Synthesis and reactions of 3-carboxytropolone. Conversion to heterocycle-fused troponoid compounds

The haloform reaction of 3-acetyltropolone ( 1 ) afforded 3-carboxytropolone ( 2 ) which was treated with diazomethane to give 2-methoxy-3-methoxycarbonyltropone (3a) and 2-methoxy-7-methoxycarbonyltropone (3b). The tropolone 2 reacted with hydrazine to afford 2-hydrazino-3-hydrazinocarbonyltropone ( 10 ) or 2-hydrazinotropone ( 11 ), depending on the reaction time. The reaction of 2 with phenylhydrazine produced 3-hydroxy-1-phenyl-1,8-dihydrocycloheptapyrazol-8-one (14). The treatment of 2-methoxy-3-methoxycarbonyltropone (3a) with hydrazine or phenylhydrazine gave cyclization products 12 and 15 , respectively. The reaction of 2-methoxy-7-methoxycarbonyltropone (3b) with hydrazine, phenylhydrazine, or methylhydrazine gave 2-hydrazino- ( 13 ), 2-(2-phenylhydrazino)- ( 16 ), and 2-(2-methylhydrazino)-7-methoxycarbonyltropone ( 17 ), respectively.     

New helerocyclic ring systems from α-llydroxymethylenekelones. VIII. Polyuzasteroidal analogues of equilenin

Some 6, 15,16-triazasteroidal analogues of Equilenin carrying a 7-methyl substituent have been synthesized from 4-methyl-7-methoxy-10,11]-dihydroisoxazolo[5,4-i]phenanthridine (III).     

Reactions of ethyl β-methoxycrotonate with some α,β-unsaturated carbonyl compounds. Synthesis of 6-aroyl-5-aryl-3-methoxycyclohex-2-enones

3-Aryl-1-phenyl-2-propen-1-ones Ia-h and 1-aryl-3-phenyl-2-propen-1-ones Ii-ℓreacted with ethyl β-methoxy-crotonate (II) in the presence of sodium hydride in dry THF at 0° for 10 hours to give the corresponding 6-aroyl-5-aryl-3-methoxy-2-cyclohexen-1-ones III. The structures of the products were confirmed by ir, pmr, ¹³C nmr and uv spectroscopy.     

Polyfluorinated heterocyclic compounds

The treatment of 2-phenyl-4-carbomethoxy-6,7,8,9-tetrafluorobenz[f]oxazepin-1,3 (I), 3-benzamido-5,6,7,8-tetrafluorocoumarin (V), and α-benzamido-β-(2-hydroxy-3,4,5,6-tetrafluorophenyl)-acrylic acid (III) with a mixture of glacial acetic acid and a mineral acid gave (IV), the π-complex of 3-hydroxy-5,6,7,8-tetrafluorocoumarin (VII) and benzoic acid. Treatment of (IV) with acetic anhydride gave 3-acetoxy-5,6,7,8-tetrafluorocoumarin (VI) and benzoic acid. Treatment with diazomethane gave 3-methoxy-5,6,7,8-tetrafluorocoumarin (VIII) and methyl benzoate. IV was also obtained from an equimolar mixture of its components. A mechanism for the formation of IV from I is proposed.     

Neue Sulfonamide, 14. Mitt.: Zwei weitere Synthesen des 6-Sulfanilamido-2,4-dimethoxy-pyrimidins (Sulfadimethoxins)

Zusammenfassung Es werden die neuen Verbindungen 6-Sulfanilamido-2-methoxy-4-chlorpyrimidin (III), 6-Sulfanilamido-2,4-dichlorpyrimidin (VII) und 6-Sulfanilamido-2-methoxy-4-dimethylamino-pyrimidin (VIII) mittels Sulfanilamidolyse dargestellt. III und VII lassen sich leicht in 6-Sulfanilamido-2,4-dimethoxypyrimidin (IV) überführen.Vgl. vorläuf. Mitt.: Mh. Chem.92, 75 (1961).13. Mitt., Mh. Chem.95, 102 (1964).     

