Versuche zur Synthese von [2.2]- und [2.3]Cyclopentadienophanen

Synthetic Attempts towards [2.2]- and [2.3]Cyclopentadienophanes . The first [2.2]Cyclopentadienophane (=2,2,3,3,8,8,9,9-octamethyltricyclo[8.2.1.1^4,7]tetradecatetraene; 1b ) has been synthesized (Scheme 5) by reductive coupling of 6,6-dimethylfulvene 3 → 5 (50%) followed by base-induced twofold condensation of 1,2-di(cyclopentadienyl)-1,2-dimethylbutane 5 with acetone to give difulvene 15 (95%). Reductive coupling of 15 gives a complex mixture of tautomers of 16 , 17 , and 1b , which contains ca. 50% of the target molecule 1b . Other synthetic attempts towards [2.2]cyclopentadienophanes 1a and 1b and [2.3]cyclopentadienophane 18 are discussed.     

Comparison of iodinated [Nle15]- and [Met15]-gastrin17 prepared by reversed-phase HPLC

125I-[Nle15]-gastrin17 prepared by the iodogen method can be separated by reversed-phase high performance liquid chromatography into two peaks, both of which elute after [Nle15]-gastrin17. Direct determination of the specific activities of the two derivatives by microbore reversed-phase HPLC indicated that they were the mono- and di-iodinated species. In contrast the two peaks obtained with [Met15]-gastrin17 iodinated under the same conditions eluted earlier, relative to the appropriate gastrin17 standard, than the [Nle15]-gastrin derivatives. Treatment of either peak with 0.75 M dithiothreitol at 56 degrees C or 95 degrees C resulted in progressive conversion to compounds migrating in relative positions similar to the 125I-[Nle15]-gastrin17 derivatives. Direct determination of the specific activity of the earlier eluting [Met15]-gastrin17 derivative before reduction indicated that it was the mono-iodinated species. It thus appears likely that iodination of [Met15]-gastrin17 by the iodogen method results predominantly in the formation of mono- and di-125I-[Met sulphoxide15]-gastrin17. To avoid problems arising from oxidation of the methionine residue of gastrin during iodination, the use of 125I-[Nle15]-gastrin17 in binding studies is therefore recommended.     

Self－assembly of Novel Hetero[3]rotaxane, [2]Rotaxanes and [2]Catenane

One linear template 13 and one cyclophane template 15, both incorporating two electron rich 1,4‐dialkoxybenzene units and one diamide unit, have been synthesized. By utilizing donor‐acceptor interaction and/or intermolecular hydrogen bonding assembling principles, one novel hetero[3]rotazane 22·4Cl, possessing one neutral and one tetracationic ring components, has been synthesized from 13, through neutral [2]rotaxane 21 as intermediate. With 15 as template, tetracationic [2]catenane 23·4PF₆ was assembled by using donor‐acceptor interaction, but no neutral [2]rotaxane could be obtained under the typical conditions of hydrogen bonding assembling principle. The interlocked supramolecular compounds have been characterized and their spectral properties are investigated.     

Synthesis and cytotoxic activity of benzo[a]pyrano[3,2-h] and [2,3-i]xanthone analogues of psorospermine, acronycine, and benzo[a]acronycine

Condensation of 2-hydroxy-1-naphthalenecarboxylic acid with phloroglucinol afforded 9,11-dihydroxy-12H-benzo[a]xanthen-12-one (6). Construction of an additional dimethylpyran ring onto this skeleton, by alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement, gave access to 6-hydroxy-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (12) and 5-hydroxy-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (13), which were methylated into 6-methoxy-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (14) and 5-methoxy-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (15), respectively. Osmium tetroxide oxidation of 14 and 15 gave the corresponding (+/-)-cis-diols 16 and 17, which afforded the corresponding esters 18-21 upon acylation. Similarly, condensation of 2-hydroxy-1-naphthalenecarboxylic acid with 3,5-dimethoxyaniline gave 11-amino-9-methoxy-12H-benzo[a]xanthen-12-one (23) which was converted into 11-amino-9-hydroxy-12H-benzo[a]xanthen-12-one (24) upon treatment with hydrogen bromide in acetic acid. Alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement afforded 6-amino-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (25) and 5-amino-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (26). The new benzopyranoxanthone derivatives only displayed marginal antiproliferative activity when tested against L1210 and KB-3-1 cell lines. The only compounds found significantly active against L1210 cell line, 16 and 20, belong to the benzo[a]pyrano[3,2-h]xanthen-7-one series, which possess a pyran ring fused angularly onto the xanthone basic core.     

