Добірка наукової літератури з теми "Unsaturated sugar"

This investigation is done to select the best composite on bending strength and stiffness derived from different parts of sugar palm fibre reinforced unsaturated polyester composites. Sugar palm tree is one of the most popular natural fibres. The fibre was obtained from the sugar palm tree and mixed with unsaturated polyester (PE). All of the composites are labelled as SPF/PE for sugar palm frond composite, SPB/PE for sugar palm bunch composite, SPT/PE for sugar palm trunk composite and ijuk/PE for black sugar palm fibre composite. The bending strength and stiffness tests were done according to ASTM D 790-(2000). The higher value of bending strength and stiffness obtained by SPT/PE which is 41.906 MPa and 3.363 GPa respectively followed by SPF/PE (38.906 MPa and 3.001 GPa), SPB/PE (35.168 MPa and 2.749) and ijuk/PE (33.742 MPa and 2.424 GPa)

The effect of fibre modification via vacuum resin impregnation on tensile properties of sugar palm fibre reinforced thermosetting composites was studied. The fibres were impregnated with unsaturated polyester, vinylester and epoxy at the pressure of 600mmHg (79.99kPa) for 30 mins. After curing time, it was observed that tensile strength of impregnated fibre was significantly increased with epoxy (EPX) was the best with 188.06 MPa. It was followed by unsaturated polyester (UP) and vinylester (VE) with 107.12 MPa and 158.31 MPa. However, tensile modulus for sugar palm fibre impregnated with EPX increased up to 21% compared to un-impregnated sugar palm fibre followed by UP (12.7%) and VE (8.4%). It was observed that different impregnation agents gave different values of strength of sugar palm fibre composites.

Thioglycollate reacts with the 5′ product of AP lyase activity on apurinic/apyrimidinic (AP) sites in DNA. The 3′-terminal thioglycollate-unsaturated sugar 5-phosphate adduct can be released by the use of Escherichia coli endonuclease IV or endonuclease VI, and identified by DEAE-Sephadex chromatography. In contrast, the mammalian AP endonuclease is unable to excise a 3′-terminal thiol-unsaturated sugar adduct; this lesion, which must sometimes occur in vivo, might be irreparable and have pathological consequences.

Background: Rising prevalence of gastroesophageal reflux disease (GERD) in US Veterans is concurrent with increasing excess body weight. Objective: The objective of this cross-sectional study is to examine relationships between dietary macronutrients, gastrointestinal hormones, and GERD status. Methods: Ninety-eight veterans with overweight/obesity and empiric proton pump inhibitor (PPI) treatment were enrolled from the Tennessee Valley Healthcare System. Subjects had esophageal manometry and 24-h pH monitoring. Subjective symptoms were assessed with Gastroesophageal Reflux Disease Questionnaire (GERDQ) and Symptom Assessment Scale (GSAS). The primary outcomes, total acid exposure time (AET) and number of reflux episodes, enabled categorizing subjects as either pathologic GERD or inconclusive GERD. Data analysis included independent T-tests, Spearman Rho correlations, and multivariable linear regression modeling. Results: Higher intake of sugar-sweetened beverages (sugar-sweetened tea, soda, and fruit juice) associated with higher AET. Higher saturated-to-unsaturated fat intake is associated with higher AET and number of reflux episodes. Overall, sugar-sweetened beverage intake, saturated-to-unsaturated fat ratio, tomato-based food items, glucagon-like polypeptide 1 (GLP-1) level, time of first meal, and education status accounted for a significant amount of the variability in AET. Pathologic GERD subjects reported more heartburn ( p = 0.006), regurgitation ( p = 0.01), acid taste (0.001), and nausea severity ( p = 0.04). GERDQ score associated with AET ( r = 0.31, p = 0.005), but GSAS did not ( r = 0.12, p = 0.28). Conclusion: Of the many foods and nutrients tested, the type (not amount) of carbohydrate (simple sugars) and the type (not amount) of fat (saturated vs unsaturated fat) consumed associated with objective and/or subjective GERD testing. These novel findings contribute to the evidence base guiding specific dietary recommendations in the clinical management of GERD.

Carbohydrate recognition is essential in cellular interactions and biological processes. It is characterized by structural diversity, multivalency and cooperative effects. To evaluate carbohydrate interaction and recognition, the structurally defined attachment of sugar units to a rigid template is highly desired. β-Peptide helices offer conformationally stable templates for the linear presentation of sugar units in defined distances. The synthesis and β-peptide incorporation of sugar-β-amino acids are described providing the saccharide units as amino acid side chain. The respective sugar-β-amino acids are accessible by Michael addition of ammonia to sugar units derivatized as α,β-unsaturated esters. Three sugar units were incorporated in β-peptide oligomers varying the sugar (glucose, galactose, xylose) and sugar protecting groups. The influence of sugar units and the configuration of sugar-β-amino acids on β-peptide secondary structure were investigated by CD spectroscopy.

