Cyclisation of benzils

Treatment of several substituted benzils [3,3′- and 4,4′-dimethyl-; 2,2′-, 3,3′- and 4,4′-dichloro-; 3,3′-dibromo-; 4-(N,N-dimethylamino)-] with an excess of chlorosulfonic acid gave the corresponding 3-chloro-2-phenylbenzofuran disulfonyl dichlorides. Disubstitution was confirmed by microanalytical and spectral data for the corresponding bis(N,N-dimethylaminsulfonamides). The positions of electrophilic substitution were not confirmed with 3,3′-dimethyl-, 2,2′- and 3,3′-dichlorobenzils. With 4,4′-dichlorobenzil, a smaller amount of chlorosulfonic acid enabled the isolation of 3,6,4′-trichloro-2-phenylbenzofuran-5-sulfonyl chloride, which was identified by X-ray analysis of the N,N-dimethylsulfonamide. The cyclisation failed with 3,3′-dimethoxy-, and 3,3′- and 4,4′-dinitrobenzils. The results have been interpreted mechanistically.     

Separation of isomeric and nonisomeric monoribonucleotides by isocratic ion pair high performance liquid chromatography

A simple, isocratic, high performance liquid chromatographic procedure is described for the first time for the separation of nine monoribonucleotides using the ion-pairing technique. An aqueous mobile phase containing 100 mM KH₂PO₄ and 12.5 mM tetramethylammonium hydroxide as the solvophobic ion, pH 3.9, was used with a reverse phase RP-18 column. The nine monoribonucleotides studied were separated and eluted in the following order: cytidine-5′ -phosphate, uridine-5′ -phosphate, cytidine-3′ -phosphate, guanosine-5′ -phosphate, uridine-3′ -phosphate, uridine-2′ -phosphate, adenosine-5′ -phosphate, guanosine-3′ -phosphate, and adenosine-3′ -phosphate. Generally the 5′ nucleotides eluted faster than the 3′ and the order of elution within each series was: cytidine, uridine, guanosine, and adenosine. The only nucleotide where three isomers were studied was uridine, and the 2′ eluted later than the 3′. Baseline separation was attained for a mixture containing four 3′ nucleotides and uridine-2′ -phosphate. When the four 5′ nucleotides were chromatographed, baseline separation was also obtained except between cytidine-5′ -phosphate and uridine-5′ -phosphate. The coefficient of variation of the retention characteristics, which reflected day-to-day variation, averaged 6.4%.     

Design and synthesis of the 3′-aminocarbonylamino,aminothiocarbonylamino and N-(Hydroxy)guanidinyl derivatives of thymidine as potential anti-HIV agents

The 3′-substituted-3′-deoxythymidines 3a (urea), 3b (thiourea) and 3c [N-(hydroxy)guanidinyl)] were designed based on the known structure-activity correlations for the active anti-HIV agent, 3′-azido-3′-deoxythymidine (AZT). Hydrolysis of 3′-cyanamido-3′-deoxythymidine ( 2 ) with ammonium hydroxide in the presence of hydrogen peroxide afforded the 3′-urea analogue 3a , whereas reaction with hydrogen sulfide in methanol gave the 3′-thiourea derivative 3b. The 3′-[N-(hydroxy)guanidinyl] compound 3c was synthesized by reaction of the 3′-cyanamide 2 with hydroxylamine.     

Intramolecular Participation of Amino Groups in the Cleavage and Isomerization of Ribonucleoside 3′‐Phosphodiesters: The Role in Stabilization of the Phosphorane Intermediate

