A new aromatic glucoside from stem bark of Illicium difengpi K.I.B. et K.I.M.

A new aromatic glucoside, namely 4-methoxyphenyl-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside (1), together with six known aromatic glucosides (2–7) were isolated from the stem bark of Illicium difengpi. The structures of these compounds were established by spectroscopic methods. The isolated aromatic glucosides were tested for anti-inflammatory activity. Compounds 1, 3 and 6 showed significant inhibitory effect on nuclear factor kappa B (NF-κB) in RAW 264.7 macrophages induced by lipopolysaccharide.     

Reassessment of Melittis melissophyllum L. subsp. melissophyllum iridoidic fraction

The analysis of the polar fraction of Melittis melissophyllum L. subsp. melissophyllum led to the identification of several iridoid glycosides: monomelittoside (1), melittoside (2), harpagide (3), acetyl-harpagide (4) and ajugoside (5). Compounds 3 and 4 are considered marker compounds for the genus and, as well as compounds 1, 2 and 5, were already evidenced in a previous study on the nominal species. It was noteworthy of the presence of allobetonicoside (6) which was never reported for this genus. The isolation of 6 is very relevant because of its allose residue on the structure. Allose has been often found in the species of the subfamily Lamioideae even if it mostly regarded flavonoids considered of chemotaxonomical relevance for some correlated genera of Lamiaceae. Same as allosyl-glycosidic flavonoids, the presence of allosyl-glycosidic iridoids may also be an additional chemosystematic evidence of botanical relationships among Lamiaceae species and genera.     

ZurFischer-Indol-Umlagerung sterisch gehinderter Systeme, 6. Mitt.: Reaktionen mit cyclischen Oxalylverbindungen, 22. Mitt.

The N,N-diphenylhydrazones1 and7 combine with oxalyl chloride yielding the corresponding 2,3-dihydropyrrole-2,3-diones (2), the indeno[1,2—b]pyrrol-2,3-dion derivative8 a and the 1-diphenylamino-4,5-tetrahydrobenz[g]indol-2,3-dione (8 b).2 can be rearranged into the pyrrolo[2,3—b]indole systems3 by thermolysis in decaline. Heating of3 a gives ethyl 1,2-diphenyl-indole-3-carboxylate5, while3 b under the same conditions is converted into the (indolyl-)glyoxylic acid derivative4. The diaza-propellanes9 are synthesized by thermolysis of8 in decaline. Oxidative hydrolysis of9 leads to the indole derivatives10, which on the other hand are made byFischer indole synthesis starting with7.     

Synthese von benzanellierten Carbacephamen 2.Mitt.

Summary The treatment of 2-(oxo-1-azetidinyl)-benzyltriphenylphosphponium salts9 and13b,c,d, ande with base leads to carbacephemes10 and14b,c,d, ande which can be reduced to the title compounds. The reaction of14 with acids does not result in 3-oxocephames by cleavage of the enolether function. Instead, the 3-alkoxyquinolines15b andc have been obtained.

     

Derivate des Methylendioxybenzols, 24. Mitt.

Zusammenfassung Es wird die Synthese des isomerenfreien 2,3-Methylendioxyallylbenzols (o-Safrols) (1 d) durch Einwirkung von Chlorbrommethan auf 2,3-Dihydroxy-allylbenzol (1 b) beschrieben.Durch Behandlung des 4-Hydroxy-3-methoxy-allylbenzols (3 a) mit Kaliumnitrosodisulfonat, Reduktion des entstehenden 3-Methoxy-5-allyl-o-benzochinons (4) mit Natriumdithionit und Methylenierung des 3-Methoxy-5-allyl-brenzcatechins (5) bildet sich Myristicin (3 b) in guter Ausbeute.

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Derivatives of methylenedioxy-benzene, XXIV: Synthesis of o-safrole and of myristicine

Preparation of 2.3-methylenedioxy-allylbenzene (o-safrole) (1 d) free of isomers by reaction of 2.3-dihydroxy-allylbenzene (1 b) with CH₂BrCl is described.Treating 4-hydroxy-3-methoxy-allylbenzene (3 a) with potassium nitrosodisulfonate gives 3-methoxy-5-allyl-o-benzoquinone (4) which ist reduced to 3-methoxy-5-allyl-pyrocatechol (5) with sodium dithionite. Methylenation of3 c gives myristicin with good yield.