3个新呋喃黄酮的NMR研究

从厚果难血藤（Millettia pachycarpa Benth)根中分离得到3个呋喃黄酮类化合物,经NMR谱等分析研究,确定了它们的结构为：4H－呋喃并[2,3-h][1]苯并吡喃－4－酮,3－甲氧基－2－（3,4,5－三甲氧基苯基）（I）、4H－呋喃并[2,3-h][1]苯并吡喃－4－酮,3－甲氧基－2（3－甲氧苯基）（Ⅱ）、10,11二甲氧基－[2]苯并吡喃[4,3-b]-呋喃并[2,3-h][1]苯并吡喃－6（8H）－酮（Ⅲ）,皆未见文献报道,分别命名为厚果鸡血藤丙素（pachycarin C)、厚果难血藤丁素（pachycarin D)和厚果鸡血藤戊素（pachycarin E)。     

Synthesis of 4-methoxy-2,3,5-trimethylpyridine: a specific building block for compounds with gastric-acid inhibiting activity

A new synthesis of 4-methoxy-2,3,5-trimethylpyridine (2), an important building block for the preparation of gastric-acid inhibiting compounds, is described. Condensation of ethyl 3-amino-2-methyl-2-butenoate (3) and diethyl 2-methylmalonate (4) gives 4-hydroxy-3,5,6-trimethyl-2(1H)-pyridone 5. Reaction of 5 with phosphoryl chloride affords 2,4-dichloro-3,5,6-trimethylpyridine (9a), which, upon hydrogenolysis with palladium on charcoal, gives 2,3,5-trimethylpyridine (10). However, selective hydrogenolysis in acidic solution yields 4-chloro-2-3-5-trimethylpyridine (11). Substitution of the chlorine in 11 with methoxide ion gives 4-methoxy-2,3,5-trimethylpyridine (2), which can be oxidized to the corresponding N-oxide (13). This constitutes a new and efficient route to compound 2 in an overall yield of 43%.     

Synthesis of 3-dialkylaminochromans via thallium(III)-induced cyclization of allyl aryl ethers

The sulfur-containing 3-alkylaminochromans, 5-methoxy-3-[N-(2- methylthioethyl)-propylamino]chroman (15), 5-hydroxy-3-[N-(2-methylthioethyl)propylamino]chroman (5) and 5-methoxy-8-methylthio-3-(dipropylamino)chroman (6), have been prepared from 8-bromo-5-methoxy-3-chromanol (11). This precursor was synthesized from 3-allyloxy-4-bromoanisole (8), by a thallium(III)-mediated ring-closure reaction. Compound 11 also served as starting material for the synthesis of 8-bromo-3-(dipropylamino)-5-methoxychroman (7).     

Studies on the syntheses of heterocyclic compounds. CDXCI pyrimidine derivatives V. Abnormal condensation products of 4-amino-6-chloro-2-methoxypyrimidine with p-nitrobenzenesulfonyl chloride

Condensation of 4-amino-6-chloro-2-methoxypyrimidine (I) with p-nitrobenzenesulfonyl chloride (II) gave, in addition to 6-chloro-2-methoxy-4-(p-nitrobenzenesulfonamido)pyrimidine (III), two abnormal by-products, the structures of which were assigned as 1 -[2-methoxy-4-(p-nitrobenzenesulfonamido)pyrimidine-6-yl]pyridinium N,N-betaine (IV) and N-(p-nitrobenzene-sulfonyl)-β-ureido-β-pyridinium acrylamide N,N-betaine (V).     

Studies on the constituents of Anaxagorea luzonensis A. GRAY

Five new xanthones, 1,3,6-trihydroxy-5-methoxy-4-prenylxanthone (1), 1,3,5-trihydroxy-6-methoxy-2-prenylxanthone (2), 1,3,5-trihydroxy-4-(3-hydroxy-3-methylbutyl) xanthone (3), 1,3,6-trihydroxy-4-prenylxanthone (4), 3,6-dihydroxy-1,5-dimethoxyxanthone (5) and one new flavonoid, 3,5,7,4'-tetrahydroxy-2'-methoxyflavone (6) along with seven known xanthones and seven known flavonoids were isolated from the bark of Anaxagorea luzonensis A. GRAY and their chemical structures were determined by means of chemical and spectral studies. Almost all flavonoids and one xanthone (13) showed antioxidant activity.     

