Search

Based on the monoamine oxidase (MAO) inhibition properties of aminoheterocycles with a carbonitrile group we have carried out a systematic exploration to discover new classes of carbonitriles endowed with dual MAO and AChE inhibitory activities, and Aβ anti-aggregating properties. Eighty-three nitrile-containing compounds, 13 of which are new, were synthesized and evaluated. in vitro screening revealed that 31, a new compound, presented the best lead for trifunctional inhibition against MAO A (0.34 μM), MAO B (0.26 μM), and AChE (52 μM), while 32 exhibited a lead for selective MAO A (0.12 μM) inhibition coupled to AChE (48 μM) inhibition. Computational analysis revealed that the malononitrile group can find an advantageous position with the aromatic cleft and FAD of MAO A or MAO B. However, the total binding energy can be handicapped by an internal penalty caused by twisting of the ligand molecule and subsequent disruption of the conjugation (32 in MAO B compared to the conjugated 31). Conjugation is also important for AChE as well as the hydrophilic character of malononitrile that allows this group to be in close contact with the aqueous environment as seen for 83. Although the effect of 31 and 32 against Aβ, was very weak, the effect of 63 and 65, and of the new compound 75, indicated that these compounds were able to disaggregate Aβ fibrils. The most effective was 63, a (phenylhydrazinylidene)propanedinitrile derivative that also inhibited MAO A (1.65 μM), making it a potential lead for Alzheimer's disease application., European Cooperation in Science and Technology, Grant/Award Numbers: STSM CM1103-29512, STSM D34-05989, STSMCM1103- 29510; Portuguese Foundation for Science and Technology, Grant/Award Number: FCT -Project PTDC/SAUNEU/ 64151/2006 (MCC); Slovak Research and Development Agency (MM); Slovak Research and Development Agency; Foundation for Science and Technology

The lack of polarity sensing fluorophores with OFF-ON features when increasing the environment polarity has limited the monitoring of biological processes that involve an increase in local hydrophilicity. In this work, replacement of a hydroxyl group by a dimethylamino group transformed solvatochromic ICT naphthalimide- and quinolimide-based fluorophores into reversed solvatochromic ones, with higher emission in polar than in apolar environments. Excited-state dynamics studies, TD-DFT calculations, X-ray and NMR support the existence of a folded conformation for the 2-(dimethylamino)ethyl chain upon the imide ring in apolar solvents, where the dimethylamino group would quench the fluorescence by a PET effect, while in polar solvents the chain has an extended conformation, where the PET is hindered. These PET fluorophores have given rise to H2O and pH sensors in organic solvents as well as to bright macrophage cytoplasm imaging probes.

Efficient enzymatic synthesis of lactosyl-oligofructosides (LFOS) with a degree of polymerization from 4 to 8 was achieved in the presence of sucrose:lactosucrose and sucrose:lactose mixtures by transfructosylation reaction. The main synthesized LFOS which consist of β-2,1-linked fructose to lactosucrose: β-d-galactopyranosyl-(1 → 4)-α-d-glucopyranosyl-[(1 → 2)-β-d-fructofuranosyl]n-(1 → 2)-β-d-fructofuranoside (where n refers to the number of transferred fructose moieties) was structurally characterized by nuclear magnetic resonance (NMR). The maximum formation of LFOS was 81% (in weight with respect to the initial amount of lactosucrose) and was obtained after 24 h of transfructosylation reaction based on sucrose:lactosucrose (250 g L− 1 each) catalyzed by an inulosucrase from Lactobacillus gasseri DSM 20604 (IS). The production of LFOS in the presence of sucrose:lactose mixtures required a previous high-yield lactosucrose synthesis step catalyzed by using a levansucrase from Bacillus subtilis CECT 39 (LS) before the inulosucrase-catalyzed reaction. This novel one-pot bi-enzymatic system led to the synthesis of about 22% LFOS in weight, with respect to the initial amount of lactose (250 g L− 1). The results revealed a high specificity for the substrate involved in the inulosucrase-catalyzed reaction given that, although lactosucrose (O-β-d-galactopyranosyl-(1 → 4)-O-α-d-glucopyranosyl-(1 → 2)-β-d-fructofuranoside) acted as a strong acceptor of β-2,1-linked fructose, lactose (β-d-galactopyranosyl-(1 → 4)-α-d-glucose) was found to be an extremely weak acceptor., This work has been financed by project AGL2011-27884 from the Ministerio de Ciencia e Innovación. M. Díez-Municio is supported by CSIC through JAE-Pre Programme co-funded by ESF. M. Herrero thanks MICINN for his “Ramón y Cajal” contract.