This thesis presents a finite element solution to the rolling of prepared cane and other two-phase materials. For the first time, modern porous medium mechanics is applied to prepared cane and the rolling and compression of prepared cane is treated as a fully coupled unsaturated-saturated two phase flow problem. The classical Biot theory for fully saturated materials is extended and modified to suit the present project. The finite element method is applied to the governing equations for spatial discretization, followed by both a full rank Newmark scheme and a reduced rank formulation for the time domian discretization. Two analysis methods (steady-state and transient) are presented. The quasi-static .u-P formulation is extensively used in this thesis and verified through numerical computation. Some comments on the implementation of the computer program for the transient direct solution method are also given. A constitutive relation estimated from the finite element simulation of the constrained compression test cell is also given. This is an important contribution of this thesis and leads the way to innovative modelling of milling operations. A more sophisticated finite element inverse analysis method used to determine a constitutive relation for nonlinear two phase materials is also presented, coded and tested. The computational model of the rolling of prepared cane with two rolls is described in detail. The material parameters of prepared cane are described and their variations during the rolling process are derived and discussed. The results of the numerical analysis show that the model and solution procedures are capable of providing realistic predictions and opens the way for further development.

Ce travail de doctorat porte sur la synthèse et utilisation de bicyclolactones glycidiques, de façon à accéder des dérivés de sucres contenant un système carbonylé α,β-insaturé. Trois types de bicyclolactones ont été étudiés: butenolides liés à des cycles furanose, butenolides fusionnés à des cycles pyranose, comprenant S- et NH-analogues et carboxyméthyle glycosides lactones (CMGLs). La méthodologie de synthèse de butenolides sur motif sucre est basée sur l’oléfination de Wittig de 3 ou 5-cétosucres et lactonisation intramoléculaire spontanée de gamma-hydroxyesters α,β-insaturés intermédiaires. Pour la synthèse des systèmes fusionnés, des furano-3-uloses protégés ont été convertis en 3-C-(éthoxycarbonyl)méthylène furanoses. Une hydrolyse acide finale permet la transestérification intramoléculaire et aussi l’isomérization du cycle en forme pyranose. Des précurseurs 5-S et 5-aminofuranosidiques ont conduit à des analogues thiosucres ou à des dérivés glycidiques ayant une fonction amide et un système carbonylé α,β-insaturé, respectivement. Les CMGLs ont été converties en 3-enopyranosid-2-uloses par l’ouverture de la lactone avec une amine et oxydation/élimination du 2-hydroxy pyranoside tri-O-acétylé obtenu. L’oléfination de Wittig subséquente a conduit aux diènes conjugués pyranosidiques ramifiés en C-2. Les glycosides contenant un groupement propargyle ont permis de préparer des 1,2,3-triazoles par ‘click’ chemistry. Quelques molécules ont été soumises à évaluation antimicrobienne et les énulosides de (N-dodécylcarbamoyl)méthyle ont montré les meilleures activités. Le composé le plus actif est l’énuloside-α qui a montré un très fort effet contre des espèces de Bacillus et une forte activité contre Enterococcus faecalis et Penicillium aurantiogriseum. Les diènepyranosides ont révélé une activité forte et sélective contre E. faecalis. Les dérivés triazolés n'ont montré aucune activité. Parmi les composés bioactifs, trois sont avérés peu toxiques chez les cellules eucaryotes
This PhD work was focused on the synthesis and the uses of carbohydrate bicyclic lactones for the access to sugar derivatives comprising an alpha, beta-unsaturated carbonyl function. Three types of bicyclic lactones were investigated: furanose C-C-Iinked butenolides, pyranose-fused butenolides, including S-or NH-analogues and carboxymethyl glycoside lactones (CMGLs). The synthetic methodology for butenolide containing-sugars was based on the Wittig olefination of 3- or 5-keto sugars and spontaneous intramolecular lactonization of the intermediate gamma-hydroxy axy alpha,beta-unsaturated esters. In the case of the fused systems, protected furanos-3-uloses were converted into 3-C-(ethoxycarbonyl)methylene furanoses. Further acid hydrolysis elicited both intramolecular transesterification and isomerization to the pyranose ring. Introduction of a sulfur or a nitrogen function at C-5 of the furanose precursors led to thiosugar analogues or to carbohydrate derivatives comprising both an amide function and an alpha,beta-unsaturated system, respectively. CMGLs were converted into 3-enopyranosid-2-uloses by a sequence involving opening of the lactone moiety by amines and oxidation/elimination of the resulting tri-0-acetylated 2-hydroxy pyranosides. Further Wittig olefination afforded 2-C-branched-chain conjugated dienepyranosides. Glycosides bearing a propargyl moiety were engaged in "click" chemistry reactions leading to 1,2,3-triazoles. Some of the new molecules were submitted to antimicrobial evaluation and (N-dodecylcarbamoyl)methyl enulosides proved to display the best efficacy. The most active one was the a-enuloside which showed very strong effect towards Bacillus species and strong activity against Enterococcus faecalis and the fungal pathogen Penicillium aurantiogriseum. Dienepyranosides exhibited a strong activity selectively towards E. faecalis. Triazole derivatives were virtually ineffective. Three of the bioactive compounds showed low acute toxicity in eukaryotic cells

