The Effects of β-Cyclodextrin On the Fluorescence,Uv Absorption and Solubility of Selected Bimanes In Aqueous Solutions

Abstract

The effects of β-cyclodextrin were investigated on the fluorescence emission and excitation as well as on the UV absorption and solubility of certain bimanes in aqueous solution. Three syn-bimanes with differing water solubilities were examined, namely, syn-(CH₂OCOCH₃, CH₃) bimane, syn-(CH₃, CH₃) bimane, and syn-(C₆H₃, Cl) bimane. the anti-(CH₃, CH₃) bimane was also examined. In dilute solutions, the syn-(CH₃, CH₃) bimane and syn-(C₆H₃, Cl) bimane showed enhancement of their relative fluorescence intensities upon the addition of β-cyclodextrin as did anti-(CH₃, CH₃) bimane. Only the anti-(CH₃, CH₃) bimane showed significant changes in its UV absorption upon the addition of β-cyclodextrin. Both syn-(CH₂OCOCH₃, CH₃) bimane and syn-(CH₃, CH₃) bimane solubilities were increased in the presence of β-CD. the formation of β-cyclodextrin inclusion complexes is proposed as a possible interpretation of these observations.     

Triplet-triplet absorption and polarization spectra of some syn-dioxabimanes

The triplet-triplet (T-T) absorption and polarization, singlet-singlet (S-S) absorption, and fluorescence spectra of syn-(methyl, hydrogen), syn-(tetramethylene), syn-(methyl, chloro)bimane, as well as those of syn-(phenyl, chloro), syn-(methyl, phenyl), and syn-(benzo)bimane were measured as part of a study of the factors that presumably control the laser action properties of the syn-bimanes.The syn-bimanes exhibit T-T absorption in the violet-blue/green portion of the spectrum and show two differently polarized transitions. A red shift in the S-S and T-T transition bands for a phenylbimane is dependent on the position of substitution (R₁ or R₂) and on the polarization of the bands. As substitution (R₁) along the long axis reduces T-T absorption over the fluorescence spectral region there is an improvement in laser action properties.Photoselection spectroscopy is briefly reviewed. Spectral arrangements and their polarizations (lasing constellations) of low-energy electronic transitions (S-S, T-T and fluorescence) that yield low T-T absorption within the fluorescence (laser action) spectral region and their correlation with molecular structure substituent effects are discussed.anti-Bimanes are proposed as possible phosphorescence laser materials.     

Single crystal X-ray diffraction analysis of 2,3a,4,5-tetrahydro-7,8-dimethoxy-3a-methyl-3H-benz[g]indazol-3-one hemihydrate

The structure of 2,3a,4,5-tetrahydro-7,8-dimethoxy-3a-methyl-3H-benz[g]indazol-3-one hemihydrate was unequivocally established by means of an X-ray diffraction analysis of a single crystal. The molecule crystallizes in the space group C2/c with unit cell parameters of a = 18.839(4), b = 7.7694(7), c = 18.211(2) Å and β = 101.06(1). The structure was solved by direct methods and refined by least-squares methods to an R-value of 0.069 for 2689 reflections. The indazol-3-one unit of the molecule is non-planar.     

Syntheses of 4-(benzo[b]furan-2 or 3-yl)- and 4-(benzo[b]-thiophen-3-yl)piperidines with 5-HT2 antagonist activity