Studies on the syntheses of analgesics. Part XXXI. Synthesis of 1,2,3,4,5,6-Hexahydro-3-methyl-6-phenyl-2,6-melhano-2,3-benzo[g] diazocine [studies on the syntheses of heterocyclic compounds. Part CDLXXIX]

1,2,3,4,5,6 Hexahydro-8-methoxy-3-methyl-6-phenyl-2,6-methano-2,3-benzo[g]diazocine (IIa) was synthesized from 1-(3-methoxyphenyl)phenylaeetonitrile (III), readily available by the benzyne reaction of o-chloroanisole with phenylacetonitrile, through several steps. Treatment of IIa with 47% hydrobromic acid afforded 1,2,3,4,5,6-hexahydro-8-hydroxy-3-methyl-6-phenyl-2,6-methano-2,3-benzo[g]diazocine (IIb).     

Phenolic compounds from Anaphalis aureo-punctata

From the ethanolic extract of the whole plant of Anaphalis aureo-punctata, a new acylated flavonoid glycoside 3-O-kaempferol-3-O-acetyl-6-O-(p-coumaroyl)-β-D-glucopyranoside (1), and five known phenolic compounds 3-O-kaempferol-6- O- ( p-coumaroyl )-β-D-glucopyranoside ( 2 ), kaempferol-3- O-β-D-glucopyranoside 3,6-(4′-hydroxystyryl)-4-methoxy-2-pyrone (4), 2H-pyran-2-one, 6-[ 2-( 4-(β-D-glucopyranosyloxy ) phenyl ) ethenyl ]-4-methoxy-( E ) (5) and 4-hydroxy-3-methoxycinnamic hexacosyl ester (6) were isolated. Their structures were established by spectral methods (UV, IR, MS, 1D, 2D-NMR). The flavonoid glycosides, 1, 2 and 3 showed markedly inhibited oxidative DNA strand breaks induced by Fenton reaction and NADH/PMS in a concentration-dependent manner.     

Bioactivity-guided isolation of new antiproliferative compounds from Juniperus foetidissima Willd.

Based on a literature survey on cytotoxic medicinal plants, Juniper species were identified as interesting source of antitumor compounds. Using bioassay-guided fractionation against Caov-4 cancer cells on acetone extract of leaves and branchlets of Juniperus foetidissima led to the isolation of a new 3H-benzofuaran-2-one: 4-methyl-3-methoxy-3H-benzofuaran-2-one (1), a new sesquiterpene: 4,9(α)-dihydroxy-nardosin-6-en (2) and an already known labdane-type diterpene: 15-hydroxy-8(17),13(E)-labdadiene-19-carboxilic acid (3). Compounds 1–3 exhibited cytotoxic effects, with moderate cytotoxicity against the EJ-138 bladder and CAOV-4 ovary cancer cell lines.     

Studies on the syntheses of heteroeyelie compounds. Part DV. Cyclization products of i-substituted 2-benzyl-1,2,5,6-tetrahydropyridines [syntheses of analgesics. Part XXXV]

Treatment of 1,2,5,6-tetrahydro-2-(4-hydroxy- and/or 4-methoxybenzyl)-3,4-dimethyl-I-(3-methyl-2-butenyl)pyridines (IV and V) and 2-(4-methoxybenzyl)-3,4-dimethyl-1-(3-methyl-2-butenyl)-4-piperidinol (X) with acid afforded 9-(4-hydroxy- and/or 4-methoxybenzyl)-4,4,5,6-tetramethyl-1-azabicyelo[3,3,1]non-6-ene (XIII and XIV). In contrast, the corresponding 1-allyl-substituted derivatives VI, VII, and XI were converted into the expected 3-allyl-1,2,3,4,5,6-hexahydro-8-hydroxy- and/or 8-methoxy-6,11-dimethyl-2,6-methano-3-benzazocine (II and III).     

Quinone-type podocarpanes from the bark of Taiwania cryptomerioides

Three quinone-type podocarpanes, 3beta-hydroxy-13-methoxy-8,12-podocarpadiene-11,14-dione (1), 18-hydroxy-13-methoxy-8,12-podocarpadiene-11,14-dione (2), and 13-methoxy-8,12-podocarpadiene-2,11,14-trione (3) were isolated from the bark of Taiwania cryptomerioides. Their structures were elucidated using spectral methods.     