A dinucleoside‐3′,5′‐phosphodiester model, 5′‐amino‐4′‐aminomethyl‐5′‐deoxyuridylyl‐3′,5′‐thymidine, incorporating two aminomethyl functions in the 4′‐position of the 3′‐linked nucleoside has been prepared and its hydrolytic reactions studied over a wide pH range. The amino functions were found to accelerate the cleavage and isomerization of the phosphodiester linkage in both protonated and neutral form. When present in protonated form, the cleavage of the 3′,5′‐phosphodiester linkage and its isomerization to a 2′,5′‐linkage are pH‐independent and 50–80 times as fast as the corresponding reactions of uridylyl‐3′,5′‐uridine (3′,5′‐UpU). The cleavage of the resulting 2′,5′‐isomer is also accelerated, albeit less than with the 3′,5′‐isomer, whereas isomerization back to the 3′,5′‐diester is not enhanced. When the amino groups are deprotonated, the cleavage reactions of both isomers are again pH‐independent and up to 1000‐fold faster than the pH‐independent cleavage of UpU. Interestingly, the 2′‐ to 3′‐isomerization is now much faster than its reverse reaction. The mechanisms of these reactions are discussed. The rate accelerations are largely accounted for by electrostatic and hydrogen‐bonding interactions of the protonated amino groups with the phosphorane intermediate.     

Substituted 2,2′‐Bis(2‐oxidobenzylideneamino)‐4,4′‐dimethyl‐1,1′‐biphenyl Complexes of Zinc

The condensation reaction of 2,2′‐diamino‐4,4′‐dimethyl‐6,6'‐dibromo‐1,1′‐biphenyl with 2‐hydroxybenzaldehyde as well as 5‐methoxy‐, 4‐methoxy‐, and 3‐methoxy‐2‐hydroxybenzaldehyde yields 2,2′‐bis(salicylideneamino)‐4,4′‐dimethyl‐6,6′‐dibromo‐1,1′‐biphenyl ( 1a ) as well as the 5‐, 4‐, and 3‐methoxy‐substituted derivatives 1b , 1c , and 1d , respectively. Deprotonation of substituted 2,2′‐bis(salicylideneamino)‐4,4′‐dimethyl‐1,1′‐biphenyls with diethylzinc yields the corresponding substituted zinc 2,2′‐bis(2‐oxidobenzylideneamino)‐4,4′‐dimethyl‐1,1′‐biphenyls ( 2 ) or zinc 2,2′‐bis(2‐oxidobenzylideneamino)‐4,4′‐dimethyl‐6,6′‐dibromo‐1,1′‐biphenyls ( 3 ). Recrystallization from a mixture of CH₂Cl₂ and methanol can lead to the formation of methanol adducts. The methanol ligands can either bind as Lewis base to the central zinc atom or as Lewis acid via a weak O–H ··· O hydrogen bridge to a phenoxide moiety. Methanol‐free complexes precipitate as dimers with central Zn₂O₂ rings.     

Isomeric bismaleimides and polyaspartimides

A study was conducted of the effects of meta-para isomerism on the synthesis and properties of aromatic bismaleimides and polyaspartimides. Three isomers, 3,3′-, 3,4′-, and 4,4′-diaminodiphenylmethanes (methylenedianilines), were used to prepare three isomeric bismaleimides. The bismaleimides then were reacted with their respective isomeric diamines in m-cresol solution to give a series of isomeric polyaspartimides. The properties of each of the isomeric series were measured and compared. Strong flexible films were solvent cast from the two polyaspartimides derived from the 3,4′- and 4,4′-diamines and their respective bismaleimides. Tensile properties of the films from the 3,4′-diamine/3,4′-bismaleimide combination polyaspartimide were equivalent to those from the 4,4′-diamine-derived polymer. That finding, together with that polymer's lower softening temperature and the nonmutagenic nature of the 3,4′-diamine monomer, suggested a potential usefulness for 3,4′-diaminodiphenylmethane as a replacement for 4,4′-diaminodiphenylmethane in addition polyimides.     

Synthesis of unsymmetrical arylthiophenes and bithienyls via oxidative cyclization of 1,3-butadiene-1-thiols

Oxidative cyclization of 2-mercapto-5-aryl-2,4-pentadienoic acids with iodine produced the respective 5-aryl-2-thenoic acids. The method was also suitable for the synthesis of unsymmetrical substituted 2,2′-bithienyls, and 2,3′-bithienyls. The synthesis of 5-carboxy-2′-bromo-5′-phenyl-2,3′-bithienyl from benzal-acetone demonstrated that oxidative cyclization of 1,3-butadiene-1-thiols is a useful procedure for preparing 5′-aryl-2,3′-bithienyls from simple carbonyl compounds. Preferential ring bromination of 2-phenyl-4-methyl-thiophene with N-bromosuccinimide and a radical catalyst was also observed.     

