Spirocyclization of 1-(o-aminophenyl)cycloalkanols and 1-(2′-amino-3′-pyridinyl)cycloalkanols

A one-step synthesis of spiro[cycloalkane-1,4′-2H-3′,1-benzoxazin]-2′-ones and spiro[cycloalkane-1,4′-1H-pyrido[2′,3′-d][1,3′]oxazin]-2′-ones, obtained in good yield from the corresponding 1-(o-aminophenyl) and 1-(2′-amino-3′-pyridinyl)cycloalkanols is described using ethyl carbonate in presence of n-butyllithium.     

Separation of (3R, 3′ R)-, (3R, 3′ S; meso)-, (3S, 3′ S)- Zeaxanthin, (3R, 3′ R, 6′ R)-, (3R, 3′ S, 6′ S)- and (3S, 3′ S, 6′ S)-Lutein via the dicarbamates of (S)-(+)-α-(1-naphthyl) ethyl isocyanate

A method is described for the qualitative and quantitative determination of configurational isomers of zeaxanthin (=3,3′ -dihydroxy-β, β -carotene) and lutein (=3,3′ -dihydroxy-α -cartotene). It is based on the reaction of these zeaxathin and lutein isomers with (S)-(+)-α-(1-naphthyl) ethyl isocyanate to afford diastereomeric dicarbamates, which are analyzed by HPLC.     

Reaction of ketenes with N,N-disubstituted 2-aminomethylenecycloalkanones. V. Synthesis of N,N-disubstituted 4′-aminospiro [1,3-dithiane-2,3′-(5′,6′-polymethylene-3′,4′-dihydro-α-pyrones)]

The reaction of 2-carbonyl-1,3-dithiane, a sulfene prepared in situ from 2-chloroearbonyl-1,3-dithiane and triethylamine, with N,N-disubstituted 2-aminomethylvnecycloalkanones gave the 1,4-cycloadducts, namely N,N-disubstituted 4′-aminospiro[1,3-dithiane-2,3′-(5′,6′-poly-methylene-3′,4′-dihydro-α-pyrones)].     

Diethylbis(2,2′‐bipyridine)iron/MAO. A Very Active and Stereospecific Catalyst for 1,3‐Diene Polymerization

Diethylbis(2,2′‐bipyridine)Fe/MAO is an extremely active catalyst for the polymerization of 1,3‐dienes. Polymers with a 1,2 or 3,4 structure are formed from butadiene, isoprene, (E)‐1,3‐pentadiene and 3‐methyl‐1,3‐pentadiene, while cis‐1,4 polymers are derived from 2,3‐dimethyl‐1,3‐butadiene. The 1,2 (3,4) polymers obtained at 25°C are amorphous, while those obtained below 0°C are crystalline, as was determined by means of X‐ray diffraction. Mechanistic implications of the results are briefly discussed.     

Synthesis of 1,2′,3,3′,5′,6′-hexahydro-3-phenylspiro[isobenzofuran-1,4′-thiopyrans] and 1,2′,3,3′,5′,6′-hexahydro-3-phenylspiro-[isobenzofuran-1,4′-pyrans]

The 1,2′,3,3′,5′,6′-hexahydro-3-phenylspiro[isobenzofuran-1,4′-thiopyran] ring system ( 2a ) has been prepared from o-bromobenzoic acid. The 1,2′,3,3′,5′,6′-hexahydro-3-phenylspiro[isobenzofuran-1,4′-pyran] ring system ( 3a ) has been prepared from 2-bromobenzhydrol methyl ether. Several 3-(dimethylaminoalkyl) derivatives of both 2a and 3a were prepared by lithiation followed by alkylation.     