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23. Mitt.:F. Dallacker, W. Edelmann undA. Weiner, Ann. Chem.,719, 112 (1968).     

Markhacanasin C,cycloartane triterpenoid from the leaves of Markhamia stipulata var. canaense V.S. Dang

One new cycloartane triterpenoid, named markhacanasin C (1), together with three known triterpenoids, oleanolic acid (2), ursolic acid (3) and 6β,19α-dihydroxyursolic acid (4) were isolated by various chromatographic methods from the most cytotoxic fraction of the ethyl acetate extract of Markhamia stipulata var. canaense V.S. Dang leaves. Among them, 4 was reported for the first time from the genus Markhamia, while 2 and 3 were found for the first time from this species. Their structures were elucidated by IR, UV, HR-ESI-MS and NMR experiments. The cytotoxicity of isolated compounds (3 and 4) against three human cancer cell lines (HeLa, HepG2, and MCF-7) were evaluated. At the concentration of 100 μg/mL, 3 exhibited significant cytotoxic activity (86.36 ± 3.69%).     

Benzophenone glycosides from the pericarps of Aquilaria yunnanensis S. C. Huang

Abstract

Two new benzophenone glycosides, aquilarisides A (1) and B (2), together with six known analogues (3-8) were isolated from the pericarps of Aquilaria yunnanensis S. C. Huang. Their structures were elucidated on the basis of 1D and 2D NMR and mass spectroscopic analyses, and the absolute configuration of compound 1 was determined by experimental and calculated electronic circular dichroism (ECD) spectra. Anti-inflammatory activities of all compounds 1–8 were evaluated for their inhibitory activities against lipopolysaccharide (LPS)-stimulated induced nitric oxide (NO) production in RAW 264.7 cells using the Griess assay. Compound 2 indicated a weak inhibition of NO production.     

Über Reaktionen mit cyclischen Oxalylverbindungen, 6. Mitt.: Synthesen von Heterocyclen, 161. Mitt.

Zusammenfassung 4-Benzoyl-5-phenyl-2,3-dihydro-furan-2,3-dion (1) setzt sich mit Arylisocyanaten unter CO-Abspaltung zu den Oxazin-2,4-dionen3 bzw.4 um.1 und p-Tolylcarbodiimid reagieren hingegen zum 4-Hydroxy-chinolin9 weiter. Die 4-Hydroxy-chinoline9 bzw.17 erhält man unabhängig davon durch thermische Belastung der Pyrrol-2,3-dion-Derivate14 bzw.15, die aus den entsprechenden Dibenzoylmethananilen und Oxalylchlorid synthetisierbar sind. Als Zwischenstufen dieser Cyclisierungsreaktionen werden -Acylheterocumulene (2 bzw.12,19) postuliert.

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Reactions of cyclic oxalyl compounds, VI: Syntheses of heterocycles, CLXI

4-Benzoyl-5-phenyl-2.3-dihydro-furan-2.3-dione (1) reacts with aryl isocyanates with loss of CO to give the oxazine-2.4-diones3,4, resp. However, the reaction between1 and p-tolylcarbodiimide goes further, yielding the 4-hydroxyquinoline9. The quinolines9 and17 are obtained by an independent route by heating the pyrrole-2.3-diones14 and15, which can be synthesized from dibenzoylmethane aniles and oxalyl chloride. -Acylheterocumulenes (2,12,19, resp.) are postulated as intermediates for these cyclization reactions.

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Herrn Univ.-Prof. Dr.H. Nowotny, Vorstand des Inst. f. Physik. Chemie der Universität Wien, gewidmet.     