Stereochemical and steric control of the relative spatial arrangement of the chromophoric units in multichromophoric systems offers an interesting strategy for raising unusual and appealing light-induced emission states. To explore and exploit this strategy, a series of conformationally restricted boron–dipyrromethene (BODIPY) dimers were designed by using tartaric acid as a symmetrical connector between the boron atoms of the dyes. The variety of stereoisomeric forms available for this bis(hydroxy acid) allows the relative spatial orientation of the chromophoric units in the dimer to be modified, which thus opens the door to modulation of the photophysical and chiroptical properties of the new bichromophoric systems. Chromophore alkylation introduces an additional level of control through distance-dependent steric interactions between the BODIPY units in the dimer, which also modulates their relative spatial disposition and properties.

Nonafluorobutanesulfonyl azide is an advantageous alternative to triflyl azide for the efficient synthesis of sulfonyl azides from sulfonamides in terms of its higher reactivity, lower cost, and non-hazardous nature. The reagent has proven its utility in a novel synthesis of N,N′-disulfonylamidines from available sulfonamides by a copper-catalyzed two-step, one-pot sequential process with added terminal alkynes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The preparation of the first structurally well-defined Janus nanocube showing two chemically distinct opposed faces is described. The synthetic approach is based on a highly efficient and symmetrycontrolled CuAAC functionalization of an octa-azido cubic silsesquioxane with a conformationally constrained tetra-alkyne with an appropriate spatial orientation of the triple bonds., with two sets of orthogonally reactive functional groups. We gratefully acknowledge financial support by the Spanish Ministerio de Ciencia e Innovación (project MAT2010-20646- C04-03) and Ministerio de Economía y Competitividad (project MAT2014-51937-C3-1-P). We also acknowledge the Spanish Ministerio de Economía y Competitividad for a FPI contract to A. B., and CSIC for a JAEDOC contract to J. R. S. and a JAEPRE contract to M. E. P.-O., and for support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

We report herein the silver-catalyzed cycloisomerization of readily available N-(prop-2-yn-1-yl)pyridine-2-amines as a new and practical method for the synthesis of differently substituted 3-methylimidazo[1,2-a]pyridines. The isomerization reactions proceeded under mild reactions conditions to give good yields and excellent regioselectivity. A DFT-based mechanistic analysis is also reported.