Unsaturated sugars constitute as an important category of carbohydrate precursors in synthesis. Specifically, 1,2- and 2,3-unsaturated glycosides are excellent intermediates to derivatize monosaccharides and as building blocks in organic synthesis. For example, a major utility of 1,2-unsaturated sugars, namely glycals, is the addition reactions to afford 2-deoxy glycosides under acidic conditions and rearrangement reactions to produce 2,3-unsaturated glycosides. Lewis acids favour the formation of 2,3-unsaturated glycosides, whereas, Brønsted acids lead to normal addition products. A mixture of both the product is obtained often, depending on the nucleophiles and the stereochemistry of glycal. Chapter 1 of the thesis describes (i) reactivities of glycals under acidic condition and (ii) a general survey of reactions involving on C2-C3 carbons of monosaccharides. Glycals are useful precursors to derive a number of functionalized monosaccharide derivatives. A well-known acid catalyzed reaction of glycals is their conversion to 2,3¬unsaturated glycosides, known as the Ferrier products. In a research programme, reactivity switching and selective activation of C-1 or C-3 of 2,3-unsaturated thioglycosides under acid catalyzed condition was undertaken. Thioglycosides are excellent glycosyl donors and can be activated easily. In identifying the reactivities of 2,3-unsaturated thioglycosides, obtained through Ce(IV)-mediated reaction of a glycal, it was intended to study the glycosylation reaction and also the reactivity control of C1-C3 carbons during a glycosylation reaction. Experiments showed that a reactivity switching was possible through activation of either C-1 or C-3. Thus, C-1 glycosylation with alcohol acceptors occurred in the presence of NIS/TfOH, without the acceptors reacting at C-3. On the other hand, reaction of 2,3-unsaturated thioglycosides with alcohols mediated by triflic acid alone led to a transposition of C-1 ethylthio-moiety to C-3 intramolecularly, to form 3-ethylthio-glycals. Resulting glycals underwent glycosylation with alcohols to afford 3-ethylthio-2-deoxy glycosides. However, when thiol was used as an acceptor, only a stereoselective addition at C-3 resulted, so as to form C-1, C-3 dithio-substituted 2-deoxypyranosides. Oxocarbenium ion is the reactive intermediate during activation of a glycosyl donor, and in the case of a 2,3-unsaturated thioglycosides, the oxocarbenium ion may stabilize further by the presence of a C2-C3 unsaturation. Reaction of a nucleophile with allylic oxocarbenium ion may lead to two regio-isomers. Initially, NIS/TfOH was attempted on 2,3–unsaturated sugar with various alcohols and it was found that C-1 was the preferred reactive centre (Scheme 1) Scheme 1 In order to optimize the reaction for selective nucleophilic attack at C-3, further study was continued by using stoichiometric TfOH, in presence of acceptors alcohols with the intension to activate the double bond. The reaction led to the formation of 2-deoxy O-glycosides with the concomitant transposition of C-1 ethylthio-moiety to C-3 (Scheme 2). Scheme 2 An important observation was that the transposition of thioethyl group from C-1 to C-3 was highly regioselective. For example, with thiocresol as the nucleophile, there was an addition across the C-2-C-3 double bond to afford C-1, C-3-dithio derivative (Scheme 2). Thus, hard-soft nature of the nucleophiles, as well as, carbon centres helped to rationalize the reactivites. It was also observed that the intramolecular transposition of thioethyl group is highly stereo-controlled by equatorial C-4 acetoxy group. Thus, thioethyl nucleophile approached selectively at C-3 and afforded trans-diequatorial products. This rationalization was further confirmed through (i) reaction of benzyl protected 2,3-unsaturated thioglycoside, wherein a C-3 epimeric mixture was observed in 1:1 ratio; (ii) galactosyl derivative under similar reaction condition afforded anomeric mixture of 3-(4-methylphenylthio)-O-glycosides, with trans-diaxial orientation of substituent at C-3 (Scheme 3). Scheme 3 These reactions confirmed the role of C-4 substituent on the carbocation at C-3, through the presence or absence of a neighbouring group participation. In summary, in Chapter 2 the selective activation of either anomeric carbon or C-3 with proper choice of activation and reactivity control at each carbon will be described. Thioglycosides are excellent glyosyl donor and their glycosylation reactions were well explored. Upon indentifying the intramolecular transposition