Elektrophile Substitution von Cymantrenen, 3. Mitt.: Methoxy-, Mercapto- und Thienocymantren (10. Mitt. über Cymantrenderivate)

Zusammenfassung Methoxycymantren (3) wurde aus Cymantren-diazoniumsulfat über das sehr oxydationsempfindliche Hydroxycymantren hergestellt. Das ebenfalls zur Oxydation neigende Mercaptocymantren (7) läßt sich bei O₂-Ausschluß nach Reduktion des Sulfochlorides5 isolieren.7 ergibt mit Dimethylsulfat Methylthiocymantren (9) und mit Chloressigsäure S-Cymantrenyl-thioglykolsäure (12). Aus12 ist durchFriedel-Crafts-Cyclisierung das Keton14 und daraus Thienocymantren (16) zugänglich. 3 und—in geringerm Maße-9 erwiesen sich bei derFriedel-Crafts-Acetylierung als -dirigierend. Die Acetylierung von Thienocymantren (16) ergibt ein Mono- und zwei Diacetylderivate. Die Strukturen wurden aus den NMR-Spektren und MS abgeleitet.

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Electrophilic substitution of cymantrenes, III: Methoxy-, mercapto-, and thieno-cymantrenes (cymantrene derivatives, X)

Methoxycymantrene (3) was prepared from cymantrene diazonium sulfate via (the very oxygen sensitive) hydroxycymantrene. Mercaptocymantrene (7), which is also prone to autoxidation, can be isolated, if O₂ is excluded, after reduction of the sulfonyl chloride5. 7 yields with dimethyl sulfate methylthiocymantrene (9). The reaction with chloroacetic acid produces S-cymantrenyl thioglycolic acid (12). From12 the ketone14 and thence thienocymantrene (16) is accessible by cyclisation.

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2. Mitt.:H. Egger undA. Nikiforov, Mh. Chem.99, 2311 (1968).

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9. Mitt.:H. Egger undA. Nikiforov, Mh. Chem.100, 483 (1969).     

Reaktionen mit phosphororganischen Verbindungen, 48. Mitt.

Reaction of the vicinal diols of steroids1, 5, 7, 10, 13, and16 with TPP/DEAD yields both regio-and stereospecifically the oxosteroids2, 6, 8, 11, 14, and15 by displacement of an axial hydrogen and extrusion ofTPPO besides the cholest-4-en-6-ols9 and12 and the cyclic carbonate3. 16, 17-androstandiol16 gives only the cyclic carbonate17. The different structures of the carbohydrates withcis-diol arrangement19 and21 lead exclusively to cyclic carbonates20 and22 in moderate yields. Treatment of1 with TPP/DEAD/HN₃ affords 3-azido-2-hydroxycholestane4 in addition to the above mentioned2.

     

Synthesen von Heterocyclen, 89. Mitt.

Zusammenfassung Isatosäureanhydrid (1) reagiert beim Verschmelzen mit Harnstoffen bzw. Thioharnstoffen zu Derivaten des Tetrahydrochinazolins (2 und3). Die Umsetzung kann auch in siedendemDMF durchgeführt werden.

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Isatoic anhydride (1) reacts with urea or thiourea yielding derivatives of tetrahydroquinazoline (2 and3). The reaction proceeds with good yields if the components are heated together without any solvent or in refluxingDMF.

     

Chemical composition and antioxidant activity of a polar extract of Thymelaea microphylla Coss. et Dur.

Thymelaea microphylla Coss. et Dur. (Thymelaeaceae) is a rare medicinal plant endemic to Algeria. In order to continue our studies on this species, herein we report the isolation and characterisation of 20 compounds from a hydroalcoholic extract (EtOH–H₂O 7:3) of the aerial parts. They include monoterpene glucosides (1–3), phenolic acid derivatives (4, 8 and 9), phenylpropanoid glucosides (5 and 6), flavonoids (7, 10 and 11), a benzyl alcohol glucoside (12), ionol glucosides (13–16), lignans (17–19) and a bis-coumarin (20). All the structures were elucidated by spectroscopic methods including 1D and 2D NMR experiments, as well as ESI-MS analysis. Moreover, the extract of T. microphylla showed a significant and concentration-dependent free radical-scavenging activity in vitro, correlated to the presence of phenolic and chlorogenic acid derivatives (8, 9 and 4).     