The syntheses of 4-(benzo[b]furan-3-yl)piperidines, 4-(benzo[b]furan-2-yl)piperidines and 4-(benzo[b]thiophen-3-yl)piperidines with 5-HT₂ antagonist activity are described. Reaction of 1-acetyl-4-(2,4-difluorobenzo-yl)piperidine 2 with methyl glycolate gave methyl 6-fluoro-3-(1-acetylpiperidin-4-yl)benzo[b]furan-2-carboxylate 3 , which was converted to 2-[2-[4-(benzo[b]furan-3-yi)piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyridin-3(2H)-one hydrochloride 9 . Analogous benzo[b]furans 17a-d and benzo[b]thiophenes 10a,b and 18a were prepared by a similar method. Cyclization of 4-fluoro-2-(4-pyridinylmethoxy)acetophenones 20a,b afforded 4-(benzo[b]furan-2-yl)pyridines 21a,b , which were converted to 2-[2-[4-(benzo[b]furan-2-yl)-piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one hydrochlorides 24a,b. Among them, benzo[b]furans 9 and 17a,d and benzo[b]thiophenes 10 and 18a showed potent 5-HT₂ antagonist activity in vitro.     

A study of the spectra and acidity of 4,5-dihydro-1H-benz[g]indazol-7-ol and 2,3a,4,5-tetrahydro-7-hydroxy-3a-methyl-3H-benz[g]indazol-3-one

The synthesis of 2,3a,4,5-tetrahydro-7-hydroxy-3H-benz[g]indazol-3-one is recorded for the first time. Infrared, pmr, and uv spectral analysis of this pyrazolone and of 4,5-dihydro-1H-benz[g]indazol-7-ol strongly support the presence of one tautomer in each case. Measurements of pK_a values are in agreement with the proposed tautomeric structures based upon comparisons with simpler model systems. The data are taken in aqueous solution since the compounds are soluble at 10^?5 M and the results may more closely approximate that for the structure under physiological conditions.     

Bimanes. 19. Characteristics of the molecular structures of 1,5-diazabicyclo[3.3.0]octadienediones (9,10-dioxabimanes) determined by x-ray crystallography

The molecular structures of a variety of 1, 5-diazabicyclo[3.3.0]octadienediones (9, 10-dioxabimanes), including three 9, 10-dioxa-syn-bimanes, three 4, 6-bridged 9, 10-dioxa-syn-bimanes, and three 9, 10-dioxa-anti-bimanes, as determined by x-ray crystallography, are analyzed and compared with respect to planarity, bond distances, bond angles and intermolecular packing. “Planarity” may be the resultant of two non-planar equilibrium forms, a conclusion based on the anisotropic thermal motion parameters of the central N-N bond. “Amide”-type conjugation (N-C=O) is important in all planar bimanes; peripheral conjugation (N-C=C-C = O) is more significant in planar syn-bimanes and decreased conjugation is evident in the bent bridged syn-bimanes. Weak C? H…O bonds contribute significantly to the crystal packing arrangements.     

On the regioselectivity of the Friedländer reaction leading to huprines: stereospecific acid-promoted isomerization of syn-huprines to their anti-regioisomers

Racemic 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives (syn-huprines) substituted at the 9-position with a methyl or ethyl group, and both enantioenriched forms of the 9-ethyl derivative, obtained by chiral MPLC resolution of the racemic mixture, were readily converted to the corresponding anti-isomers (huprines) by stereospecific acid-promoted (AlCl₃ or triflic acid) isomerization of the endocyclic CC double bond from the 9(10)- to the 8(9)-position. These results support the hypothesis that the hitherto unseen syn-huprines are also formed under the usual acidic Friedländer reaction conditions used to prepare the known huprines, but rearrange in situ to the more stable anti-regioisomers (B3LYP/6-31G*).     

Beckmann Fragmentation and Rearrangement. Part VI thian-3-one oximes. Fragmentation reactions no. 26

In 70% aqueous dioxane thian-3-one anti-oxime p-toluenesulfonate (tosylate) ( 8b ) undergoes concerted fragmentation to the methylidenesulfonium ion 14 , part of which recyclizes to 1,3-thiazepin-4-one ( 11 ). With the syn-isomer 8b rearrangement to 1,4-thiazepin-3-one ( 10 ) and fragmentation to 14 occur in the ratio 4:1. Analysis of the rate data in 80% ethanol shows that anti fragmentation is 142 times as fast as syn fragmentation, but only 26 times as fast as rearrangement of the ‘homomorphous’ thian-4-one oxime tosylate ( 18b ). A comparison of the rates of cyclohexanone oxime tosylate 20 , thian-3- and -4-one oxime tosylates reveals the rate retarding influence of sulfur. – The configurations assigned to the stereoisomeric thian-3-one oximes ( 8a ) in the literature have to be reversed in the light of present results.     

