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A chiral derivatizing agent (CDA) with the aldehyde function has been widely used in discriminating chiral amines because of the easy formation of imines under mild conditions. There is a preference for the use of cyclic aldehydes as a CDA since their lower conformational flexibility favors the differentiation of the diastereoisomeric derivatives. In this study, the imines obtained from the reaction between (S)-citronellal and the chiral amines (sec-butylamine, methylbenzylamine, and amphetamine) were analyzed by the nuclear Overhauser effect (NOE). Through NOE, it was possible to observe that the ends of the molecules were close, suggesting a quasi-folded conformation. This conformation was confirmed by theoretical calculations that indicated the London forces and the molecular orbitals as main justifications for this conformation. This conformational locking explains the good separation of 13C NMR signals between the diastereomeric imines obtained and, consequently, a good determination of the enantiomeric excess using the open chain (S)-citronellal as a CDA.

Made available in DSpace on 2019-10-06T16:21:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-06-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Leishmaniasis is a group of diseases caused by protozoan parasites from the genus Leishmania. There are estimated 1.3 million new cases annually with a mortality of 20,000–30,000 per year, when patients are left untreated. Current chemotherapeutic drugs available present high toxicity and low efficacy, the latter mainly due to the emergence of drug-resistant parasites, which makes discovery of novel, safe, and efficacious antileishmanial drugs mandatory. The present work reports the synthesis, characterization by ESI-MS, 1H and 13C NMR, and FTIR techniques as well as in vitro and in vivo evaluation of leishmanicidal activity of guanidines derivatives presenting lower toxicity. Among ten investigated compounds, all being guanidines containing a benzoyl, a benzyl, and a substituted phenyl moiety, LQOF-G2 (IC50-ama 5.6 μM; SI = 131.8) and LQOF-G7 (IC50-ama 7.1 μM; SI = 87.1) were the most active against L. amazonensis intracellular amastigote, showing low cytotoxicity to the host cells according to their selectivity index. The most promising compound, LQOF-G2, was further evaluated in an in vivo model and was able to decrease 60% of the parasite load in foot lesions at a dose of 0.25 mg/kg/day. Moreover, this guanidine derivative demonstrated reduced hepatotoxicity compared to other leishmanicidal compounds and did not show nephrotoxicity, as determined by the analyses of biomarkers of hepatic damage and renal function, which make this compound a potential new hit for therapy against leishmaniasis. Laboratório de Química Orgânica Fina Departamento de Química e Biologia Faculdade de Ciências e Tecnologia Universidade Estadual Paulista – UNESP, Campus de Presidente Prudente, Rua Roberto Simonsen, 305 Programa de Pós-Graduação em Ciência e Tecnologia de Materiais (POSMAT) Universidade Estadual Paulista – UNESP Departamento de Análises Clínicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista – UNESP Campus de Araraquara, Rodovia Araraquara-Jaú km1 Department of Pharmaceutical Chemistry Faculty of Life Sciences University of Vienna, Althanstraße 14 Laboratório ThoMSon de Espectrometria de Massas Instituto de Química Universidade de Campinas – UNICAMP Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo – USP, Avenida dos Bandeirantes, 3900 Department of Analytical Chemistry Faculty of Chemistry University of Vienna, Währinger Straße 38 Department of Neuroproteomics Paracelsus Medical University Laboratório de Química Orgânica Fina Departamento de Química e Biologia Faculdade de Ciências e Tecnologia Universidade Estadual Paulista – UNESP, Campus de Presidente Prudente, Rua Roberto Simonsen, 305 Programa de Pós-Graduação em Ciência e Tecnologia de Materiais (POSMAT) Universidade Estadual Paulista – UNESP Departamento de Análises Clínicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista – UNESP Campus de Araraquara, Rodovia Araraquara-Jaú km1 FAPESP: 2013/08248-1 FAPESP: 2013/24487-6 FAPESP: 2016/19289-9 FAPESP: 2017/03552-5

This Letter describes the use of NbCl5 as the Lewis acid in Friedel–Crafts reactions, in which a bifunctional electrophile reacts inter- and intramolecularly with an aromatic ring to produce a number of indanones in a single step, maintaining mild conditions and good yields.

A series of 3(2H)-furanones, based on side-chain modifications of a parent 3(2H)-furanone, was synthesized in good yield. The parent compound was prepared by hydrogenolysis, and subsequent acid hydrolysis, of isoxazole derivatives. The isoxazole was prepared by a [3+2] 1,3-dipolar cycloaddition reaction between 3-butyn-2-ol and nitrile oxide.

Theoretical methods were used for the correct structure assignments of the natural products jungianol and mutisianthol. A three stage protocol for the calculation was used: a conformational search using molecular mechanics (MM3), a DFT (B3LYP) structure optimization and ab initio (HF/GIAO) or DFT (B3LYP/GIAO) calculation of magnetic properties.