Über Reaktionen mit cyclischen Oxalylverbindungen, 8. Mitt.

Zusammenfassung Die aus den Enhydrazinen1 bzw.2 mit Oxalylchlorid synthetisierbaren Pyrrol-2,3-dione3 bzw.4 lagern sich bei therm. Belastung nach Art einerFischer-Indolsynthese in die Indolderivate5 bzw.6 um. 1-Diphenylamino-4-methyl-5-phenyl-2,3-dihydro-pyrrol-2,3-dion reagiert mit den entsprechenden nucleophilen Reagentien zu den Verbindungen7–9.

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Syntheses of heterocycles, CLXV: Reactions of cyclic oxalyl compounds, VIII

The enehydrazines1 and2 cyclize with oxalyl chloride yielding the pyrrole-2.3-diones3 and4, which can be rearranged to form the indole-derivatives5 and6 by heating. The 1-diphenylamino-4-methyl-5-phenyl-2.3-dihydro-pyrrole-2.3-dione reacts with the corresponding nucleophilic reagents to give the compounds7 to9.

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Meinem verehrten Lehrer, Herrn Prof. Dr.E. Ziegler, mit besten Wünschen zum 60. Geburtstag gewidmet.     

Derivate des Methylendioxybenzols, 28. Mitt.:

Zusammenfassung Es wird die Synthese der 2,5-Dimethoxy-3,4-methylendioxy- (1g), des 2,3-Dimethoxy-4,5-methylendioxy- (1h) und des 4,5-Dimethoxy-2,3-methylendioxy-phenols (1i) und ihrer Methyläther1j, k beschrieben. Weiterhin wird über die Darstellung des 2,3,6-Trimethoxy-4,5-methylendioxy-allylbenzols (1m) und die Synthese vondl-2-Amino-1-(dimethoxy-methylendioxyphenyl)-propan-Abkömmlingen (2d–f) berichtet.

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Derivatives of methylendioxy-benzene, XXVIII.: Reactions of the Dimethoxy-methylendioxy-benzaldehydes

Syntheses of 2.5-dimethoxy-3.4-methylenedioxy- (1g), 2.3-dimethoxy-4.5-methylenedioxy- (1h), and 4.5-dimethoxy-2.3-methylenedioxy-phenole (1i) and their methyl ethers1j, k and the preparation of 2.3.6-trimethoxy-4.5-methylenedioxy-allylbenzene (1m) and ofdl-2-amino-1-(dimethoxy-methylene-dioxyphenyl)-propane derivatives are described.

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Mitt.:F. Dallacker, Chem. Ber., im Druck.     

Über Dicyanmethylen-aminoindene,Indano-pyridazine und Indano-pyridine. Synthesen mit Nitrilen, 83. Mitt.

Summary 1-Dicyanomethylene-3-indanone (1) shows a remarkable reactivity of the carbonyl- and the methylene-function towards nucleophiles. With anilines and phenylhydrazine, resp., the deep-red colored pentamethinecyanines2 and3 are formed, azocoupling leads to indano-pyridazines4. With diphenylformamidines anilinomethylene-indanones5 are obtained in a primary reaction, followed by ring closure and Dimroth-rearrangement to indano-pyridines6.¹³C- and¹⁵N-NMR-spectrocopy is used for confirmation of the structures.

Herrn Prof. Dr. J. Schurz zum 65. Geburtstag gewidmet     

Functionalized C-Glycosyl Compounds. III. Reaction of Tertiary Nucleophiles with Unsaturated Carbohydrates. Mechanism of the Anomerization

Abstract

Phenyl 2, 3-dideoxy-4, 6-di-O-benzyl-D-erythro-hex-2-enopyranoside 1α (or 1β) is alkylated regio- and stereospecifically at the anomeric center by stabilized tertiary nucleo-philes in the presence of Pd(0) as a catalyst, leading to the C-glycoside of α- (or β-) configuration. The observed loss of stereoselectivity using secondary stabilized nucleophiles is mainly due to a retro Michael reaction. The assignment of the α- (or β-) configuration at the anomeric center was accomplished using ¹³C NMR and NOE experiments.     