Syntheses of some indazoles structurally related to equilenin

This study reports the complete synthesis and characterization of the 15, 16-diazaequilenin derivative 10,11-dihydro-3H-naphth[1,2-g]indazol-7-ol ( 2b ) as well as the methyl ether 2a of the above compound and the novel “model” compound 4,5-dihydro-1H-benz[g]indazol-7-ol ( 3b ). Indazoles 2a and 3a have demonstrated in vitro activity against a variety of microorganisms.     

Synthesis of (r)- and (s)-1-formyl-6,7,8,9-tetrahydro- N,N-(dipropyl)-3H-benz[e]indol-8-amines: Potent and orally active 5-ht1a receptor agonists

An efficient synthesis of the potent and orally active 5-HT_1A agonists, (R)-(+)- and (S)-(-)-1-formyl-6,7,8,9-tetrahydro-N,N-dipropyl-3H-benz[e]indol-8-amines 1a and 1b , is described. This synthesis was accomplished in twelve steps from commercially available 1,5,6,7-tetrahydro-4H-indol-4-one ( 5 ). The key step involved a regio-controlled Friedel-Crafts acylation of 1-(p-toluenesulfonyl)indol-4-acetyl chloride with ethylene to yield a versatile synthon, 3-(p-toluenesulfonyl)-6,7,8,9-tetrahydro-3H-benz[e]indol-8-one ( 10 ). Subsequent coupling of this ketone with chiral α-methylbenzylamine under reductive amination conditions yielded a mixture of diastereomers. These diastereomers were efficiently separated by either chromatography or fractional recrystallization of the derived hydrochloride salts. Debenzylation of the pure diastereomers was followed by alkylation and formylation to yield (R)-(+)- and (S)-(-)-enantiomers 1a and 1b with >99% purity.     

Methyl 2-benzoylamino-3-dimethylamonopropenoate in the synthesis of heterocyclic systems. A simple synthesis of amino derivatives of isomeric naphthopyranones and naphthodipyranones

A simple synthesis of the amino derivatives of 3H-naphtho[2,1-b]pyran-3-one 5b-d, 8,11 , and 20 , 2H-naphtho[1,2-b]pyran-2-one 14 and 19 , 2H,6H-naphtho[1,2-b:3,4-b']dipyran-2,6-dione 9 , 2H,11H-naphtho[2,1-b:3,4-b']dipyran-2,11-dione 12 , and 3H,9H-naphtho[1,2-b:5,6-b']dipyran-3,9-dione 15 from the corresponding monohydroxynaphthalenes 2c,d , dihydroxynaphthalenes 2b, 7, 10 , and 13 , and tetralones 16 and 17 with methyl 2-benzoylamino-3-dimethylaminopropenoate (3) in acetic acid is described.     

The schmidt reaction on 3a,4,5,6-tetrahydrosuccinimido[3,4-b]-acenaphthen-10-one and its alkylated derivatives

The rearrangement of 3a,4,5,6-tetrahydrosuccinimido[3,4-b]acenaphthen-10-one and two methylated derivatives using Schmidt conditions is described. The ratio of the major product, 2,3,8,9-tetrahydro-3-oxo-1H-benz[de]isoquinoline-1,9a-(7H)dicarboximide, to the minor product, 2,3,6,7-tetrahydro-3-oxo-4H-benz[ij]-isoquinoline-4,4a-(5H)dicarboximide, under different acidic conditions is given. The ratios of analogous products from the methylated derivatives are similar under similar conditions.     