Schmelzreaktionen mit Aluminiumchlorid. I. Mitteilung. Über Kondensationsreaktionen von 1-Aminoanthrachinon und 1 -Amino-anthrachinon-2-sulfonsäure in der Pyridin-Aluminiumchlorid-Schmelze

The condensation of 1-aminoanthraquinone to 1,1′-diamino-2,2′-dianthraquinonyl in a melt of anhydrous aluminium chloride and moist pyridine has been reinvestigated. By a similar procedure under anhydrous conditions the sodium salt of 1-aminoanthraquinone-2-sulfonic acid yielded the sodium salt of 4,4′-diamino-1,1′-dianthraquinonyl-3,3′-disulfonic acid.     

Nucleotides. Part XXXIVSynthesis of Modified Oligomeric 2′–5′A Analogues: Potential Antiviral Agents

A series of new 2′–5′-oligonucleotide trimers carrying a 9-(2′,3′-anhydro-β-D -ribofuranosyl)-( 59 ), 9-(3′-deoxy-β-D -glycero-pent-3-enofuranosyl)-( 63 ), 9-(3′-azido-3′-deoxy-β-D -xylofuranosyl)-( 62 ), and 9-(3′-halo-3′-deoxy-β-D -xylofuranosyl)adenine ( 60 and 61 ) moiety at the 2′-terminal end have been synthesized via the phosphotriester method. The properly protected, modified monomeric building blocks ( 6 , 9 , 16 , 19 , 27 , 33 , 36 , 37 , and 43 ) were obtained, in general, by a sequence of reactions, introducing the protecting groups into the right positions. Their condensations with the intermediary dimeric 2′-terminal phosphodiesters 48 and 49 led to the fully protected 2′–5′-trimers 50–58 which were deblocked to form the free 2′–5′-trimers 59 – 63 . Easy elimination of HBr on deprotection did not allow to form the trimeric (3′-bromo-3′-deoxy-β-D -xylofuranosyl)adenine analogue but only 63 carrying an unsaturated sugar moiety instead. The newly synthesized compounds have been characterized by UV and NMR spectra as well as by elemental analysis.     

Efficient Solid Phase Synthesis of Cleavable Oligodeoxynucleotides Based on a Novel Strategy for the Synthesis of 5′‐S‐(4,4′‐Dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside Phosphoramidites

The incorporation of a specific cleavage site into an oligodeoxynucleotide can be achieved by utilizing the four 5′‐S‐(4,4′‐dimethoxytrityl)‐2′‐deoxy‐5′‐thionucleoside 3′‐(2‐cyanoethyl diisopropylphosphoramidites) 5 and 15a – c (Fig. 1). Based on the silver ion assisted cleavage of P? S and C? S bonds, we synthesized oligodeoxynucleotides with an achiral 5′‐phosphorothioate linkage 3′–O–P–S–5′ by the solid‐phase phosphoramidite procedure. The efficient cleavage of these modified oligodeoxynucleotides can be detected by HPLC, PAGE, and surface plasmon resonance (SPR) spectrometry. The liberated 5′‐thiol moiety can be used directly for post‐reaction labeling with appropriately functionalized reporter groups.     

A synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine via a bromine rearrangement during fluorination with MOST reagent

A facile method for the synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine 6 has been developed. Fluorination of 5′-O-acetyl-3′-β-bromo-3′-deoxyadenosine 3 with MOST gave 2′-β-bromo-3′-α-fluoro-2′,3′-dideoxyadenosine 4 via a rearrangement of the 3′-β-bromine to the 2′-β position during 3′-α fluorination. The 2′-β bromine was reduced by radical reduction and then the 5′-O-acetyl group was removed to afford 3′-α-fluoro-2′,3′-dideoxyadenosine 6 in good yield. A possible mechanism for the rearrangement is discussed.     

