Table of Contents

Abstract: n/a

Abstract: Sparteine N1-oxide and α-isosparteine N-oxide were prepared and theirstructures determined for the first time by ¹H- and ¹³C-NMR spectroscopy using twodimensionaltechniques. The N-oxide effects were also calculated.

Abstract: A series of novel N-benzylidenesulfonohydrazide compounds were designedand synthesized as inhibitors of UDP-N-acetylmuramic acid:L-alanine ligase (MurC) andUDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) from E. coli, involved inthe biosynthesis of bacterial cell-walls. Some compounds possessed inhibitory activityagainst both enzymes with IC₅₀ values as low as 30 μM. In addition, a new, one-potsynthesis of amidobenzaldehydes is reported.

Abstract: Two recently synthesized oxazolidinones: (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyloxazolidin-2-one (DA-7157) and itscorresponding pro-drug (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl) methyl disodium phosphate (DA-7218), have shown very goodactivity against several Gram positive bacteria, including Nocardia and Mycobacterium. Inthe present work we evaluated the therapeutic in vivo effects of DA-7218 on Nocardiabrasiliensis. We first determined the plasma concentration of the prodrug in BALB/c miceusing several doses and then tested its activity in an in vivo experimental actinomycetomamurine model. At the end of treatment, there was a statistically significant differencebetween the three drug receiving groups (25, 12.5 and 5 mg/kg) and the control group(saline solution) (p=0.001), proving that DA-7218 is effective for the treatment of experimental murine actinomycetoma. This compound could be a potential option forpatients affected with mycetoma by Nocardia brasiliensis.

Abstract: A new phenolic amide 8, together with the nine known phenolic compounds 1-7,9 and 10 were isolated from the MeOH extract of the roots of Paris verticillata. Thestructure of the new compound 8 was determined to be 1-N-feruloylaminobutyl-4-ρ-hydroxybenzamide by spectroscopic methods. The isolated compounds were tested forcytotoxicity against four human tumor cell lines using the SRB assay.

Abstract: Parkinson`s disease (PD) is a progressive, neurodegenerative disorder whichinvolves the loss of dopaminergic neurons of the substantia nigra pars compacta. Currenttherapy is essentially symptomatic, and L-Dopa (LD), the direct precursor of dopamine(DA), is the treatment of choice in more advanced stages of the disease. Substitutiontherapy with LD is, however, associated with a number of acute problems. The peripheralconversion of LD by amino acid decarboxylase (AADC) to DA is responsible for thetypical gastrointestinal (nausea, emesis) and cardiovascular (arrhythmia, hypotension) sideeffects. To minimize the conversion to DA outside the central nervous system (CNS) LD isusually given in combination with peripheral inhibitors of AADC (carbidopa andbenserazide). In spite of that, other central nervous side effects such as dyskinesia, on-offphenomenon and end-of-dose deterioration still remain. The main factors responsible forthe poor bioavailability and the wide range of inter- and intra-patient variations of plasmalevels are the drug’s physical-chemical properties: low water and lipid solubility, resultingin unfavourable partition, and the high susceptibility to chemical and enzymaticdegradation. In order to improve the bioavailability, the prodrug approach appeared to bethe most promising and some LD prodrugs have been prepared in an effort to solve theseproblems. We report here a review of progress in antiparkinson prodrugs, focusing onchemical structures mainly related to LD, DA and dopaminergic agonists.

Abstract: The aim of this study was to identify new compounds active againstPlasmodium falciparum based on our previous research carried out on 3-phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Twelve compounds weresynthesized and evaluated for antimalarial activity. Eight of them showed an IC₅₀ less than 1 μMagainst the 3D7 strain. Derivative 1 demonstrated high potency (IC₅₀= 0.63 μM) and goodselectivity (SI=10.35), thereby becoming a new lead-compound.

Abstract: The unexpected tendency of amines and functionalized hydrazines to reduceethyl 3-phenylquinoxaline-2-carboxylate 1,4-di-N-oxide (1) to afford a quinoxaline 1c andmono-oxide quinoxalines 1a and 1b is described. The experimental conditions werestandardized to the use of two equivalents of amine in ethanol under reflux for two hours,with the aim of studying the distinct reductive profiles of the amines and thechemoselectivity of the process. With the exception of hydrazine hydrate, which reducedcompound 1 to a 3-phenyl-2-quinoxalinecarbohydrazide derivative, the amines only actedas reducing agents.

Abstract: The unexpected substitution of fluorine atoms and phenoxy groups attached toquinoxaline or benzofuroxan rings is described. The synthesis of 2-benzyl- and 2-phenoxy-3-methylquinoxaline 1,4-di-N-oxide derivatives was based on the classical Beirut reaction.The tendency of fluorine atoms linked to quinoxaline or benzofuroxan rings to be replacedby a methoxy group when dissolved in an ammonia saturated solution of methanol wasclearly demonstrated. In addition, 2-phenoxyquinoxaline 1,4-di-N-oxide derivativesbecame 2-aminoquinoxaline 1,4-di-N-oxide derivatives in the presence of gaseousammonia.

Abstract: Two-, three- and four-arm, star-shaped poly(ε-caprolactone) andpoly(D,L-lactide) homopolymers, and copolymers of ε-caprolactone with D,L-lactide weresynthesized via ring-opening polymerization of cyclic esters in the presence of glycerol,penthaerythritol and poly(ethylene glycol) as initiators and stannous octoate as a catalyst.Thus obtained oligomers were successfully used in the synthesis of novel macromolecularprodrugs of norfloxacin. The structures of the polymers and prodrugs were elucidated bymeans of MALDI-TOF MS, NMR and IR studies.