The production of new bioactive oligosaccharides is currently garnering much attention for their potential use as functional ingredients. This work addresses the enzymatic synthesis and NMR structural characterization of 2-α-d-glucopyranosyl-lactose derived from sucrose:lactose and sucrose:cheese whey permeate mixtures by using a Leuconostoc mesenteroides B-512F dextransucrase. The effect of synthesis conditions, including concentration of substrates, molar ratio of donor/acceptor, enzyme concentration, reaction time, and temperature, on the formation of transfer products is evaluated. Results indicated that cheese whey permeate is a suitable material for the synthesis of 2-α-d-glucopyranosyl-lactose, giving rise to yields around 50% (in weight respect to the initial amount of lactose) under the optimum reaction conditions. According to its structure, this trisaccharide is an excellent candidate for a new prebiotic ingredient, due to the reported high resistance of α-(1→2) linkages to the digestive enzymes in humans and animals, as well as to its potential selective stimulation of beneficial bacteria in the large intestine mainly attributed to the two linked glucose units located at the reducing end that reflects the disaccharide kojibiose (2-α-d-glucopyranosyl-d-glucose). These findings could contribute to broadening the use of important agricultural raw materials, such as sucrose or cheese whey permeates, as renewable substrates for enzymatic synthesis of oligosaccharides of nutritional interest., This work has been financed by projects POII10-0178-4685 from Junta de Comunidades de Castilla-La Mancha and European regional development fund (ERDF) and projects AGL2011-27884 and Consolider Ingenio 2010 FUN-C-FOOD CSD2007-00063 both from Ministerio de Ciencia e Innovación. M.D.-M. thanks CSIC for a JAE predoctoral fellowship.

We report the photo-oxidation of some di-2-benzothiazolylmethane derivatives and discuss the structure of the isolated methanols and ketones.

A suitable solid-phase approach, based on Fmoc/tBu methodology and on the use of 2-chlorotrityl resin, allowed a rapid and efficient preparation of new GPE analogues. Most of the synthesized tripeptides displayed glutamate receptor binding affinity comparable to that of GPE, but only a few derivatives showed significant neuroprotective activity., This work has been supported by the Spanish Ministry of Education and Science (SAF 2003-07207-C02 and CT2004-5358), Comunidad de Madrid (GR/SAL/0850/ 2004), and UTE project FIMA. S.A.A.D.D. holds a predoctoral fellowship from the Ministry of Education for Associated Units to CSIC. D.C. thanks CSIC for a I3P Grant.

We have reinvestigated the reaction of α-pyranosides-2-uloses 13 , 14 , 19 and 24 with DAST and shown that the 1,2-difluorinated compounds 17 , 18 and 25 are produced by a ring-contraction reaction. The reaction of 18 with benzyl alcohol gives the tri-benzyl derivative 26 or compound 27 , depending on the reaction conditions. Treating 17 with 2-naphthol produced the spiranic compounds 29 – 31 . The reaction of 17 with bis(trimethylsilyl)uracil produced the mononucleoside 28 , which preserves the fluorine atom in the more substituted carbon.

Two novel diglycosylated steroidal alkaloids of 5Δ-pregnene nucleus, named obtusine-20(R)-O-[β-thevetopyranosyl-(1→4)-β-cymaropyranoside] and obtusolactam-20(R)-O-[β-thevetopyranosyl-(1→4)-β-cymaropyranoside], together with the known β-sitosteryl-3-O-β-glucopyranoside were isolated from the roots of Cryptolepis obtusa N. E. Br., We thank Mr. Daniel Zunguza of the Faculty of Bi- ology, Eduardo Mondlane University, Mozambique, for his kindly collaboration in plant collection; Mrs. J. Hawkes of the Intercollegiate NMR Service Unit, Department of Chemistry, King's College London; Mr. Peter Haycock of the NMR Service of Queen Mary and West®eld College, London and Mr. Mark Domin of the Mass Spectrometry Service of School of Pharmacy, London. We want also to acknowledge INVOTAN-Portugal for a Ph.D. grant (13/A/94/PO) to Alexandra Paulo.

The oxidative cyclization of (E,E)-2′-hydroxycinnamylideneacetophenones 1a–e, and (E, E)-2′-benzyloxy-6′-hydroxycinnamylideneacetophenones 1i–l with DMSO/iodine, gave (E)-2-styrylchromones 3a–e,i–l. However, in the case of (E, E)-γ-alkyl-2′-hydroxycinnamylideneacetophenones 1f–h, (E)- and (Z)-2-styrylchromones 3f–h and 4f–h were obtained. The stereochemistry of the (E,E)-cinnamylideneacetophenones 1 and (E)- and (Z)-2-styrylchromones 3 and 4 was established by NOE experiments. The induced daylight photooxidative cyclization of some (E)-2-styrylchromones 3a,f–h gave 12H-benzo[a]xanthene-12-ones 6a,f–h.