Differentiation between [1,2,4]triazolo[1,5‐a] pyrimidine and [1,2,4]triazolo[4,3‐a]‐ pyrimidine regioisomers by 1H?15N HMBC experiments

The condensation of malonoaldehyde derivatives with either a 3‐amino‐[1,2,4]‐triazole or a 3,5‐diamino‐[1,2,4]‐triazole precursor was studied. In agreement with previous reports, two different bicycles, namely, bearing the regioisomeric [1,2,4]triazolo[1,5‐a]pyrimidine ( 1 ) or[1,2,4] triazolo [4,3‐a]pyrimidine ( 2 ) structural surrogates, could be obtained. We found that, depending on the triazole precursor, only one regioisomer resulted, either of the 1 or 2 series. We also observed that these two structural surrogates could be unambiguously differentiated by indirectly measuring their ¹⁵N chemical shifts by ¹H? ¹⁵N HMBC experiments. The occasional conversion of [1,2,4]triazolo[4,3‐a]pyrimidines to the [1,2,4]triazolo[1,5‐a]pyrimidine counterparts could be unequivocally determined by ¹⁵N NMR data. Copyright © 2010 John Wiley & Sons, Ltd.     

Syntheses of Examples of the 5,6-dihydro-4H-[1,2,3]triazolo[4,5,1-ij]quinoline, 4,5,6,7-tetrahydro[1,2,3]triazolo[4,5,1-jk][1,4]benzodiazepine,and 5,6,7,8-tetrahydro-4H-[1,2,3]triazolo[4,5,1-kl][1]benzazocine ring systems

Lithiation of 1-vinylbenzotriazole 9 with n-BuLi (2 equiv) generates dianion 10, which upon subsequent reaction with 1,2- and 1,4-diketones affords 14 and 13, representatives of the 5,6-dihydro-4H-[1,2,3]triazolo[4,5,1-ij]quinoline 1 and 5,6,7,8-tetrahydro-4H-[1,2,3]triazolo[4,5,1-kl][1]benzazocine 2 ring systems, respectively. Reactions of dianion 10 with isocyanates give 15a,b, which contain the 4,5,6,7-tetrahydro[1,2,3]triazolo[4,5,1-jk][1,4]benzodiazepine 3 ring system.     

Ultrahigh-resolution capillary electrophoretic separation with indirect ultraviolet detection: isotopic separation of [14N]- and [15N]ammonium.

Separation of isotopically labeled [14N]/[15N] ammonium was performed with capillary electrophoresis. This ultrahigh-resolution separation was based on mobility counterbalance with precise control of the anodic electroosmotic flow. Mixtures of zwitterionic surfactant (Rewoteric AM CAS U) and cationic surfactant (cetyltrimethylammonium bromide) were used as buffer additives to modify the electroosmotic mobility. Indirect ultraviolet detection was used with benzyltributylammonium as the buffer coion. Baseline-resolved peaks of [14N]- and [15N]ammonium were obtained within 11 min. The detection limit was 0.01 mM for both [14N]-and [15N]ammonium. Linear calibration in concentration was observed up to 1.0 mM for [15N]ammonium and 2.0 mM for [14N]ammonium. Calibration of the isotopic ratio, [15N]ammonium concentration to total ([14N] and [15N])ammonium, was valid from 5 to 95%.     

Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols

Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 were reacted with NBS in wet DMSO to afford bromohydrins. Mixtures of unrearranged 6-exo-bromo-5-endo-hydroxy-2-azabicyclo[2.2.0]hexanes 7a,b and rearranged 5-anti-bromo-6-anti-hydroxy-2-azabicyclo[2.1.1]hexanes 8a,b were formed stereoselectively from the parent alkene 6a and 4-methyl alkene 6b. The 5-methyl alkene 6c affords only unrearranged bromohydrin 7c and dibromohydrin 9. By contrast, solely rearranged 3-endo-substituted-2-azabicyclo[2.1.1]hexane bromohydrins 8d-f result from additions to 3-endo-methyl alkene 6d, 3-endo-4-dimethyl alkene 6e, and 3-endo-phenyl alkene 6f. As an alternative route to bromohydrins, the parent 5,6-exo-epoxide 10a and 5-endo-methyl-5,6-exo-epoxide 10b were ring opened with bromine/triphenylphosphine to afford unrearranged 5-endo-bromo-6-exo-hydroxy-2-azabicyclo[2.2.0]hexanes 11a,b, while the 3-endo-methyl epoxide 10c afforded solely the rearranged 5-anti-bromo-6-anti-hydroxy-3-exo-methyl-2-azabicyclo[2.1.1]hexane isomer 8g. Tributyltin hydride reduction of bromohydrins 7a,b and 11a afforded novel 2-azabicyclo[2.2.0]hexan-5-ols 13a,b and -6-ol 14, and bromohydrins 8a,b, 8d-g afforded new 2-azabicyclo[2.1.1]-hexan-5-ols 15a,b and 15d-g.     

