Synthesis of Novel Imidazole-4,5-Dicarboxamide Derivatives

Imidazolecarboxamide derivatives have been known to exhibit biological activity, especially antiparasitic activity.¹ To date imidazole-4(5)-monocarboxamide derivatives and symmetrical imidazole-4,5-dicarboxamide derivatives have been investigated.¹ However, unsymmetrical imidazole-4,5-dicarboxamide derivatives, having different carboxamide groups, have not been investigated. Therefore, the author was prompted to devise a synthetic method for unsymmetrical diamide derivatives.     

Syntheses and characterization of a new class of mono‐ and heterodinuclear derivatives of boron derived from Schiff bases

Reactions of 2‐isopropoxy‐1, 3, 2‐ benzodioxaborole with equivalent amounts of Schiff base ligands having two hydroxyl groups ( 1a–3a ) yield mononuclear derivatives with one residual hydroxy group. The reactions of these mononuclear derivatives with hexamethyldisilazane in a 2:1 ratio yield heterodinuclear derivatives. All these newly synthesized derivatives have been characterized by elemental analyses and molecular weight measurements. Tentative structures have been proposed on the basis of IR and NMR (¹H, ¹³C, ¹¹B,²⁹Si)spectral data and Fab‐mass studies. Schiff bases and their corresponding mono‐ and heterodinuclear derivatives of boron have also been screened for antifungal activities. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and characterization of monomers and polymers of acrylated phosphonate esters derived from glycerol,D-mannitol,D-sorbitol,pentaerythritol, and dipentaerythritol

Phosphonic acid ester derivatives of glycerol, D -mannitol, D -sorbitol, pentaerythritol, and dipentaerythritol have been synthesized by transacetalation reactions with diethyl 2,2-diethoxyethylphosphonate. These phosphonated derivatives of polyols and carbohydrates have been esterified to from the corresponding methacrylates. All these compounds have been characterized on the basis of their elemental analysis and spectroscopic (infrared including FT–IR, ¹H-, ¹³C-, ³¹P-NMR, and mass) methods. Transacetalation reactions with dialkyl 2,2-dialkoxyethylphosphonate lead to the synthesis of 1,3-dioxane derivatives in the case of D -mannitol, pentaerythritol, and dipentaerythritol, whereas a mixture of both 1,3-dioxane and 1,3-dioxolane derivatives is obtained with D -sorbitol and glycerol. The methacrylates of phosphonylated polyol derivatives show the capacity to dissolve and interact with metal salts such as bismuth bromide and uranyl nitrate. Some of the polymers obtained from these monomers have been characterized on the basis of their spectral and thermal (differential scanning calorimetry) properties.     

Blocking-Deblocking of the NH-Functionality of Uracil and its Derivatives

We have been interested in various 5,6-dihydrouracils and 5,6-dihydroorotic acid derivatives as possible inhibitors of dihydrouracil dehydrogenase, dihydroorotase, and dihydroorotate dehydrogenase.² The known methods for the synthesis of 5,6-dihydrouracils and 5,6-dihydroorotic acid derivatives are either a low yield cyclization process³ or a catalytic hydrogenation⁴ procedure which frequently led to the elimination of desired functionality⁵. In order to obviate these difficulties, we have recently developed⁶ a mild non-catalytic method for the reduction of 5,6-double bond of uracil and orotic acid derivatives. By using lithium tri-sec-butyl borohydride^7–8 we have been able to reduce N₁, N₃-dialkyl uracil and orotic acid derivatives to the corresponding 5,6-dihydrouracil and orotic acid derivatives as shown in scheme (1).     

Nucleotide derivatives of biological importance. 8. Synthesis of adenosine triphosphate (ATP) analogs

Analogues of ATP belonging to the following classes have been prepared: N⁶-monoacyl derivatives, N⁶-mono- and -di-alkyl derivatives, 6-deamino-ATP, 8-bromo-ATP, 8-amino-ATP and ATP-N(1)-oxide. With the exception of the last compound, the corresponding AMP derivatives have been used as intermediates in these preparations.     