Synthesis of 3,3′-biisoxazoles from cyanogen N,N′-dioxide and trimethylsilyl enol ethers via the corresponding 5,5′-bis(trimethylsilyloxy)-3,3′-Δ2-biisoxazolines

Regioselective 1,3-dipolar cycloaddition of Cyanogen N,N′-dioxide ( 2 ) to trimethylsilyl enol ethers 3a-d, 6 and 7 gave the corresponding 5,5′-bis(trimethylsilyloxy)-3,3′-Δ²-biisoxazolines which upon short heating with 10% hydrochloric acid afforded 3,3′-biisoxazoles 5a-d , 8 and 9. Only the intermediate 5,5′-bis(trimethylsilyloxy)-derivative 4a was isolated and studied. Reaction of 2 with vinyl methyl ketone ( 10 ) gave biisoxazoline 11 which by oxidation with γ-manganese dioxide gave biisoxazole 12.     

Oxidative trifluoroacetamidation of (1<Emphasis Type="Italic">E</Emphasis>,3<Emphasis Type="Italic">E</Emphasis>)-1,4-diphenylbuta-1,3-diene and 1,1,4,4-tetraphenylbuta-1,3-diene

Reactions of trifluoroacetamide with (1E,3E)-1,4-diphenylbuta-1,3-diene and 1,1,4,4-tetraphenylbuta-1,3-diene in the oxidative system t-BuOCl–NaI have been studied. The reaction with (1E,3E)-1,4-diphenylbuta-1,3-diene afforded three products, N,N′-(phenylmethylene)bis(trifluoroacetamide), 3-chloro-4-iodo- 2,5-diphenyl-1-(trifluoroacetyl)pyrrolidine, and trifluoro-N-[(3E)-2-hydroxy-1,4-diphenylbut-3-en-1-yl]acetamide, with a high overall yield. 1,1,4,4-Tetraphenylbuta-1,3-diene failed to react with trifluoroacetamide.     

Diels-alder reaction of (E)-4-(2-nitroethenyl)-1H-imidazoles and methyl (E)-3-(1-imidazol-4-yl)propenoates

Diels-Alder reaction of methyl (E)-3-(1H-imidazol-4-yl)propenoates 2, 3a-c and (E)4-(2-nitroethenyl)-1H-imidazoles 3d,e with 2,3-dimethyl-1,3-butadiene, cyclopentadiene, and cyclohexa-1,3-diene gave the corresponding cycloadducts 6–9 .     

Synthese neuer Heptafulvene,Röntgenstrukturanalyse von ‘8,8-(1′,4′-Dioxotetramethylen)heptafulven’(2-(Cyclohepta-2,4,6-trien-1-yliden)cyclopentan-1,3-dion)

Synthesis of New Heptafulvenes; X-Ray Analysis of ‘8,8-(1′,4′-Dioxotetramethylene)heptafulvene’ (2-(Cyclohepta-2,4,6-trien-1-ylidene)cyclopentane-1,3-dione) Experimental procedures for the synthesis of heptafulvene ( 3a ), 8,8-tetramethylene heptafulvene ( 3c ) and ‘8,8-(1′,4′-dioxotetramethylene) heptafulvene’ (2-(cyclohepta-2,4,6-trien-1-ylidene)-cyclopentane-1,3-dion; 3d ) are described. The most important sequences include a low-temperature reaction of tropylium salts with lithium or Grignard carbenoids (Scheme 1) to give 3a and 3b as well as hydride abstraction from substituted cycloheptatrienes followed by deprotonation to give 3c and 3d . Limitations of these sequences are discussed. Two other heptafulvenes 3h and 3i are available by silylation of heptafulvenolates according to well-known procedures. NMR-Spectroscopic evidence as well as an X-ray analysis of 3d are presented. Compound 3d is a relatively polar heptafulvene with a planarised seven-membered ring as well as a partly delocalized π system.     