Although almost 200-years-old, several unknown aspects remain to be explored of colchicine, the unique available drug for acute flares of gout. In this article, we report density-functional theory (DFT) studies of geometry, energy, and NMR; 1H-, 13C-, and 15N-NMR chemical shifts and some spin-spin coupling constants, including the complete analysis of the saturated part (ring B); the assignment of both enantiomers by NMR using a chiral solvating agent; solid-state NMR experiments of the different forms of natural and racemic colchicine, and IR and vibrational circular dichroism (VCD) studies of these same forms. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

Nonafluorobutanesulfonyl azide is an advantageous alternative to triflyl azide for the efficient synthesis of sulfonyl azides from sulfonamides in terms of its higher reactivity, lower cost, and non-hazardous nature. The reagent has proven its utility in a novel synthesis of N,N′-disulfonylamidines from available sulfonamides by a copper-catalyzed two-step, one-pot sequential process with added terminal alkynes.

We report herein the silver-catalyzed cycloisomerization of readily available N-(prop-2-yn-1-yl)pyridine-2-amines as a new and practical method for the synthesis of differently substituted 3-methylimidazo[1,2-a]pyridines. The isomerization reactions proceeded under mild reactions conditions to give good yields and excellent regioselectivity. A DFT-based mechanistic analysis is also reported.

We gratefully acknowledge the DGICYT of Spain for financial support (Project No. 92/19) and Dr Jose G. de la Campa for help with the MM+ calculations.

Polyhedral oligosilsesquioxanes (POSS) have recently attracted attention as scaffolds for the synthesis of multivalent bioconjugates. The synthesis of glycosyl-octasilsesquioxanes (glyco-POSS) using a copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition approach is reported. The problems associated with the use of bases or aqueous media in their preparation are investigated and a comprehensive study of the multivalent interaction between the mannosyl-octasilsesquioxanes and a model lectin, concanavalin A (Con A), using an array of complementary biophysical techniques is presented. The possibility to modulate the half-life of POSS conjugates in aqueous solution and the low toxicity of their constituent monomeric organosilanes offers an advantage over other scaffolds in vivo, preventing bioaccumulation and saturation of complementary receptors (lectins). Despite the hydrolysis in water, the octamannosyl-POSS studied shows a 50-fold higher binding affinity to Con A than methyl α-D-mannopyranoside. These experiments suggest that the novel glyco-POSS are attractive compounds for in vivo applications that require multivalent display of glycans., The authors thank the Spanish Ministerio de Ciencia e Innovación (projects CTQ-2006-15515-C02-02/BQU, CTQ2009-14551-C02-02, MAT2010-20646-C04-03, SAF2010-15670, and CTQ2010-15848), the Comunidad de Madrid (project S2009/PPQ-1634 “AVANCAT”), the Junta de Andalucía, and the European Union (FEDER and FSE) for fi nancial support. The authors also thank Ministerio de Ciencia e Innovación for FPU predoctoral contracts to B.T. and A.M.-A., and C.S.I.C. for a JAEPREDOC contract to M.E.P.-O.

The nmr and X-ray diffraction data of the novel ring system furo[3,2-e]imidazo[1,2-c]pyrimidine are reported in this paper. The crystal and molecular structure of this compound (C9H7N3O2·1/2H2O) has been solved at room temperature. Crystals are monoclinic in a space group of P2/n with cell constants a = 9.982(8), b = 13.526(9) and c = 13.981(9) A, β = 107.44(5)°, V = 1800.9 A3, Z = 8, Dx = 1.462 Mg·m−3. The structure was solved by full matrix least square refinement giving a final R = 0.054 (Rw = 0.069) for 1263 reflections (I>3.0σ(I)). The compound is essentially planar, existing in two slightly structural different forms, A and B. These are held in pairs with symmetry related molecules by hydrogen bonds formed with two water molecules. Then the dimeric units are stacked parallel to the c axis to form the tridimensional packing.