In this paper we describe the synthesis of a γ,δ-unsaturated aldehyde from a bicyclic Diels-Alder adduct, to be used in future electrocyclic reaction studies. A number of reactions produced undesired materials resulting from the interaction between functions, forcing the use of partial protection to accomplish a synthesis that would be otherwise straightforward. Suggestions to account for the results are given.

A set of amphiphilic p-menthan-3,9-diols have been investigated by molecular dynamics simulations. These are four stereoisomers than can be specifically obtained from two terpenoids widely used in biorganic chemistry. For this purpose, the p-menthan-3,9-diols have been explicitly parametrized using both semiempirical and ab initio quantum mechanical calculations. The reliability of these parameters has been validated by predicting different molecular and thermodynamic properties. Molecular dynamics simulations in aqueous solution have been performed with the new parameters. The results provide useful insights about the conformational properties of this family of compounds and the formation of intra- and intermolecular hydrogen bonds.

The conformational preferences of p-menthan-3,9-diols in both aqueous and chloroform solutions have been investigated by molecular dynamics simulations. The effects of changing the stereochemistry at the C3 atom on the dynamics of these compounds have been studied by considering the two epimers. The results reveal a strong dependence of conformation on both the stereochemistry and the environment. In some cases the formation of an intramolecular hydrogen bond stabilises unusual conformations for the cyclohexane ring.

Goyazensolide, a biologically active natural product classified as a furoheliangolide, was transformed in a phthalimide derivative that showed an enhanced biological activity against Tripanosoma cruzi. The complex natural product was also reduced with high stereoselectivity by hydrogen/Wilkinson’s catalyst, an epimer of this product was obtained in the reduction with hydrogen/Pd-C.

The core structure of the natural sesquiterpene lactones furanoheliangolides, an 11-oxabicyclo[6.2.1]undecane system, was synthesized through a pathway involving two Diels–Alder reactions.

A rationalization is suggested which can help organic chemists in realizing analyses of the relative stereochemistry of substituted cyclopentanes by proton NMR, through the coupling constants between vicinal hydrogens. Some useful generalizations, derived from the dihedral angles found for cyclopentane through a molecular mechanics program, are given.

Acetylenic esters, which are easily prepared by carbethoxylation of terminal acetylenes, can be hydrated regioselectively to β-keto-esters. In this paper, the terminal acetylenes were prepared by addition of lithium acetylide (complexed with ethylenediamine) to epoxides of cyclopentane derivatives to produce compounds oxygenated at the same position as certain natural products from Otoba parvifolia. The hydration was carried out by two different processes, producing either δ-oxygenated or γ,δ-unsaturated β-keto-esters.

A synthesis of a functionalized bicyclo[6.2.1]undecane, N -(7-hydroxymethyl-bicyclo[6.2.1]undeca-3,5,9-trien-2-yl)-4-methyl-benzenesulfonamide, is described. Starting with a [6+4] cycloaddition between cyclopentadiene and cycloheptatrienone, the final product was prepared in five steps with an overall 37% yield. The remarkable resistance to hydrolysis of an intermediate lactam was overcome by tosylating the amide and reducing with LiAlH 4 .

A method for the preparation of 3-substituted furans starting with the addition of bis(phenylthio)methyllithium to an ester, followed by a sequence consisting of a Wittig reaction, a DIBAL-H reduction and an iodine-mediated cyclization is described.

A simple and efficient method for the preparation of 1-methyl-3-oxo-7- oxabicyclo[2.2.1]hept-5-en-2-carboxylic acid methyl ester (1) is described. The first step is a highly regioselective Diels-Alder reaction between 2-methylfuran and methyl-3-bromo- propiolate. A remarkably difficult ketal hydrolysis reaction was effected by treatment with HCl, a simple reagent that was shown to be more efficient, in this case, than commonly used more elaborate methods.

Niobium pentachloride has proven to be a powerful activating agent for Diels-Alder or conjugate addition reactions of cycloenones. The Diels-Alder product was obtained only with an unsubstituted enone (cyclohexenone) and the highly reactive diene cyclopentadiene, substituents in the b-position of enones seem to prevent Diels-Alder reaction: oxygenated substituents favor the formation of vinyl chlorides (ethyl ether or dichloromethane as solvents) or enol ethers (ethyl acetate as solvent), while a methyl substituent prevents any kind of transformation with NbCl5. Less reactive dienes, furan and 2-methylfuran gave the conjugate addition products of the furan ring to the enone system.

A bicyclo[6.2.1]undecane model compound of the core structure of the biologically active furanoheliangolide sesquiterpene was synthesized. This new and short route was developed by using a solvent-free Diels–Alder reaction between cyclopentadiene and 3-nitro-2-cyclohexenone, followed by simple transformations. Theoretical calculations were performed in order to understand reactivity aspects of the cycloaddition.

The treatment of cerium metal with ethyl bromosuccinate ( 1 ) forms the stabilized organolanthanoid intermediate ( 2 ), which reacts with carbonyl compounds in a Reformatsky-type reaction, under mild conditions, to produce functionalized γ-substituted paraconic acids ( 4 ) in good yields.