Synthetic antibacterials. VIII. 7-(1′-alkylhydrazino)-1,8-naphthyridines and related compounds

Synthesis and in vitro antibacterial activity of 7-(1′-alkylhydrazino)-1,8-naphthyridines related to nalidixic acid were investigated. Namely, treatment of 7-alkylamino-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids 1a-d with sodium nitrite in the presence of hydrochloric acid gave the 1-ethyl-1,4-dihydro-7-(N-nitrosoalkylamino)-4-oxo-1,8-naphthyridine-3-carboxylic acids 2a-d , which upon reacting with zinc dust in acetic acid gave the 7-(1′-alkylhydrazino)-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacids 3a-d. The compound 3a was alternately obtained by the reaction of 7-chloro-1-ethyl-1,4-dihydro-4-oxo-1,8-naphth-yridine-3-carboxylic acid ( 4 ) with methylhydrazine. The reaction of 7-chloro-4-hydroxy-1,8-naphthyridine-3-carboxylic acid ( 5 ) with methylhydrazine gave the 4-hydroxy-7-(1′-methylhydrazino)-4-oxo-1,8-naphthyridine-3-carboxylic acid ( 6 ), which upon treatment with alkyl halides afforded the 1-alkyl-1,4-dihydro-7-(1′-methyl-hydrazino)-4-oxo-1,8-naphthyridines 3a and 3e-g. The reaction of the appropriate 3 with ketones gave the corresponding 7-(1′-methylalkylidenehydrazino)-1,8-naphthyridines 7a-c and 8a-b. Among the compounds prepared, certain 3 and 7 exhibited good activity against Gram-negative bacteria.     

Ind-N-alkylation of rutaecarpine and synthesis of two novel related heterocyclic ring systems: Indolo[1′,2′:3,4]pyrazo[1,2-α]quinazoline and indolo[1′,2′:3,4] [1,4] diazepino[ 1,2-α]quinazoline

The failure to obtain the N-(13)alkylrutaecarpines ( 1d,e,f ) by heating rutaecarpine ( 1a ) with neat alkyl halides at 120° is discussed in comparison with the facile reaction with methyl iodide. In contrast, with alkyl halide-potassium carbonate in acetone, the corresponding N-(13)alkyl-rutaeearpines ( 1d-l ) are obtained in good yield. By use of 1,3-diiodopropane and 1,2-dibromo-ethane, this reaction provides a facile route to 12a and 13 which are derivatives of the heretofore unknown indolo[1,2′:3,4]pyrazo[1,2-α]quinazoline and indolo[1,2 :3,4][1,4]diazepino[1,2-α]quinazoline ring systems.     

Synthesis of Dispiro[indole‐3,2′‐pyrrolidine‐3′,2″‐pyrrolizine]‐1″,2(1H)‐diones via Azomethine Ylide 1,3‐Dipolar Cycloaddition

The 1,3‐dipolar cycloaddition of azomethine ylide generated in situ from isatin and sarcosine to 2‐arylmethylidene‐2,3‐dihydro‐1H‐pyrrolizin‐1‐ones afforded novel 1′‐methyl‐4′‐(aryl)‐1″H‐dispiro[indole‐3,2′‐pyrrolidine‐3′,2″‐pyrrolizine]‐1″,2(1H)‐diones in good yields. The structures of all the products were characterized thoroughly by NMR, infrared spectroscopy, mass spectrum, and elemental analysis.     

An Efficient Synthesis of 1′,7′,8′,9′‐Tetrahydrospiro[indoline‐3,4′‐pyrazolo[3,4‐b]quinoline]‐2,5′(6′H)‐dione Derivatives in Aqueous Medium

An efficient and green reactions of isatins, 3‐amine‐1H‐pyrazole (5‐methyl‐1H‐pyrazol‐3‐amine) and 1,3‐diketone in aqueous medium for the synthesis of novel 1′,7′,8′,9′‐tetrahydrospiro[indoline‐3,4′‐pyrazolo[3,4‐b]quinoline]‐2,5′(6′H)‐dione derivatives were reported in this research. The advantages of this reaction are simple operation, mild‐reaction conditions, wide scope substrate, high yields, and friendly environment. The products were confirmed by IR, ¹H NMR, ¹³C NMR, and HRMS.     