Two novel diglycosylated steroidal alkaloids of 5D-pregnene nucleus, named obtusine-20(R)-O-[b-thevetopyranosyl-(1 44)-b-cymaropyranoside] and obtusolactam-20(R)-O-[b-thevetopyranosyl-(1 44)-b-cymaropyranoside], together with the known b-sitosteryl-3-O-b-glucopyranoside were isolated from the roots of Cryptolepis obtusa N. E. Br. # 2000 Elsevier Science Ltd. Allrights reserved. Keywords: Cryptolepis obtusa; Periplocaceae or Asclepiadaceae; Saponins; 5D-pregnene steroidal alkaloids 1. IntroductionThe genus Cryptolepis R. Br. includes about 20species distributed throughout the tropical regions ofAfrica, Madagascar, Asia, Australia and Papua NewGuinea. The genus is assigned either to the Periplocoi-deae subfamily of the Asclepiadaceae or to the newlycreated family Periplocaceae (Hutchinson & Dalziel,1963; Cronquist, 1981), a taxon poorly investigatedfrom the chemical point of view. Continuing our stu-dies on the chemistry and biological activity of Crypto-lepis species (Paulo, Pimentel, Viegas, Pires, Duarte C Paulo, Duarte & Gomes, 1994; Paulo,Gomes & Houghton, 1995; Paulo, Gomes, Duarte,Perrett & Houghton, 1997; Paulo, Gomes, Steele, War-hurst & Houghton, in press) the roots of Cryptolepisobtusa N. E. Br. were analysed for their major second-ary metabolites. The aqueous extracts of roots of C.obtusa are traditionally used in Mozambique as ananti-abortive remedy, vermifuge and to treat abdomi-nal pains (Mendes & Jansen, 1984). To our knowledge,no phytochemical work has been reported on the rootsof this species. We describe herein the isolation andstructural elucidation, on the basis of extensive high-field NMR studies, of two new diglycosylated steroidalalkaloids (1 and 2) with a novel 5D-pregnene skeleton.2. Results and discussionTLC using general spray reagents (Wagner, Bladt &Zgainski, 1984) of the chloroformic crude extract ofthe roots of C. obtusa revealed the presence of alka-loidal and non-alkaloidal saponins as major constitu-ents. The chloroformic extract was chromatographedon a silica gel column and the alkaloid fractionobtained was further fractionated and purified bysemi-preparative HPLC and prep. TLC to a•ord com-pounds 1 and 2.Compound 1 gave positive reaction with the Dra-gendor• spray reagent and for that reason it was sus-pected to be an alkaloid. The molecular formula ofC

We have reinvestigated the reaction of α-pyranosides-2-uloses 13 , 14 , 19 and 24 with DAST and shown that the 1,2-difluorinated compounds 17 , 18 and 25 are produced by a ring-contraction reaction. The reaction of 18 with benzyl alcohol gives the tri-benzyl derivative 26 or compound 27 , depending on the reaction conditions. Treating 17 with 2-naphthol produced the spiranic compounds 29 – 31 . The reaction of 17 with bis(trimethylsilyl)uracil produced the mononucleoside 28 , which preserves the fluorine atom in the more substituted carbon.

3,4,5-Triamino-2 H -l,2,6-thiadiazine 1,1-dioxide 1 undergoes intermolecular cyclization, under different reaction conditions, to give a novel tricyclic system which shows interesting chelating properties toward ammonium ion. A spectroscopic study of this new tricycle and a mechanistic study of the reaction using an 15N-labelled intermediate has been carried out.