Generation and reactions of new ether and acetal functionalized tricyclo[3.3.0.0]oct-1(5)-ene derivatives. DSC and NMR studies on the [2+2] retrocycloaddition of several cyclobutane dimers

Two new highly pyramidalized tricyclo[3.3.0.0^3,7]oct-1(5)-ene derivatives containing ether and acetal functionalities have been generated, trapped as Diels-Alder adducts and dimerized. The initially obtained diene dimers were photochemically converted into cyclobutane derivatives. The thermal reversion of several cyclobutane derivatives to the corresponding dienes has been studied by ¹H NMR, ab initio calculations and DSC. For the first time, transannular additions of bromine and iodine to a diene dimer of this series have been observed.     

Structure elucidation,complete NMR assignment and PM5 theoretical studies of new hydroxy‐aminoalkyl‐α,β‐unsaturated derivatives of the macrolide antibiotic josamycin

Four new hydroxy‐aminoalkyl derivatives of α,β‐unsaturated macrolide‐josamycin (2–5) have been synthesised and their structures have been studied by means of ¹H and ¹³C NMR and FT‐IR methods. Complete assignment of resonances in the ¹H and ¹³C NMR spectra has been made on the basis of ¹H? ¹³C HSQC, ¹H? ¹³C HMBC, ¹H? ¹H COSY, ¹H? ¹H NOESY 2D experiments. Spectroscopic data indicated that for the derivatives 3 and 4 some equilibrium between two different structures exists in contrast to derivatives 2 and 5. The lowest‐energy structures of the new derivatives of josamycin have been calculated and visualised by PM5 method at semi‐empirical level of theory, taking into account the NMR and FT‐IR data. The most significant differences between the structures of josamycin and its newly synthesised derivatives' were found in the conformation of the macrolide aglycone part and in the mutual orientation of the 4‐O‐isovalerylmycarosylmycaminose moiety relative to the aglycone part. PM5 semi‐empirical calculations indicated that the structures of the new macrolide derivatives are stabilised by rather weak intramolecular hydrogen bonds in agreement with spectroscopic data. Antimicrobial properties of the new derivatives 2–5 as well as those having an acetate group at C‐3 (6 and 7) were determined and compared to that of the parent macrolide antibiotic josamycin (1). Copyright © 2010 John Wiley & Sons, Ltd.     

Analysis of fine splittings in the fourier transform 1H magnetic resonance spectra of some 15N labeled borazine derivatives

Proton NMR spectra are reported for ¹⁵N enriched borazine and a series of ¹⁵N enriched derivatives: N-methyl-borazine, N,N′-dimethylborazine and a new photochemical product, 1-methyl-2-aminoborazine. Chemical shifts for the ring (¹⁵N? H) protons have been measured. Using a Fourier transform spectrometer, fine structure in the ¹⁵N? H doublet is resolved. Ortho and meta ring proton and three-bond ¹⁵N to H coupling constants have been determined. Substituent effects on chemical shifts and coupling constants for borazine derivatives are compared with those for analogous benzene derivatives.     

Methylation of Thiouracils and Thioxanthines with Trimethyl Phosphate

Preparation of alkyl derivatives of thiouracils and thioxanthines has been carried out by ring cyclization¹ and sulfurization of alkyl derivatives of uracil and xanthines with phosphorus pentasulfide.^2–4 However, direct alkylation of thiouracils and thioxanthines has been described by a limited number of papers using dimethyl sulfate,^5,6 methyl iodide,^7,8 etc. Previously we reported that trimethyl phosphate (TMP) was useful for N-methylation of various azaaromatics.⁹ In view of the recent biological interest on methyl derivatives of natural products,¹⁰ we wish to communicate here the reactions of thiouracils and thioxanthines with TMP.     