Acid-catalysed,nucleophile-catalysed and thermal decomposition of 2-amino-3-(2′,2′-dimethylaziridino)-1,4-naphthoquinone

The course of the thermal, acid-catalysed and iodide-catalysed decomposition of 2-amino-3-(2′,2′-dimethylaziridino)-1,4-naphthoquinone (III) was investigated. Thermal and iodide-catalysed decompositions gave mainly 2,3-diamino-1,4-naphthoquinone (VI) and 2-amino-3-(2′-methylallylamino)-1,4-naphthoquinone (V) together with low amounts of 2,2-dimethyl-1,2,3,4,5,10-hexahydrobenzo[g]quinoxaline (IV) and 2-isopropyl-1H-naphthoimid-azole-4,9-dione (VII). The acid catalysed isomerization of the aziridinonaphthoquinone III with halohydric acids or with acetic acid readily gave the opening of the aziridine ring; the corresponding salts of 2-amino-3-(2′-haloisobutylamino)-1,4-naphthoquinones (VIIIa-c) and 2-amino-3-(2′-acetoxyisobutylamino)-1,4-naphthoqunone (X) were formed by cleavage of the carbon-nitrogen bond at the substituted carbon atom. Hypotheses on the mechanism of these reactions are given.     

Synthesis of linear polyquaternary salts derived from 4,4′-Bipyridine

1,1″-(1,3-Propanediyl)bis-4,4′-bipyridinium dibromide is converted to 1,1″-(1,3-propanediyl)bis[1′-(3-hydroxypropyl)-4,4′-bipyridinium] tetrabromide by reaction with 1,3-dibromopropane in hot aqueous dimethylformamide. The tetraquaternary salt participates in a dequaternization and coupling reaction on treatment with hot aqueous hydrobromic acid to afford an octaquaternary salt, which is readily converted to decaquaternary and dodecaquaternary derivatives. The 1,4-butanediyl analogue participates in a similar sequence of reactions.     

3′-(1,2,3-Triazol-1-yl)-2′,3′-dideoxythymidine and 3′-(1,2,3-triazol-1-yl)-2′,3′-dideoxyuridine

Cycloaddition of different acetylenic compounds on the azido function of 3′-azido-2′,3′-dideoxythymidine and 3′-azido-2′,3′-dideoxyuridine afforded products with a 1,2,3-triazol-1-yl substituent in the 3′-position. In contrast with the parent compounds, these triazolyl derivatives had no appreciable activity against human immunodeficiency virus (HIV-1).     

Optically-active comb-branch liquid crystalline polymers having the chiral center in the flexible spacer unit. III. Copolymers of (S)-2-(4′-cyano-4-biphenylyloxy)-1-methylethoxy ethyl methacrylate and di[6-(4-methoxy-4′-oxybiphenyl) hexyl]-2-methylene butane-1,4-dioate

A new series of copolymers with optically-active liquid crystalline side chain units has been synthesized from the comonomers (S)-2-[2-(4′-cyano-4-biphenylyloxy-1-methylethoxy]ethyl methacrylate ( 1 ) and di[6-(4-methoxy-4′-oxybiphenyl)hexyl]-2-methylene butane-1,4-dioate ( 4 ). Chiral nematic phases were exhibited by two members of the series, rich in monomer 1 , while a smectic phase was exhibited in copolymers rich in 4 . While it was thought possible that ordered chiral liquid crystalline phases may be induced by copolymerizing chiral mesogenic monomers with mesogenic derivatives of itaconic acid where the high side chain density encourages greater ordering in the system, no evidence of smectic C^* phases could be found in the present systems. © 1993 John Wiley & Sons, Inc.     