Glucopyranosides of methyl-1,2,6-thiadiazin-3(2H)-one 1,1-dioxides have been synthesized and their rotational isomerism studied. Two of them exist, in solution, as mixtures of syn : anti rotamers, at room temperature. In the case of the diglucoside, the barriers to rotation about both glycosidic bonds have been calculated by dynamic 13C NMR.

The influence of several modifications on the GPE tripeptide structure upon the binding to GluRs and on their neuroprotective effects has been studied. The results indicated that the prevention of neuronal death showed by GPE and some analogues is not directly related to their affinity at glutamate receptors., This work has been supported by the Spanish Ministry of Education and Science (SAF 2003-07207-C02) and Comunidad de Madrid (GR/SAL/0850/2004), and UTE project FIMA. S.A.A.D.D. holds a predoctoral fellowship from the Ministry of Education for Associated Units to CSIC.

The spectral data of a new Delta(7,22) sterol, 24S-ethyl-5 alpha-cholesta-7,22E-dien-3 alpha-ol beta-galactopyranoside, isolated from the bulbs of Autonoe madeirensis, are reported, This research was carried out with financial support from FundaÇao para a Ciência e Tecnologia (FCT/POCTI/FEDER).

Abstract—The synthesis of four new series of acyclic heteroaromatic receptors is described. They are built by two flexible polyether chains functionalised at their end with pyridazinone or methylpyridazine rings and connected by pyridine or benzene units. Their ability as carriers of lipophilic and hydrophilic phenethylamines and metallic cations has been evaluated. Transport rates show that, in general, these compounds are much more efficient carriers of lipophilic amines than of dopamine and NaC,KC and Ca2C ions. Their transport selectivities towards phenethylamine and homoveratrylamine are discussed on the basis of their structural features. Molecular modelling studies suggest that interaction of the aromatic moiety of the guest with the pyridazinone rings via double p-stacking, or with the pyridine ring by single p-stacking, should be responsible of their enhanced efficacy and selectivity in the transport of lipophilic phenethylamines., The authors thank the Spanish Comision Interministerial de Ciencia y Tecnologı´ a for financial support given to this research work (SAF99-0063). We are also grateful to the contributions of the Centro de Resonancia Magne´tica Nuclear for determining the 1D NMR spectra and the Centro de Microana´lisis of the Univ. Complutense de Madrid for elemental analyses.

A series of GPE analogues, including modifications at the Pro and/or Glu residues, was prepared and evaluated for their NMDA binding and neuroprotective effects. Main results suggest that the pyrrolidine ring puckering of the Pro residue plays a key role in the biological responses, while the preference for cis or trans rotamers around the Gly-Pro peptide bond is not important., This work has been supported by the Spanish Ministry of Education and Science (SAF2003-07207-C02). S.A.A.D.D. holds a predoctoral fellowship from this Ministry for Associated Units to CSIC.

The interaction of the pyrazole-containing macrocyclic receptors 3,6,9,12,13,16,19,22,25,26- decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 1[L1], 13,26-dibenzyl-3,6,9,12,13,16,- 19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 2[L2], 3,9,12,13,16,22,- 25,26-octaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 3[L3], 6,19-dibenzyl-3,6,9,12,13,- 16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 4[L4], 6,19-diphenethyl- 3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 5[L5], and 6,19-dioctyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene 6[L6] with L-glutamate in aqueous solution has been studied by potentiometric techniques. The synthesis of receptors 3-6[L3-L6] is described for the first time. The potentiometric results show that 4[L4] containing benzyl groups in the central nitrogens of the polyamine side chains is the receptor displaying the larger interaction at pH 7.4 (Keff ) 2.04 104). The presence of phenethyl 5[L5] or octyl groups 6[L6] instead of benzyl groups 4[L4] in the central nitrogens of the chains produces a drastic decrease in the stability [Keff ) 3.51 102 (5), Keff ) 3.64 102 (6)]. The studies show the relevance of the central polyaminic nitrogen in the interaction with glutamate. 1[L1] and 2[L2] with secondary nitrogens in this position present significantly larger interactions than 3[L3], which lacks an amino group in the center of the chains. The NMR and modeling studies suggest the important contribution of hydrogen bonding and ð-cation interaction to adduct formation., This work is devoted to the memory of Prof. Manuel Lora-Tamayo. Financial support by the Spanish “Comisio´n Interministerial de Ciencia y Tecnologı´a” (CICYT, Proyects SAF-99-0063, and BQU2003-09215-CO3-01) is gratefully acknowledged.