Photocyclisation of 2-Methoxyphenyl Pheynil Ethers

The Photoinduced resotions of diaryl others have been extensively studied and are found to encompass rearrangesent to the 2- and 4-hydraxybiphanyl derivatives and other bond clesvage loading ultimately to the corresponding phenol and benzene derivatives.^2–6 On one occasion dibenzofuran was reparted as a photoproduct of diphenyl other⁷ but this observation has not been supported by latter work^4,8,9. In contrast 2-Ahlorophenyl 1-naphthyl other has been Shown to undergo efficient photodahydrohalogenstion to form benzo[b]naphtho[2,1-d]furan⁹.     

Design and Synthesis of p/m-[p-（un）Substituted Phenylsulfonamido]phenyl β-Diketo Acids and Quinoxalone Derivatives

Diketo acid derivatives are potent and selective HIV-1 integrase inhibitors. To investigate the detailed synthesis of those derivatives, a series of p/m-[p-（un）substituted phenylsulfonamido]phenyl β-diketo acid derivatives have been designed and synthesized. The quinoxalone derivatives as the potential bioisosteres of the biologically labile β-diketoacid pharmacophores have also been synthesized from reactions of the corresponding diketo acids with o-phenylenediamine. The structures of all diketo acid （ester） and quinoxalone derivatives were confirmed by 1^H NMR, 13^C NMR, IR, HRMS and/or MS （ESI）. X-ray crystallographic analysis of 11b demonstrates a similar arrangement of the side chain of quinoxalone derivatives with the parent diketoacids due to the intramolecular hydrogen bond （O…H-N） and the sp^2 hybridization configuration of the two nitrogen atoms of the quinoxalone ring.     

Synthesis and iNOS/nNOS inhibitory activities of new benzoylpyrazoline derivatives

A series of new Δ²-pyrazoline derivatives has been synthesized by means of a 1,3-dipolar-cycloaddition reaction. Ethyl 3-(5-methoxy-2-nitrobenzoyl)-Δ²-pyrazoline-5-carboxylate (5a) has been designed for the formation of the benzoylpyrazoline system present in these derivatives. Two synthetic routes have been utilized changing the starting products in the cycloaddition reaction. In both routes, the majority product obtained was only a Δ²-pyrazoline. The intermediate ethyl 1-acyl-3-(2-nitrobenzoyl-5-substituted)-Δ²-pyrazoline-5-carboxylate derivatives have been transformed into the final compounds by means of several chemical treatments. The compounds have been biologically evaluated as inhibitors of nitric oxide synthase (NOS), showing better affinity towards the inducible NOS isoform than versus neuronal NOS.     

Über Enolderivate der Chlorophyllreihe. Darstellung von 132,173-Cyclophäophorbid-enolen. Vorläufige Mitteilung

Enol derivatives in the chlorophyll series. Preparation of 13²,17³-cyclopheophorbide enols 13²,17³-Cyclopheophorbide enols have been prepared as model systems for studying the effect of ring E enolization upon the properties of chlorophyll derivatives.     

Conformational analysis of 3-borabicyclo[3.3.1]nonane derivatives

Conformations of 3-borabicyclo[3.3.1]nonane derivatives have been studied by means of ¹H and ¹³C NMR spectroscopy. With the aid of the coupling constants ³J(HH) and ¹³C chemical shifts it has been shown that all the derivatives of 3-borabicyclo[3.3.1]nonane with the trigonal boron atom studied are in a flattened double-chair conformation. In 3-borabicyclo[3.3.1]nonane derivatives with the tetra-coordinated boron atom and substituents at the 7α-position, the chair-boat conformation predominates, the boat conformation being characteristic of the cyclohexane ring; exceptions are the compounds with the internal donor—acceptor bond between the boron atom an 7α-substituent.     

Synthesis,Conformational Analysis and Extraction Studies of p-isopropylcalix[n]arene Derivatives (n = 4, 6, 8). A New Family of Molecular Receptors

Abstract

Ethers, esters and ketones, derivatives of p-isopropylcalix[n]arenes (n = 4,6,8), have been prepared; 33 new molecular receptors have been isolated and fully characterized. ¹H NMR and ¹³C NMR measurements reveal that tetraester and tetraketone derivatives are in cone conformation at room temperature when hexa and octa derivatives look like flexible flattened cones. Extraction studies with metal picrates from aqueous solution into dichloromethane were used to assess the ionophoric activity of the p- isopropylcalix[n]arene derivatives. The better E% are obtained with tetrameric derivatives in cone conformation, fully functionalized on the phenolic oxygens by ester or ketonic groups. The tetraamide derivative is the most efficient binder; the E% values are around 100 for Li, Na, K, Rb, Cs, Ca and Ba.     