Influence of 1,4‐dioxane solvent inclusion on the crystal structure of 5,5′‐diphenyl‐2,2′‐(p‐phenylene)di‐1,3‐oxazole (POPOP)

Crystallization of 5,5′‐diphenyl‐2,2′‐(p‐phenylene)di‐1,3‐oxazole (POPOP), C₂₄H₁₆N₂O₂, from chloroform or 1,4‐dioxane yielded crystals in pure and solvated forms, respectively. The solvated crystals of POPOP were found to contain 1,4‐dioxane in a strict 1:2 compound–solvent stoichiometry, C₂₄H₁₆N₂O₂·C₄H₈O₂, thus being a defined solvent‐inclusion compound. The crystal system is monoclinic in both cases and the asymmetric unit of the cell contains only half of the molecule (plus one dioxane molecule in the case of the solvated structure), owing to the centrosymmetry of the di‐1,3‐oxazole molecule.     

Synthesis and Properties of 2′-Deoxy-1′,2′-seco-D-ribosyl (5′ → 3′)oligonucleotides (= 1′,2′-seco-DNA) containing adenine and thymine

Some 2′-deoxy-1′,2′-seco-D-ribosyl (5′→3′)oligonucleotides (= 1′,2′-seco-DNA), differing from natural DNA only by a bond scission between the centers C(1′) and C(2′), were synthesized and studied in order to compare their structure properties and pairing behavior with those of corresponding natural DNA and homo-DNA oligonucleotides (2′,3′-dideoxy-β-D-glucopyranosyl oligonucleotides). Starting from (?)-D-tartaric acid, 2′-deoxy-1′,2′-secoadenosine derivative 9a and 1′,2′-secothymidine ( 9b ) were obtained in pure crystalline form. Using the phosphoramidite variant of the phosphite-triester method, a dinucleotide monophosphate 1′,2′-seco-d(T₂) was synthesized in solution, while oligonucleotides 1′,2′-seco-d[(AT)₆], 1′,2′-seco-d(A₁₀) and 1′,2′-seco-d(T₁₀) were prepared on solid phase with either automated or manual techniques. Results of UV- and CD-spectroscopic as well as gel-electrophoretic studies indicated that neither adenine-thymine base pairing (as observed in natural DNA and homo-DNA), nor the adenine-adenine base pairing (as observed in homo-DNA) was effective in 1′,2′-seco-DNA, Furthermore, hybrid pairing was observed neither between 1′.2′-seco-DNA and natural DNA nor between 1′,2′-seco-DNA and homo-DNA.     

Nucleoside und Nucleotide. Teil 16. Verhalten von 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)-pyrimidinon-5′-triphosphat, 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)pyridinon-5′-triphosphat und 4-Amino-1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)-pyridinon-5′-triphosphat gegenüber DNA-Polymerase

Nucleosides and Nucleotides. Part 16. The Behaviour of 1-(2′-Deoxy-β-D -ribofuranosyl)-2(1H)-pyrimidinone-5′-triphosphate, 1-(2′-Deoxy-β-D -ribofuranosyl-2(1H))-pyridinone-5′-triphosphate and 4-Amino-1-(2′-desoxy-β-D -ribofuranosyl)-2(1H)-pyridinone-5′-triphosphate towards DNA Polymerase The behaviour of nucleotide base analogs in the DNA synthesis in vitro was studied. The investigated nucleoside-5′-triphosphates 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyrimidinone-5′-triphosphate (pppM_d), 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone-5′-triphosphate (pppII_d) and 4-amino-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone-5′-triphosphate (pppZ_d) can be considered to be analogs of 2′-deoxy-cytidine-5′-triphosphate. However, their ability to undergo base pairing to the complementary guanine is decreased. When pppM_d, pppII_d or pppZ_d are substituted for pppC_d in the enzymatic synthesis of DNA by DNA polymerase no incorporation of these analogs is observed. They exhibit only a weak inhibition of the DNA synthesis. The mode of the inhibition is uncompetitive which shows that these nucleotide analogs cannot serve as substrates for the DNA polymerase.