Transformations of isomeric naphthopyranones. The synthesis of substituted β-naphthyl-α,β-dehydro-α-amino acid derivatives

The opening of the pyranone ring in 2H-naphtho[1,2-b]pyran-2-one derivative (1) and 3H-naphtho[2,1-b]-pyran-3-one derivatives 8 and 20 with nucleophiles afforded 3-(naphthyl-1)- and 3-(naphthyl-2)propenoates (substituted β-naphthyl-α,β-dehydro-α-amino acid derivatives) 7, 13, 14, 15, 24 , and 35 .     

Synthesis of Benzofuro-and Benzothieno-Phenanthridones by Twofold Photochemical Dehydrocyclization Reaction

Four new N-(p-chlorophenyl) carboxamides 1–4 of 9-phenanthrene-, 5-naphtho[2, 1-b] furan-, and 5-naphtho-and 4-naphtho[2, 1-b] thiophenecarboxylic acids have been synthesized. All carboxanilides were exposed to UV oxidative irradiation in methanolic solution. In the case of 2 and 3 corresponding benzo[d]-furo[3, 2-f] phenanthridin-10 (9H)-one 5 and benzo [d]-thieno[3, 2-f] phenanthridin-10 (9H)-one 6 are isolated.     

Die Dienol-Benzol-Umlagerung von Allyldienolen: aromatische [1,2]-, [3,3]- und [3,4]-sigmatropische Umlagerungen

The dienol-benzene rearrangement of syn and anti-4-allyl-4-methylcyclohexa-2,5-dien-1-ol (syn and anti 15) occurs by formation of a benzonium ion intermediate in p-toluene-sulphonic acid in ether below 0° and leads to a mixture of 2-, 3- and 4-allyltoluenes in the ratio 54:10:36. By the introduction of ¹⁴C-, D- and methyl labelled dienols it is shown that only the allyl group migrates and that this rearrangement is an intramolecular, one-step process. The formation of 2-allyltoluene occurs with retention, whereas the 3- and 4-allyltoluenes are formed by inversion of the carbon skeleton of the migrating allyl group. These rearrangements can be therefore classified as suprafacial, aromatic sigmatropic reactions of the order [1,2], [3,3] and [3,4]. The transition state can be postulated as representing a positively charged complex consisting of interacting allyl and tolyl radicals. The interaction of the two parts is controlled by the symmetry of the highest occupied π-orbitals (ψ₃ for toluene and ψ₂ for the allyl group) in agreement with the Woodward-Hoffmann rules. The better “distribution” of the charge in the transition state of these reactions in comparison to the ground state is chiefly responsible for the CoPE-like [3,3] sigmatropic reaction occurring at low temperatures. In general, sigmatropic reactions in charged systems are faster. The rearrangement of syn and anti 2-allyl-2-methylcyclohexa-3,5-dien-1-ol (syn and anti 28) gives results similar to those obtained with the para-allyldienols. The thermal rearrangement of 15 and 28 gives 3-allyltoluene by a [3,3] sigmatropic Cope rearrangement followed by elimination of water.     

Synthesis of representative 10-aryl-, 10-aralkyl- and 10-heteraryl-9H-naphtho[1′,2′:4,5]thiazolo[3,2-b]- [1,2,4]triazin-9-ones as potential anti-HIV agents

To prepare the title compounds, cyclocondensation of 1-amino-2-iminonaphtho[1,2-d]thiazole ( 2 ) with some representative glyoxylic acid derivatives was investigated. Heating 2 with methyl phenylglyoxylate ( 3a ) in methanol afforded only the open chain intermediates 4a,b . However, when this reaction was performed in re-fluxing glacial acetic acid, the expected compound, 10-phenyl-9H-naphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]- triazin-9-one ( 5a ) was produced in 27% yield. Similar treatment of 2 with benzyl-, 2-furyl- and 2-thienylgly-oxylic acids 3b-d gave the corresponding 10-benzyl-, 10-(2-furyl)- and 10-(2-thienyl)-9H-naphtho[1′,2′:4,5]thi-azolo[3,2-b][1,2,4]triazin-9-ones 5b-d in 48–67% yields. As by-products, 9-benzoyl- and 9-(2-thenoyl)naphtho-[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazoles 6a,d were also isolated. Compound 5a was selected for in vitro anti-HIV evaluation but found to be inactive.     