Synthesen mit Nitrilen, 23. Mitt.

Zusammenfassung Die Bedingungen für die Kondensation von Benzil mit monomerem und dimerem Malonsäurenitril werden überprüft und für das 2-Benzoyl-2-phenyl-äthylen-1,1-dicarbonitril (2a) sowie das 2-Amino-4-benzoyl-4-phenyl-1,3-butadien-1,1,3-tricarbonitril (1a) die Strukturen sichergestellt. Unter dem Einfluß von wäßrigen Alkalien erleidet2a eine 1,2-Arylverschiebung und durch Cyclisierung entsteht das 2,5-Dioxo-4,4-diphenyl-pyrrolidin-3-carbonitril (7a).

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Syntheses with nitriles, XXIII.: Anionotropic 1,2-Shift of aryl groups in benzil-malononitrile condensation products

The condensation conditions of benzil with monomeric and dimeric malononitrile have been reinvestigated and the structures of 2-benzoyl-2-phenyl-ethylene-1.1-dicarbonitrile (2a) and 2-amino-4-benzoyl-4-phenyl-1.3-butadiene-1.1.3-tricarbonitrile (1a) elucidated. With aqueous alkali2 undergoes 1.2-arylmigration and cyclization yielding 2.5 dioxo-4.4-diphenyl-pyrrolidine-3-carbonitrile (7a).

     

Synthese von benzanellierten Carbacephamen, 1. Mitt.

Summary The direct intramolecular acylation and alkylation of the phenylsulfonylmethyl-group in the -lactames5a and7 are not successful. The postulated intermediate8 of the acylating reaction could be quenched with trimethylchlorosilane as the stable silylketale10. Desulfonation and desilylation of10 leads to the title compound12. The reaction of7 with base does not result in a carbacephame. Instead, the benzo[b]-azepinones15c,d have been obtained.

     

Markhasphingolipid A,new phytosphingolipid from the leaves of Markhamia stipulata var. canaense V.S. Dang

Abstract

From the leaves of Markhamia stipulata var. canaense V.S. Dang, one new phytosphingolipid, named markhasphingolipid A (6) together with five known compounds, 4’,7-O-dimethylapigenin (1), narigenin (2), tectoquinone (3), mollic acid (4), 1-hexadecanoyl-sn-glycerol (5) were classified by various chromatographic methods. Their structures were designated by IR, UV, HR-ESI-MS, HR-ESI-MS/MS and NMR experiments. All compounds were recognized for the first time from this species. The cytotoxicity of all n-hexane fractions and isolated compounds (5 & 6) against three human cancer cell lines (HeLa, HepG2, and MCF-7) were evaluated by SRB assay. All n-hexane fractions expressed cytotoxic effect on three tested cancer cell lines (at the concentration of 100?μg/mL, percent of cytotoxicity ranged from 55.81% to 95.83%) as well as compound 5 (IC₅₀ ranged from 48.51 to 63.30?μM) whereas fraction H.I and compound 6 did not show activity.

     

Two new phenolic compounds from the leaves of Alnus sibirica Fisch. ex Turcz.

Two new phenolic compounds, 4-O-glucopyranosyl-5-O-caffeoylshikimic acid (1) and 2,3-digalloyl oregonin (2), were isolated along with eight known phenolic compounds (3–10) from an 80% acetone extract of Alnus sibirica leaves. The chemical structures of these compounds were elucidated using 1D/2D nuclear magnetic resonance and high resolution-MS. The anti-oxidative activities of these compounds were determined by assaying their 1,1-diphenyl-2-picrylhydrazyl radical and nitroblue tetrazolium superoxide anion scavenging activity. All of the isolated phenolic compounds (1–10) exhibited potent anti-oxidative activities. In particular, 2 and 4, which are diarylheptanoids, and 10 which is ellagitannin exhibited excellent anti-oxidative activities with almost the same potency as that of the positive controls L-ascorbic acid and allopurinol.