Synthesis of [1,2,4]triazoloquinazoline and [1,2,4]-triazolo-1,4-benzodiazepine derivatives

Some [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-ones 7 , the corresponding isomers [1,2,4]triazolo[4,3-c]quinazo-lin-5(6H)-ones and the 5-amino derivatives 8, 9 and 11 have been synthesized starting from the acylamidrazones 5 . The preparation of 5H-[1,2,4]triazolo[1,5-d]-1,4-benzodiazepin-6(7H)-ones 15 and of 5-cyclicaminomethyl-[1,2,4]triazolo[1,5-c]quinazolines 16 and 17 is also reported.     

Tetraphenylethene-Embedded Pillar[5]arene and [15]Paracyclophane: Distorted Cavities and Host–Guest Binding Properties

Two aggregation-induced emission (AIE) macrocycles (DMP[5]-TPE and PCP[5]-TPE) were prepared by embedding Tetraphenylethene (TPE) unit into the skeletons of Dimethoxypillar[5]arene (DMP[5]) and [15]Paracyclophane ([15]PCP) at meso position, respectively. In crystal, the PCP[5]-TPE showed a distorted cavity, and the incubation of hexane inside the DMP[5]-TPE cavity caused a distinct change in the molecular conformation compared to PCP[5]-TPE. There was no complexation between PCP[5]-TPE and 1,4-dicyanobutane (DCB). UV absorption experiments showed the distorted cavity of DMP[5]-TPE hindered association with DCB.     

2]Catenane assembly from calix[4]arene crown ethers [In Process Citation

A variety of novel calix[4]arene-incorporating crown ethers with or without intramolecular hydrogen bonding have been prepared by two efficient methods and utilized as donor rings to assemble calix[4]arene [2]catenanes based on pi-stacking interaction between hydroquinone and bipyridinium units. Treatment of calix[4]arene crown ethers 4, 10a, or 10b, whose cone conformation was fixed by intramolecular hydrogen bonding within the calix[4]arene moiety, with dicationic salt 15 x 2PF6 and dibromide 16 afforded the corresponding [2]catenanes 17a x 4PF6, 17b x 4PF6, and 17c x 4PF6 in 20%, 53%, and 55% yields, respectively, whereas from the reactions of 15 x 2PF6 and dibromide 16 in the presence of conformationally flexible 11 or 12 with a cone conformation kept by two propyl groups, [2]catenanes 18 x 4PF6 and 19 x 4PF6 were obtained in 12% and 6% yields. [2]Catenanes 21a x 4Cl, 21b x 4Cl, and 21c x 4Cl, incorporating calix[4]arene in both the donor and acceptor rings, were also successfully assembled from 10a or 10b, 16, and dicationic salts 20a x 2PF6 or 20b x 2PF6. The dynamic 1H NMR and absorption spectra of the [2]catenanes have been investigated, which revealed a strongest donor-acceptor interaction in 17a x 4PF6 and that the cone [2]catenanes 17a-c x 4PF6 can isomerize to the partial cone isomer at high temperature. The difference of the dynamic properties of these catenanes was discussed. The results demonstrate that catenation is one new general method to change the conformational distributions of calix[4]arenes.     

Conversion of 3,n-dithiabicyclo[n.3.1]alkatrienes to bicyclo[n.3.1]alkapentaenes

The application of the Ramberg-Backlund reaction in the conversion of several 3,n-dithiabicyclo[n.3.1]alkatrienes to the corresponding bicyclo[n.3.1]alkapentaenes is reported. Proton magnetic resonance and ultraviolet spectra were utilized in the overall characterization of bicyclo[8.3.1]tetradeca-2,8,10,12,1(14)-pentaene, bicyclo[9.3.1]pentadeca-2,9,11,1(15)-pentaene, and their precursors. The final step in the synthesis was a Ramberg-Backlund of bis-α,α′-chloro sulfone. The intermediate, 2-chloro-3-thiabicyclo[9.3.1]pentadeca-9,11,13,1(15)-tetraene 3,3-dioxide, was isolated and characterized. The structure and stability of the bridged α,α′-dichloro sulfide intermediates were examined.     

Synthesis of [1]benzopyrano[3,4-b] [1,4]oxazines as potential antidepressants

Stereospecific syntheses, from Δ-3-chromene, of cis and trans-4-aminochroman-3-ols, 5 and 8 , and their conversion into cis and trans-1,2,3,4a,5,10b-hexahydro[1]benzopyrano[3,4-b][1,4]-oxazines, 15 and 16 , are described.     

Synthesis of a linear benzo[3]phenylene-[60]fullerene dyad

The synthesis of a new linear benzo[3]phenylene-[60]fullerene dyad 1 is achieved over 10 steps in 15% overall yield by using an efficient sequence combining a double cobalt(I)-mediated cyclotrimerization with a Bingel reaction.     