Synthesis,Characterization, and DGAT1 Inhibition of New 5‐Piperazinethiazole and 5‐Piperidinethiazole Analogs

In this study, a novel series of 5‐piperazinethiazole 2,2‐dimethylbutanoic acid and 5‐piperidinethiazole 2,2‐dimethylbutanoic acid derivatives have been synthesized. Structures of the newly synthesized compounds have been elucidated using ¹H‐NMR, ¹³C‐NMR, high‐resolution mass spectroscopy, and high‐performance liquid chromatographic analysis. The synthesized derivatives have been evaluated in vitro for their ability to inhibit the enzyme diacylglycerol acyltransferase 1 responsible for triglyceride biosynthesis.     

Synthesis of 2,5-Dimethylpyrazine-3,6-Dicarboxylic Acid Derivatives

The general synthetic method of pyrazines¹ has been established. The method for synthesizing symmetrically substituted pyrazine derivatives, however, has not been well-studied.² Especially for synthesis of the title pyrazines, it is only described in a few words by Adkins³ and co-workers that ethyl 2-aminoacetoacetate employed in process to preparing of the threonine synthesis is spontaneously autoxidized to give 2,5-dimethyl-3,6-dicarbetoxy pyrazine as a byproduct. On the basis of this finding of Adkins, we have established a convenient method for the synthesis of 2,5-di-methylpyrazine-3,6-dicarboxylic acid derivatives (D_1–5) using the corresponding acetoacetic acid derivatives (A_1–4) as the starting materials (Scheme).     

13c-chemische verschiebungen und substituenteneffekte in methylazulenen

The ¹³C chemical shifts of all possible monomethyl azulenes and of some polymethyl derivatives have been determined by the Pulse Fourier Transform technique and have been assigned on the basis of ¹³C,H coupling constants and/or splitting patterns taken from proton coupled ¹³C NMR spectra. The shift differences observed in the monomethyl derivatives as compared to azulene itself are additive as far as sterically unperturbed polymethyl derivatives are concerned and can be viewed on as substituent constants. As is shown by the results of HMO- and EHT-calculations the substituent induced shifts in monomethyl azulenes without sterical hindrance can be correlated with charge density changes, with the exception of the β -effect, which is proportional to the bond length resp. the π bond order.     

17O NMR spectroscopy of transition metal carbonyls

NMR spectra of ¹⁷O in natural abundance have been obtained for a range of metal carbonyls. Linewidths of less than 10 Hz for the derivatives of Cr, Mo, W and Fe have been observed, although they are slightly larger for the derivatives of metals having an electric quadrupole moment. Comparison with the corresponding ¹³C NMR data shows that: (i) the chemical shift ranges are comparable, (ii) the ordering of chemical shifts is not very different, (iii) the linewidths are more favourable for ¹⁷O than ¹³C for some Mn and Co derivatives and allow an extension of the range of temperature in which information on the fluxional dynamics are obtainable in the rapid exchange limit.     

Spectral studies of the newly synthesized azomethine derivatives of zirconium(IV)

Equimolar and bimolar reactions of zirconium isopropoxide with bibasic tridentate azomethine (AZH₂) having the donor system ONO have been carried out and derivatives of the type Zr(OPr¹)₂(AZ) and Zr(AZ)₂ [Where AZ²⁻ is the anion of the azomethine molecule] have been isolated. The labile nature of the isopropoxy groups in 1∶1 derivatives has been shown by carrying out exchange reactions with equimolar amount of 2-methylpentane-2,4-diol. All the newly synthesized derivatives have been characterized on the basis of elemental analysis, conductance measurements, molecular weight determinations and infrared, ultraviolet, visible and proton magnetic resonance spectral studies.