Condensation reactions of a comenaldehyde derivative

Condensation reactions of comenaldehyde methyl ether (I) with malonic acid, ethyl cyanoacetate, and cyanoacetamide to give β-(5-methoxy-4H-pyran-4-on-2-yl)acrylic acid (II), ethyl 2-cyano-3-(5-methoxy-4H-pyran-4-on-2-yl)propenoate (III), and 2-cyano-3-(5-methoxy-4H-pyran-4-on-2-yl)propenamide (IV), respectively, are described. Ultraviolet absorption spectra for 2-hydroxymethyl-5-methoxy-4H-pyran-4-one, I and II are presented.     

Synthesis and reactions of halo-, nitro-, and arylazo-substituted 3-cinnamoyltropolones. Formation of styryl-substituted heterocycle-fused troponoid compounds

3-Cinnamoyltropolone ( 1 ) reacted with bromine to afford 7-bromo- ( 2 ), 5,7-dibromo-3-cinnamoyltropolone ( 3 ), and 6,8-dibromo-4,9-dihydrocyclohepta[b]pyrane-4,9-dione ( 4 ) according to amount of the reagent. Iodination and nitration of 1 gave respectively 7-iodo- ( 5 ) and 5-nitro-3-cinnamoyltropolone ( 6 ). Azo-coupling reactions gave 5-arylazo-3-cinnamoyltropolones 7a-f . Compounds 1, 2, 3 and 5 reacted with hydroxylamine to give 3-styryl-8H-cyclohept[d]isoxazol-8-ones 10-13 , while 6 and 7a gave 5-nitro-3-styryl-8H-cyclohept[d]-isoxazol-8-one oxime ( 14 ) and 2-cinnamoyl-7-methoxy-4-phenylazotropone ( 15 ), respectively. The reactions of 1,3 , and 5 with phenylhydrazine gave 3-styryl-1,8-dihydrocycloheptapyrazol-8-ones 16-19 .     

Polyfluorinated heterocyclic compounds

The treatment of 2-phenyl-4-carbomethoxy-6,7,8,9-tetrafluorobenz[f]oxazepin-1,3 (I), 3-benzamido-5,6,7,8-tetrafluorocoumarin (V), and -benzamido--(2-hydroxy-3,4,5,6-tetrafluorophenyl)-acrylic acid (III) with a mixture of glacial acetic acid and a mineral acid gave (IV), the -complex of 3-hydroxy-5,6,7,8-tetrafluorocoumarin (VII) and benzoic acid. Treatment of (IV) with acetic anhydride gave 3-acetoxy-5,6,7,8-tetrafluorocoumarin (VI) and benzoic acid. Treatment with diazomethane gave 3-methoxy-5,6,7,8-tetrafluorocoumarin (VIII) and methyl benzoate. IV was also obtained from an equimolar mixture of its components. A mechanism for the formation of IV from I is proposed.For part II, see [1].     

Streptonigrin and related compounds IV. Precursors for the a-ring

The synthesis of streptonigrin or its tricyclic (ABC) analogues by the Friedlander condensation requires a 2-nitrobenzaldehyde with all the necessary functionalities. A number of alternative syntheses are examined. It is shown that oxidation of 8-amino-5,6-dimethoxy-2,2-pyridylquinoline leads to 8-amino-2,2-pyridylqunoline-5,6-dione instead of 6-methoxy-2,2-pyridylquinoline-5,8-dione. The synthesis of two useful precursors: 4-bromo-3-hydroxy-5,6-dimethoxy-2-nitrobenzaldehyde and 4-bromo-3-hydroxy-5-methoxy-2-nitrobenzaldehyde is described.     

Electron-impact induced skeletal re-arrangement of 2-methoxy-3-methylpyrazine and 2-methylthio-3-methylpyrazine

The mass spectra of 2-methoxy-3-methylpyrazine (I), 2-methoxy-6-methylpyrazine (II), 2-methylthio-3-methylpyrazine (III) and 2-methylthio-6-methylpyrazine (IV), are given and the major fragmentation pathways discussed. The novel loss of H₂O from the molecular ion of I and the corresponding loss of H₂S from the molecular ion of III indicate that a skeletal rearrangement takes place in the molecular ion preceding the expulsion of H₂O and H₂S. Proposed mechanisms for this behavior are discussed with evidence being drawn from accurate mass measurement, metastable ions, and deuterium and carbon-13 labeling of the methoxy group. The absence of ions in the spectra of II and IV corresponding to the loss of H₂O and H₂S from these molecular ions clearly indicates that the position of the methyl group with respect to the methoxy group, or the methylthio group is in-timately involved in this mechanism.