Abstract: 3-Alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2a-g reacted with4-diethylaminobenzaldehyde to afford the corresponding 3-alkyl(aryl)-4-(4-diethylaminobenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3a-g. The acetylationreactions of compounds 3a-e were investigated and compounds 4a-e were thus obtained.The new compounds were characterized using IR, ¹H-NMR, ¹³C-NMR, UV and MSspectral data. In addition, the newly synthesized compounds 3a-g were titratedpotentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents suchas isopropyl alcohol, tert-butyl alcohol, acetone and N,N-dimethylformamide (DMF), andthe half-neutralization potential values and the corresponding pKa values were determinedfor all cases. Moreover, 3 and 4 type compounds were also screened for their antioxidantactivities.

Abstract: Using a bioactivity-guided fractionation method, two coumarins: minumicrolineacetonide (1) and epimurpaniculol senecioate (2), were isolated from the leaves ofMurraya omphalocarpa Hayata (Rutaceae). Compound 1 had been previously synthesizedand was now isolated from natural sources for the first time, and compound 2, possessing anegative optical rotation value, is new. The structures and their stereochemistry were fullyelucidated on the basis of spectroscopic and X-ray crystallographic techniques. Bothcompounds 1 and 2 are active in the antiplatelet aggregation assay. Interestingly, thepossible acetonide artifact 1 displayed significant antiplatelet aggregation induced not onlyby AA and collagen but also by platelet activating factor (PAF).

Abstract: Enantiopure chiral amidic derivatives of sinapic acid were oxidised withhydrogen peroxide using horseradish peroxidase (HRP) as the catalyst to give thearyltetraline dilignol thomasidioic acid. Trans-diastereoselectivity and enantioselectivity inthe formation of thomasidioic acid was observed. Computational methods show that theenantioselectivity is controlled by the β-β oxidative coupling step, while thediastereoselectivity is controlled by the stability of the reactive conformation of theintermediate quinomethide.

Abstract: Non-conventional techniques, such as microwave (MW) and power ultrasound(US) as well as combined MW/US irradiation, have been used to promote one-potsynthesis of second-generation ionic liquids (ILs), cutting down reaction times andimproving yields. However, the use of chloroalkanes in the alkylation of N-heterocyclesrequires more drastic conditions if results are to match those obtained with more reactivealkyl halides. The present paper describes a series of MW- or MW/US-promoted ILpreparations starting from chloroalkanes and classic heterocycles (1-methylimidazole,pyridine and 1-methylpyrrolidine). When reactions were carried out under conventionalheating in an oil bath they required longer reaction times and gave poorer yields. ¹H-NMRanalysis and ion-exchange chromatography showed that the present solventless procedureafforded ILs of satisfactory purity. The observed high yields (usually 70-98% isolated),and short reaction times showed that a straightforward access to ILs can be also achievedwith the use of alkyl chlorides, resulting in a considerable reduction of costs.

Abstract: Unsubstituted cyclic imides were synthesized from a series of cyclic anhydrides,hydroxylamine hydrochloride (NH2OH·HCl), and 4-N,N-dimethylamino-pyridine (DMAP,base catalyst) under microwave irradiation in monomode and multimode microwaves. Thisnovel microwave synthesis produced high yields of the unsubstituted cyclic imides forboth the monomode (61 - 81%) and multimode (84 - 97%) microwaves.

Abstract: The reaction of nitrilimine 6a with ethyl pyridine-2-acetate (7) gave thecorresponding pyrrolo[1,2-a]pyridine 8, while the reaction of 6b containing an estermoiety afforded the acyclic adduct 9. The reaction of 6a with 2-aminopyrimidine (10)gave the novel unexpected pyrimido[2,1-d]1,2,3,5-tetrazine 11. Acyclic adducts 16 and17 were obtained from the reaction of 6b with 2-cyanomethylbenzimidazole (14) and 2-aminobenzimidazole (15), respectively.

Abstract: In order to obtain new compounds with antitumoural action the N-(metaacylaminobenzoyl)-α-acylaminobenzoyl)-α-aminoacids 4-9 were prepared. Thesecompounds were subsequently converted into the corresponding δ²-oxazolin-5-ones 10-15,which in turn were submitted to a ring opening reaction with di-(β-chloroethyl)amine toafford the peptide supported N-mustards 16-21, which showed low toxicity and cytostaticactivity similar to that of sarcolisine against the Ehrlich ascite and Walker 253carcinosarcoma.

Abstract: Ground pearl (Eurhizococcus colombianus) is a crop pest in Colombia, withspecial impact on fig, grass, rubus and tomato plants. The insect is resistant to externalinsecticide application because it produces a thick waxy shell that isolates it from theenvironment. The composition of this shell was determined by NMR and MS as atriglyceride, whose fatty acid is transformed into other products with the metamorphosis ofthe insect. Additionally, several enzymatic inhibitors were assayed to control the insectwith negative results.

Abstract: Some novel Schiff bases have been prepared by reacting 6-azido-5-formyl-2-pyridone 1 with a series of aromatic amines 2a-f. 5-Arylaminomethylene-6-(E)-aryliminopyridones3a-e were obtained by reaction of 1 with 2a-e at room temperature,whereas with 2f, the 6-azido-5-naphthalen-2-yl-iminomethylpyridone derivative 4 wasformed. On the other hand, heating 1 with 2a-d at 140-150°C yielded two sets of isomericproducts, (E)-3a-d and (Z)-5a-d. Refluxing compounds (Z)-3a,c with hydroxyl-amine inmethanol gave the corresponding hydroxyliminopyridones 8a,c. Heating of (E)-3a-d withexcess POCl3 at reflux did not give the expected tricyclic compound 9, but rather theisomeric products (Z)-5a-d were obtained. The structures of all these products have beencharacterized using IR and 1H- and 13C-NMR spectroscopy.