Synthesis of novel sugar derived aziridines, as starting materials giving access to sugar amino acid derivatives

d-Erythrosyl aziridines were obtained from d-erythrosyl triazoles either by photolysis or through diazirine intermediates. These were found to undergo rich, high yielding chemistry by reaction with protic acids (HCl, BiI3/H2O and trifluoroacetic acid) leading to two types of furanoid sugar α-amino acids, and polyhydroxylprolines. Based on experimental evidence, reaction mechanisms have been proposed for the syntheses.We thank FCT for project funding PTDC/QEQ-MED/1671/2012; the NMR Portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho), and FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for fnancial support to CQ/UM. This study was funded by Fundação para a Ciência e a Tecnologia (SFRH/BD/87292/2012)

Intermolecular alkyl radical addition to methyl 2-(2,6-Dichlorophenyl)-2H-azirine-3-carboxylate

The 2H-azirine 1 acts as an effective radical acceptor for secondary and tertiary alkyl iodides mediated by triethylborane. The addition proceeds with high regio- and diastereo-selectivity

Intermolecular alkyl radical addition to methyl 2-(2,6-dichlorophenyl)-2H-azirine-3-carboxylate

The 2H-azirine 1 acts as an effective radical acceptor for secondary and tertiary alkyl iodides mediated by triethylborane. The addition proceeds with high regio- and diastereo-selectivity.The present work has been supported by Fundação para a Ciência e a Tecnologia, Ministério da Ciência e do Ensino Superior, projecto POCTI/32723/QUI/2000. Thanks are also expressed to Dr. T. L. Gilchrist for helpful discussions.info:eu-repo/semantics/publishedVersio

Synthesis of New Iminosugar Derivatives Based on (S)-(1,2,3,6-Tetrahydropyridazin-3-yl)methanol

(S)-(1,2,3,6-Tetrahydropyridazin-3-yl)methanol was synthesized in two steps by the Diels-Alder reaction of penta-2,4-dien-1-ol with diethyl azodicarboxylate in the presence of (S)-BINOL as chiral catalyst. The subsequent Boc-protection of the 2-position of the pyridazine ring, ring-closing carbonylation of the hydroxy group, and deprotection afforded a bicyclic iminosugar analog. The structure of the isolated compounds was proved by NMR, IR, and mass spectra and elemental analyses

Study based on electronic descriptors of the diastereoselective aza-diels-alder cycloaddition of [(1r)-10-(n,n-diethylsulfamoyl)isobornyl] 2h-azirine-3-carboxylate to e,e-1,4-diacetoxy-1,3-butadiene

Cycloaddition of chiral [(1R)-10-(N,N-diethylsulfamoyl)isobornyl] 2H-azirine-3-carboxylate to E,E-1,4-diacetoxy-1,3-butadiene shows complete diatereoselectivity giving a single cycloadduct (-)-(2S,5R,6R)-6-[(1R)-10-(N,N-diethylsulfamoyl)isobornyloxycarbonyl]-1-azabicyclo[4.1.0]hept-3-ene-2,5-diyldiacetate. Our main objective is to identify electronic/steric parameters capable of describing the observed tendencies of this reaction. The results of the calculations conclude that: even though the steric factors can play an important role at the initial steps of the reaction, at the transition states the behavior of several electronic parameters; like hardness, polarizability, aromaticity, charge transfer, etc is decisive enough to justify the obtained product. Finally, this work summarizes an exhaustive analysis of electronic descriptors and empirical reactivity principles, reaching a definitive and comprehensive explanation to the observed experimental result.Thanks to Fundação para a Ciência e Tecnologia (FCT) for partial financial support (project PTDC/QUI/67407/2006