Hydrogen bonding in phenols—XI : Intramolecular hydrogen bonds in 2-hydroxy-R′-diphenylmethanes

The ν(OH) bands of a series of 2-hydroxy-R′-diphenylmethanes (R′ = H, 4′-Me, 4′-Et, 4′-CH(Me₂), 4′-C(Me₃), 2′,4′,6′-three Me, 2′,3′,5′,6′-tetra Me and 2′,3′,4′,5′,6′-penta Me) have been studied over a range of temperatures. Enthalpies (ΔH°) and entropies (ΔS°) of interaction were estimated from the temperature dependencies of equilibrium constants. The positive values of ΔH° were found with compounds containing a Me group in ortho-positions suggesting that π-associated conformers are less favoured than the free conformers.     

Facile access to some new 3,3′-bipyrazole-ester derivatives utilizing bis-hydrazonoyl chlorides

The 1,3-dipolar cycloaddition reaction of bis-hydrazonoyl chlorides with ethyl propiolate and dimethyl acetylenedicarboxylate afforded diethyl 1,1′-aryl-3,3′-bipyrazole-4,4′-dicarboxylate and tetramethyl 1,1′-diaryl-3,3′-bipyrazole-4,4′,5,5′-tetracarboxylate esters, respectively. Heating the latter two compounds with a mixture of HCl/AcOH furnished the same product: 3,3′-bipyrazole-5,5′-dicarboxylic acid. Reaction of the tetracarboxylate ester with aniline derivatives and with hydrazine gave the corresponding bipyrazole-fused heterocycles. Heating the dicarboxylic acid with 2-aminothiazole gave the corresponding bis-amide derivative. The structures of the products were established by elemental analysis, spectral data, and single-crystal X-ray crystallography.     

Syntheses of helical polymers through the combination of axially dissymmetric segments

Wholly aromatic polymers with various helical structures were prepared through the combination of two axially dissymmetric bifunctional compounds. The palladium-catalyzed condensation of (R)-2,2-diethoxy-6,6′-dibromo-1,1′-binaphthyl with (R)-1,1′-binaphthyl-2,2′-diamine and the reaction of (S)-2,2-diethoxy-6,6′-dibromo-1,1′-binaphthyl with (S)-1,1′-binaphthyl-2,2′-diamine produced helical polyamines, and the chiral conformation was confirmed by their circular dichroism spectra and large specific rotations. The combination of (R)-2,2-diethoxy-6,6′-dibromo-1,1′-binaphthyl and (S)-1,1′-binaphthyl-2,2′-diamine afforded polyamines with a zigzag conformation. The condensation of (R)-2,2′-dimethylbiphenyl-6,6′-dicarbonyl chloride with (R)-2,2′-diamino-6,6′-dimethylbiphenyl and the reaction of (S)-2,2′-dimethylbiphenyl-6,6′-dicarbonyl chloride with (S)-2,2′-diamino-6,6′-dimethylbiphenyl predominantly yielded cyclic dimers and tetramers because of the steric proximity of the reactive groups of the propagating species. The experimental results indicated that the structures of the obtained polymers depended on the combination of the chirality of the bifunctional atropisomeric compounds and the position of the functional groups on the aromatic rings. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4607–4620, 2004     

Synthesis,Dynamic Combinatorial Chemistry,and PCR Amplification of 3′–5′ and 3′–6′ Disulfide‐linked Oligonucleotides

Disulfide dithymidines linked 3′–5′ or 3′–6′ were synthesized and incorporated into oligonucleotides through a combined phosphotriester and phosphoramidite solid‐phase oligonucleotide synthesis approach. The disulfide links are cleaved and formed reversibly in the presence of thiols and oligonucleotides. This link was shown to be sequence‐adaptive in response to given templates in the presence of mercaptoethanol. The artificial 3′–5′ and 3′–6′ disulfide link was tolerated by polymerases in the polymerase chain reaction (PCR). By using sequencing analysis, we show that single mutations frequently occurred randomly in the amplification products of the PCR.     