We have purified and identified a new phenolic compound in brandies aged in wood. Spectral structural analysis by HPLC-DAD suggested that the unknown compound corresponded to a 3-methoxy-4-hydroxybenzoic ketone with an aliphatic chain containing hydroxyl groups. 1H NMR analysis confirmed its structure as 2,3-dihydroxy-1-guaiacylpropan-1-one. Concentration of this ketone in brandies is related to the genuine aging of these beverages in oak and, therefore, to their market value.

A new synthesis of (E)-2-styrylchromones has been developed in paralell with synthetic studies on several flavone derivatives.

The treatment in a sodium methoxide/methanol solution of α,β-unsaturated enones or aldehydes with propanedinitrile in a 1:2 molar ratio led to 2-aminobenzene-1,3-dicarbonitriles. These compounds afforded 4-amino-8-cyanoquinazolines by reaction with formamide or guanidine

The synthesis and n.m.r. spectra (1H and 13C) are reported for 24 p-cymeneruthenium complexes belonging to one of the following families: [Ru(MeC6H4Pri-p)(acac)X](3)–(9), [Ru(MeC6H4Pri-p)(acac)L]BF4(10)–(17), [Ru(MeC6H4Pri-p)ClL2]BF4(19)–(22), and [Ru(MeC6H4Pri-p)L3][BF4]2(23), [Ru(MeC6H4Pri-p)XL2]BF4(24), and [Ru(MeC6H4Pri-p)X2L](25), where X = Br, I, N3, pz, mpz, dmpz, or idz, and L = pyridine, PPh3, CNBut, P(OMe)3, Hpz (pyrazole), Hmpz (3-methylpyrazole), Hdmpz (3,5-dimethylpyrazole), and Hidz (indazole) for complexes (3)–(17), and only azoles (pyrazoles and indazole) for the remaining ones. Crystals of [Ru(MeC6H4Pri-p)(pz)(Hpz)2]BF4 are monoclinic, space group P21/c, with a= 9.882 6(2), b= 13.966 3(3), c= 31.690 2(15)A, β= 94.650(3)°, and Z= 8. The structure was determined by X-ray diffraction and refined to R= 0.045 (R′= 0.036). There are two crystallographic units, each having an intramolecular hydrogen bond between a pyrazole and a pyrazolate ring, and another between the other pyrazole ligand and the BF4 anion. The n.m.r. data (δ and J) of the azole complexes were carefully determined and are thoroughly discussed.

The natural abundance 15N NMR spectra of sulphamide, sixteen 1,2,6-thiadiazine and two 1,2,4,6-thiatriazine derivatives, phenylbutazone and antipyrine have been recorded for the first time. The influence of substituents on nitrogen chemical shifts and the effect of intercalation of SO2 and CO groups between two nitrogen atoms are discussed. Prototropic tautomerism was also studied. 13C NMR data for some of the 1,2,6-thiadiazine and thiatriazine derivatives are reported.