Reactions of derivatives of anthranilic acid with 3-chloropropyl isocyanate

The urea 1 obtained from anthranilonitrile and 3-chloropropyl isocyanate is converted into 3-(3-chloropropyl)-2,4(1H,3H)quinazolinedione ( 4 ) when heated with hydrochloric acid, whereas it undergoes a double cyclization to form 2,3,4,7-tetrahydro-6H-pyrimido[1,2-c]quinazolin-6-one ( 3 ) upon heating, or treatment with ammonia. On the other hand, the urea 5 formed from methyl anthranilate and 3-chloropropyl isocyanate cyclizes in three different ways, when treated with ammonia, potassium bicarbonate, or concentrated sulfuric acid, to yield compound 4 , 3,4-dihydro-2H,6H-[1,3]oxazino[2,3-b]quinazolin-6-one ( 9 ), or 2-[(3-chloropropyl)amino]-4H-3,1-benzoxazin-4-one ( 6 ), respectively. Acid-catalyzed reactions of compound 9 with nucleophilic reagents proceed with opening of the oxazine ring and readily yield various 3-substituted 2,4(1H,3H)-quinazolinediones.     

Conformation and Crystal Structure of Dipyrrinones with Oxindole Components

 Pyrrole α-aldehydes (2-formyl-4,5-dimethyl-1H-pyrrole and 2-formyl-N-methylpyrrole) condense readily at C(3) of indolin-2-ones to give dipyrrinone analogs, such as (3Z)-[(4,5-dimethylpyrrol-2-yl)-methylidenyl]-indolin-2-one and (3E)-[(1-methylpyrrol-2-yl)-methylidenyl]-indolin-2-one. ¹H-NMR NOE analyses and X-ray crystallography confirm the syn-(Z) configuration for the former and the syn-(E) configuration for the latter. The former is stabilized by intramolecular hydrogen bonding. Molecular mechanics calculations of the latter indicate no energy difference between the syn and anti conformations.     

Chemoenzymatic synthesis of the C-13 side chain of paclitaxel (Taxol) and docetaxel (Taxotere)

Reduction of methyl 3-chloro-2-oxo-3-phenylpropanoate with various reducing agents gave syn- and anti-3-chloro-2-hydroxy-3-phenylpropanoates 3, which underwent an efficient lipase-catalyzed resolution. All four diastereomers were subsequently converted to N-benzoyl-(2R,3S)-3-phenylisoserine methyl ester, C-13 side chain analogues of paclitaxel (Taxol).     

Azabicyclo chemistry II. Synthesis of 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepines. B-norbenzomorphans

The syntheses of the B-norbenzomorphans, 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepine (1a) and its N-methyl derivative (Ib) were accomplished. Phenylsuccinic anhydride (III) was cyclized to 3-carboxy-1-indanone (IVa), which was converted by the Arndt-Eistert method to the homologous methyl indanone-3-acetate (V). One experiment in the synthesis of V led to the by-products 3-carboxamido-1-indanone (IVd) and 3-(N-methylcarboxamido)-1-indanone (IVe), identified by physical and chemical means. Methyl 1-aminoindan-3-acetate (VII) was prepared by catalytic reduction of methyl indanone-3-acetate oxime (VI). Hydrolysis of VII afforded 1-aminoindan-3-acetic acid (VIII), which was cyclized with dicyclohexylcarbodiimide to 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepin-3-one (IX). Reduction (lithium aluminum hydride) of IX gave amine Ia which was then methylated to Ib. The mass spectral fragmentation patterns of IX and Ia are discussed.