Diastereoselective synthesis of analogues of neuraminic acid

Siliac acids frequently terminate oligosaccharide side chains in glycoproteins and glycolipids. In this position they have been found to mask recognition by proteases or glycosidases, extending glycoproteins and glycolipids lifetime and function.1 The interest in the sialic acids chemistry in which neuraminic acid is included has rapidly increased in last years, especially since their involvement in the regulation of a great variety of biological phenomena was recognised.2 In our previous work, we found that combination of D-erythrose 1,3-butadiene with t-butyl 2H-azirine 3-carboxylate through Diels-Alder cycloaddition gave as major product the (R)-configured cycloadduct 1, in 58% yield.3 Analogues of neuraminic acid can be achieved from this adduct in a few steps, following different methods of oxidation of the double bound (Scheme 1). Osmilation of the cycloadduct was found to be totally stereo-selective, the addition occurring by the si face. After benzylidene acetal cleavage under acid hydrolysis was obtained product 2. On the other hand, epoxidation of the cycloadduct followed by nucleophilicic ring-opening will give access to the configuration described in compounds 3, and by aziridination of the epoxide is achieved the L-gluco neuraminic acid configuration.We thank FCT for project funding PTDC/QEQ-MED/1671/2012; the NMR Portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho), and FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support to CQ/UM.info:eu-repo/semantics/publishedVersio

Synthesis and bioactivity of new analogue of Bicyclic 1-Azafagomine

New (S)-(1,2,3,6-tetrahydropyridazin-3-yl)methanol was synthesized by Lewis acid catalyzed and self-assembled Diels-Alder (LACASA-DA) cycloaddition reaction using (S)-BINOL as a chiral inductor. The N-2 pyridazine position was protected, the hydroxyl group was carbonylated to form the new bicyclic structure. The protective group was removed and the double bond was dihydroxylated leading to the target compound. Removal of the protective group was performed using a newly found ecofriendly catalyst for N-Boc deprotection. The final iminosugar derivative 7 and all newly synthesized intermediates, were investigated against S. aureus and E. coli bacteria and were found to show promising activity against both gram-positive and gram-negative bacteria.- (undefined

Novel aziridine esters by the addition of aromatic nitrogen heterocycles to a 2H-azirine-3-carboxylic ester

Methyl 2-(2,6-dichlorophenyl)-2H-azirine-3-carboxoylate acts as an efficient alkylating agent for a variety of five-membered aromatic heterocycles. The aziridines derived from heterocycles that bear an alpha-carbonyl substituent react with TFA to give pyrroloimidazoles; 2,6-dichlorobenzaldehyde is also produced.- (undefined

Exploiting the antiparasitic activity of naphthalimides derivatives

A set of 1,8-naphtalimides derivatives were synthesized and tested against three protozoans that cause important human diseases: Leishmaniainfantum, Trypanosomabrucei and Trypanosomacruzi. Additionally, toxicity was determined by growth inhibition of THP-1 derived macrophages. The results suggest that chemical modifications in the carbon chain linking the naphthalimide and the substituting groups have different effects in the parasites. This work should provide new insights new insights for the design and optimization of more potent and directed naphthalimide derivatives against these organisms.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreements No.602773 (Project KINDRED). L.G. was supported by the Fundaçãopara a Ciência e Tecnologia through grant SFRH/BD/81604/2011.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreements No.602773 (Project KINDRED). Thanks are due also to the NMR Portuguese network (PTNMR, BrukerAvance III 400Univ. Minho), and FCT and FEDER for financial support to CQ/UM.info:eu-repo/semantics/publishedVersio

Synthesis and biological evaluation of mono and bis naphthalimides derivatives against SH-5Y-SY, human brain cancer cells

Naphthalimides (1H-benzo[de]isoquinoline-1,3-(2H)-diones) consists of a flat, generally π-deficient aromatic or heteroaromatic system and show strong hydrophobicity.1 These types of compounds with this moiety showed fluorescence and biological properties such as anticancer, antimicrobial, antitrypanosomal, analgesic, antioxidative and antiviral properties1-2 The naphthalimides compounds are also known to be very good DNA intercalators3, since the planar naphthalimido moiety binds by perpendicular insertion between the base pairs of the double helix of DNA.4 Previous work had already shown that mono and bis naphthalimido derivatives to exhibit strong activity against different cancer cell lines.5-6 Here in this work we would like to demonstrate that the alkyl chain i.e. the linker between the naphthalimido groups or the substituent attached at the end of the linker chain, do have an impact on the biological and DNA binding properties. The synthesis of new mono-naphthalimides derivatives involved the reaction with different aldehydes and with different length of alkyl chain. For the new bis-naphthalimides the reactions consist of an N-alkylation reaction between with different linkers and the corresponding O-tosyl alkylnaphthalimides. The biological activities of the newly synthesized compounds includes their ability to bind DNA, their toxicity against SH-5YSY human brain cancer cells in vitro, cell morphology and cellular uptake will also be presented.info:eu-repo/semantics/publishedVersio