam-anilide (IV resp. V) under basic conditions. The anilides IV and V gave only small yields of the dihydrocarbostyril VII with polyphosphoric acid. Chlorination of VII in position 3 using PCl₅ yielded IX which, on splitting out HCl, gave 3-methylene-4-methyl-4-phenyl-3, 4-dihydro-carbostyril (X). X was converted to trans-3, 4-dimethyl-4-phenyl-3, 4-dihydro-carbostyril (XI) by catalytic hydrogenation.     

Bioactive saponins and glycosides. XVIII. Nortriterpene and triterpene oligoglycosides from the fresh leaves of Euptelea polyandra Sieb. et Zucc. (2): Structures of eupteleasaponins VI, VI acetate, VII, VIII, IX, X, XI, and XII.

Following the elucidation of eupteleasaponins I, II, III, IV, V, and V acetate, eupteleasaponins VI, VI acetate, VII, VIII, IX, X, XI, and XII were isolated from the fresh leaves of Euptelea polyandra Sieb. et Zucc. The structures of eupteleasaponins VI-XII were determined on the basis of chemical and physicochemical evidence.     

Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. IX. Routes to substituted oxazolidin-2-ones and oxazolidine-2-thiones

4-Chlorobenzenesulfonyl isocyanate (I) reacted with 2-chloroethanol and 1-chloro-2-propanol to give, respectively, 2-chloroethyl 4-chlorobenzenesulfonyl carbamate (III) and 1-chloro-2-propyl 4-chlorobenzenesulfonyl carbamate (VI). The carbamates III and VI cyclized under the influence of pyridine to afford, respectively, 3-(4-chlorobenzenesulfonyl)oxazolidin-2-one (IV) and 3-(4-chlorobenzenesulfonyl)-5-methyloxazolidin-2-one (VII). The oxazolidin-2-ones were stable toward hydrochloric acid but hydrolyzed in 2M sodium hydroxide solution to N-(2-hydroxyethyl)-4-chlorobenzenesulfonamide (V) and N-(2-hydroxy-1-propyl)-4-chlorobenzene-sulfonamide (VIII), respectively. 4-Toluenesulfonyl isothiocyanate (II) reacted with 2-chloroethanol to give 2-chloroethyl 4-chlorobenzenesulfonyl thiocarbamate (IX), which was converted by pyridine to 3-(4-toluenesulfonyl)oxazolidine-2-thione (X).     

Studies on the Constituents of Paris Formosana Hayata Part II

Methyl palmitate (I), methyl stearate (II), stigmasterol (III), β-sitosterol (IV), (O -acyl)-β-D -glucopyranosyl-(1→3)-stigmasterol (V), (O -acyl)-β-D -glucopyranosyl-(1→3)-β-sitosterol (VI), β-D -glucopyranosyl-(1→3)-stigmasterol (VII), β-D -glucopyranosyl-(1→3)-β-sitosterol (VIII), β-D -ecdysone (IX), diosgenin-3-α-L -rhamopyranosyl-(1→2)-[α-L -arabinofuranosyl-(1→4)]-β-D -glucopyranoside (X), diosgenin-3-O -β-chacotrioside (dioscin) (XI), and diosgenin-3-O -α-L -rhamnopyranosyl-(1→4)-α-L -rhamnopyranosyl-(1→4)-[α-L -rhamnopyranosyl-(1→2)]-β-D -glucopyranoside (XII) were isolated and characterized from the stems of Paris formosana Hayata (Liliaceae).     

Synthesis of pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5-ones. Cyclization reaction of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid with acetic anhydride

Treatment of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid (X) with acetic anhydride under refluxing conditions afforded 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]-pyrimido[4,5-d]pyrimidin-5-one acetate (IX). The intermediate X was prepared from 4-chloro-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (V). The reaction of V with the sodium salt of 2-amino-3-hydroxypyridine at room temperature gave 4-(2-amino-3-pyridyloxy)-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (VI). Treatment of VI with a hot aqueous sodium hydroxide solution and subsequent acidification gave X. Involvement of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecaroboxylic acid ethyl ester (VIII) (Smiles rearrangement product) as an intermediate in the above alkaline hydrolysis reaction of VI to X was demonstrated by the isolation of VIII and its subsequent conversion into X under alkaline hydrolysis conditions. Acetylation of VIII with acetic anhydride in pyridine solution gave 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester acetate (XI), which afforded IX on fusion at 220°. This alternative synthesis of IX from XI supported the structural assignment of IX. Fusion of VI gave 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]pyrimido]4,5-d]pyrimidin-5-one (VII). The latter was also obtained when VIII was fused at 210°. Acetylation of VII with acetic anhydride afforded IX.