Pyrazino[2,3-c]-1,2,6-thiadiazine 2,2-dioxides 1, 2, and 3 have been glycosylated as their trimethylsilyl derivatives with 1-O-acetyl derivatives of ribose. 1 leads to mixtures of N-1 and N-8 monoribosides and N-1,4-N diribosides, the relative proportions depending on the reaction conditions used. However, in the case of 6,7-disubstituted pyrazinothiadiazines 2 and 3 only the N-1 monoribosides have been obtained. The structures of the newly synthesized compounds are discussed on the basis of UV, 1H NMR and 2D homonuclear NMR data. Glycosylierungen von Pyrazino[2,3-c]-1,2,6-thiadiazin-2,2-dioxiden zu Schwefeldioxid-Analogen von Pteridin-Nucleosiden Die Pyrazino[2,3-c]-1,2,6-thiadiazin-2,2-dioxide 1, 2 und 3 werden als Trimethylsilyl-Derivate mit 1-O-Acetylribose-Derivaten glycosyliert. 1 liefert ein Gemisch der N-1- und N-8-Monoriboside sowie das N-1,4-N-Diribosid, wobei die Produktverteilung von den Reaktionsbedingungen abhangt. Mit den 6,7-disubstituierten Pyrazino[2,3-c]-1,2,6-thiadiazinen 2 und 3 werden lediglich die N-1-Monoriboside gebildet. Die Strukturen der neu synthetisierten Verbindungen werden auf der Basis der UV-, 1H-NMR- und 2D-NMR-Spektren diskutiert und gesichert.

Glucosidations of 4-amino-8H-pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide and its 6,7-dimethyl- and 6,7-diphenyl derivatives via the “silylation method” are described. The reaction favors N-1 substitution and the tetra-O-acetylglucopyranosyl derivatives 5, 6, and 7 as well as the free nucleosides 8, 9, and 10 have been isolated and characterized by UV, 1H, and 2D-NMR spectroscopy. The latter compound exist at room temperature, as rotationally restricted “syn-anti” isomers, and the free energies of activation have been calculated. Untersuchung der Rotationsisomerie und Synthese von Pyrazino[2,3-c][1,2,6]thiadiazin-2,2-dioxid-Glucosiden Glucosidierungen des 4-Amino-8H-pyrazino[2,3-c][1,2,6]thiadiazin-2,2-dioxids und seiner 6,7-Dimethyl- und 6,7-Diphenyl-Derivate mit Hilfe der „Silyl-Methode” Werden beschrieben. Die Reaktion fuhrt bevorzugt zu N-1-Substitution. Die entsprechenden Tetra-O-acetylglucopyranosyl-Derivate 5, 6 und 7 sowie die freien Nucleoside 8, 9 und 10 wurden isoliert und durch UV-, 1H- und 2D-NMR-Spektroskopie charakterisiert. Die freien Nucleoside liegen bei Raumtemperatur als rotationsgehinderte „syn/anti”-Isomere vor. Die freien Energien der Aktivierung wurden berechnet.

The electronic parameters of a series of mono- and difluoro aromatic compounds have been calculated by the quantum semiempirical method PM3. From these calculations, a relationship has been established between the charge on the aromatic carbon ipso to the fluorine and the reactivity of these compounds with hard nucleophiles, such as phenolate ions, to give aromatic ethers. A good correlation can also be established between charge on C ipso and the 13 C and 19 F NMR chemical shifts, used previously to measure the reactivity of fluorine compounds in the above indicated reaction

The computer-assisted analysis data of t1H NMR spectra of peracetylated α-and β-1 3- and -1 4-linked D-gal-actopyranosyl-D-galactopyranoses and several tetraacetylatedO-methyl derivatives of D-galactopyranose are reported.

Tautomerism of 2,5-disubstituted (4), 4,5,6-substituted (5), and 5-substituted 2H-1,2,6-thiadiazin-3-one 1,1-dioxides (6) has been studied by u.v., 1H, 13C and natural-abundance 15N n.m.r. spectroscopies. The effect of solvent concentration, temperature, and the nature of the substituents on the KT variation has been investigated. Comparison between the tautomeric behaviour of 2H-1,2,6-thiadiazin-3-one derivatives and the related pyrazol-5-ones provides some conclusions about the role of aromaticity on the stability of the different tautomers.