The synthesis of monomethoxy[1]benzothieno[2,3-c]quinolines

A series of monomethoxy[1]benzothieno[2,3-c]quinolines 24-28 were prepared by photocylization of the appropriate 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamides 9–13 to [1]benzothieno[2,3-c]quinolin-6(5H)-ones 14-18 followed by chlorination to 6-chloro[1]benzothieno[2,3-c]quinolines 19-23 then dechlorination resulting in the title compounds except for 25 which was achieved by direct reduction of 15 . Reaction of 24-28 with methyl iodide provided the corresponding N-methyl quaternary salts 29-33 . Also, conversion of 4-meth-oxy[1]benzothieno[2,3-c]quinolin-6(5H)-one 16 to 4-methoxy-6-methylthio[1]benzothieno[2,3-c]quinoline 35 and 4,6-dimethoxy[1]benzothieno[2,3-c]quinoline 36 is described.     

Synthesis and characterization of [1,2,5]chalcogenazolo[3,4-f]benzo[1,2,3]triazole and [1,2,3]triazolo[3,4-g]quinoxaline derivatives

The synthesis and characterization is reported of low bandgap [1,2,5]chalcogenazolo[3,4-f]benzo[1,2,3]triazole and [1,2,3]triazolo[3,4-g]quinoxaline derivatives that display higher solubility and stability then their thiadiazole counterparts, [1,2,5]chalcogenazolo[3,4-f]benzo[2,1,3]thiadiazole and [1,2,5]thiadiazolo[3,4-g]quinoxaline, respectively.     

An Efficient Synthesis of [15N]-Carbazole from [15N]-Aniline

A reaction sequence involving ortho-lithiation of [¹⁵N]-(tert-Butoxy-carbonyl)aniline, quenching with Bu₃SnCl, palladium catalyzed coupling with bromobenzene, and deprotection provides efficient access to [¹⁵N]-2-aminobiphenyl (4). Compound 4 is converted to [¹⁵N]-carbazole via diazotization, treatment with NaN₃, and heating to promote intramolecular nitrene insertion.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 9. Phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,and benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline

The synthesis of three novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 13 ), benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 14 ), and benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 15 ).     

Synthèse,réduction chimique et électrochimique de benzopyranno[1][4,3-e] et [3,4-e]pyrimido[1,2-b]-as-triazinones

From 9H-amino [l]benzopyranno-as-triazines 2 and 3 , [l]ben-zopyranno[4,3-e] or [3,4-e]pyrimido[l,2-b]-as-triazinones have been prepared by reaction with β-ketoesters. Chemical reduction of the compounds gives tetrahydro derivatives. By electrochemical reduction the dihydro compounds 14 and 15 were from-ed. The same dihydro derivatives were obtained with Grignard reagents.     

Synthesis and cytotoxic activity of acronycine analogues in the benzo[c]pyrano[3,2-h]acridin-7-one and naphtho[1,2-b][1,7] and [1,10]-phenanthrolin-7(14H)-one series

Condensation of 1-bromo-2-naphthalenecarboxylic acid (9) with 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine (13) followed by acid-mediated cyclization afforded 6-methoxy-3,3-dimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (15), which was further methylated into 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (benzo[c]acronycine) (3) and 6,7-dimethoxy-3,3-dimethyl-3H-benzo[c]pyrano[3,2-h]acridine (4). Osmium tetroxide oxidation of 15 gave the (+/-)-cis-diol 16, which afforded the benzopyranoacridine and benzopyranoacridone esters 17-22 upon acylation. Condensation of 9 with suitable aminoquinolines 23-25 afforded the carboxylic naphthylquinolylamines 26-28. Cyclization gave the corresponding naphtho[1,2-b][1,10]-phenanthrolin-7(14H)-ones 29 and 30, and naphtho[1,2-b][1,7]-phenanthrolin-7(14H)-one 31, which were subsequently N-methylated to the desired 14-methylnaphtho[1,2-b][1,10] and [1,7]-phenanthrolinones 6, 7, and 8. Benzo[c]pyrano[3,2-h]acridin-7-one derivatives 3, 16, and 22 displayed cytotoxic activities within the same range of magnitude as acronycine itself, whereas 7-alkoxybenzo[c]pyrano[3,2-h]acridine and 7-acyloxybenzo[c]pyrano[3,2-h]acridine derivatives 4 and 17-21 were less active when tested against L1210 murine leukemia cells in vitro. Naphthophenanthrolinones 6-8 were devoid of significant antiproliferative activity, but compounds 29-31 bearing no substituent on the nitrogen atom at position 14 were more potent.