A systematic approach to the AA′BB′, AA′BB′MX and derived systems in nuclear magnetic resonance

The AA′BB′ and AA′BB′MX nuclear magnetic resonance spin systems for I = ½ nuclei have been analysed. Expressions for the transition frequencies and intensities have been obtained which have the maximum accuracy consistent with practicable use. The analyses have been applied respectively to a hypothetical AA′BB′ nuclear spin system and to the two molecules para- fluoro-phenyldichlorophosphine and tris-para-fluorophenylphosphine. Inconsistencies in earlier treatments of the AA′BB′ system have been clarified.     

Convenient Synthesis of Nucleoside‐5′‐Diphosphates from the Corresponding Ribonucleoside‐5′‐phosphoroimidazole

The reaction of ribonucleoside‐5′‐phosphoroimidazolide with a tributylammonium orthophosphate in anhydrous dimethylformamide at room temperature provides a general method for the synthesis of nucleoside‐5′‐diphosphates. The novelty of the approach is to use the triethylammonium salt of 5′‐monophosphate nucleoside derivative prior to the imidazolate reaction with imidazole, triphenylphosphine, and 2,2′‐dithiodipyridine. Deprotection, followed by displacement of the imidazole moiety using tributylammonium orthophosphate and a catalytic amount of zinc chloride in dimethylformamide gave the desired 5′‐diphosphate products. The triethyl ammonium salt of 5′‐diphosphate nucleosides was purified by flash chromatography using DEAE (diethylaminoethyl weak anion exchange resin) Sepharosa fast flow packed in an XK 50/60 column on an Akta FPLC (Fast Protein Liquid Chromatography). Synthesis procedures are reported for adenosine‐5′‐diphosphate, uridine‐5′‐diphosphate, cytidine‐5′‐diphosphate, and guanosine‐5′‐diphosphate. Yields for the displacement reactions ranged from 95 to 97%. Thus, this method offers the advantages of shorter reaction time, greater product yield, and a more cost‐effective synthetic route.     

Synthesis,Dynamic Combinatorial Chemistry,and PCR Amplification of 3′–5′ and 3′–6′ Disulfide‐linked Oligonucleotides

Disulfide dithymidines linked 3′–5′ or 3′–6′ were synthesized and incorporated into oligonucleotides through a combined phosphotriester and phosphoramidite solid‐phase oligonucleotide synthesis approach. The disulfide links are cleaved and formed reversibly in the presence of thiols and oligonucleotides. This link was shown to be sequence‐adaptive in response to given templates in the presence of mercaptoethanol. The artificial 3′–5′ and 3′–6′ disulfide link was tolerated by polymerases in the polymerase chain reaction (PCR). By using sequencing analysis, we show that single mutations frequently occurred randomly in the amplification products of the PCR.     

对位取代酚钾与10′10′-二烃基-9,9′-联二吖啶盐电荷转移光谱的研究

10,10′-二烃基-9, 9′-联二吖啶盐有很强的荧光, 在光学材料^[1]和重金属离子的分析^[2]中有重要的应用价值。     

Nucleotides. Part XXXI. Modified Oligomeric 2′–5′ A Analogues: Synthesis of 2′–5′ oligonucleotides with 9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenine and 9-(3′-amino-3′-deoxy-β-D-xylofuranosyl)adenine as modified nucleosides

A series of new 2′–5′ oligonucleotides carrying the 9-(3′-azido-3′deoxy-β-D-xylofuranosyl)adenine moiety as a building block has been synthesized via the phosphotriester method. The use of the 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) blocking groups for phosphate, amino, and hydroxy protection guaranteed straightforward syntheses in high yields and easy deblocking lo form the 2′–5′ trimers 21 , 22 , and 25 and the tetramer 23 . Catalytic reduction of the azido groups in [9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenine]2′-yl-[2′-(O^p-ammonio)→ 5′]-[9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenin]-2′-yl-[2′-(O^p-ammonio)→ 5′]-9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenine ( 21 ) led to the corresponding 9-(3′-amino-3′-deoxy-β-D-xylofuranosyl)-adenine 2′–5′ trimer 26 in which the two internucleotidic linkages are formally neutralized by intramolecular betaine formation.