of thioalkyl/aryl functionality from C-1 to C-3, further investigations was undertaken to utilize the newly formed carbon sulfur bonds at C-3. Realizing a potential for such 3-alkyl/aryl thio 2-deoxy sugar, the Pummerer rearrangement was investigated. For this purpose, the thioalkyl/aryl moiety at C-3 was oxidized first to a sulfoxide. The resulting sulfoxide was allowed to undergo Pummerer rearrangement to afford vinyl sulfide (Scheme 4), resulting from the elimination of HOAc in the thioacetal formed in situ. Having implemented Pummerer rearrangement on a sugar substrate, synthetic utility of the rearrangement product, namely vinyl sulfide was undertaken. An effort to implement conjugate addition reaction was undertaken, which required the conversion of vinyl sulfide to vinyl sulfoxide in the first step. The conjugate addition reactions were first conducted with alkoxide nucleophiles. The reaction showed that addition of nucleophiles occurred from axial face to furnish manno-configured derivatives as a single diastereomer at sulfinyl sulfur in a moderate yield along with O-deacetylated product. It was also found that O-benzyl protected sugar vinyl sulfoxide was totally resistant to the conjugate addition reaction (Scheme 4). Scheme 4 In order to find the influence of the substituents in sulfoxide moiety in the addition of nucleophiles, additional study was conducted in which a less hindered thioethyl moiety was installed in place of p-tolylthio moiety. To install ethylthio moiety, a similar sequence of reaction was undertaken as described previously in Scheme 4. Conjugate addition reaction with alkoxide nucleophiles was conducted and analysis of the reaction showed that the addition of alkoxides remained similar, leading to the formation of manno-configuration of substituents (Scheme 5). Scheme 5 The configuration of the Michael adducts were ascertained from 1H NMR, as well as 2D NMR spectroscopies. H-1 of all adducts appeared as an apparent singlet, consistent with very small J1,2 values. Aryl vinyl sulfoxide afforded conjugate addition product at much higher ratio than corresponding alkyl vinyl sulfoxide. Thus, among aryl and alkyl vinyl sulfoxides, conjugate addition occurred better with the aryl vinyl sulfoxide, indicating a strong electronic effect of aryl group in stabilizing the conjugate anion which would form in situ during nucleophilic addition with vinyl sulfoxide. Therefore, p-tolylthio substituted vinyl sulfoxide served as a more efficient Michael acceptor when compared to the thioethyl substituted vinyl sulfoxide. Asymmetric environment of vinyl sulfoxides play a vital role during the reaction. Vinyl sulfoxides can exist in two stereochemically distinct conformation which makes the vinyl group electronically dissimilar. In one of the conformer S-O and C-C bonds are coplanar, whereas in the other conformation, these two bonds are opposite to each other. It is agreed generally that vinyl sulfoxides generally try to adopt the most reactive conformer during the reaction in which the C-C and S-O bonds are syn to each other. Thus, the preference for an axial attack would originate from a face anti to the lone pair of electrons on the sulfur of sulfoxide functionality, leading to the formation of the product with manno-configuration. As O-deacetylated vinyl sulfoxide was obtained along with the Michael adducts, it was assumed that one of the epimers of vinyl sulfoxide appeared to be more reactive when compared to the other. Chapter 3 describes implementation of a Pummerer rearrangement in order to synthesize a sugar vinyl sulfoxide and its conjugate addition reactions with alkoxide nucleophiles. The nucleophilic addition reactions of vinyl sulfoxide with other nucleophiles were studied further. The effect of the substituents of chiral sulfoxides in conjugate addition reactions was also incorporated in the course of reactions. Reactions of amines, carbon and sulfur nucleophiles were undertaken with p-tolylthio-substituted vinyl sulfoxides. The reactions showed formation of the addition-elimination products (Scheme 6). All primary amines, carbon and sulfur nucleophiles afforded C-2 axial epimer, namely, threo-epimer exclusively, wherein secondary amines furnished the equatorial vs axial epimer in 3:1 ratio. Scheme 6 In order to assess the course of the reaction, vinyl sulfoxide presenting a p-cumenethio¬moiety was installed in place of p-tolylthio moiety. Conjugate addition reactions were performed with both primary as well as secondary amines that showed formation of the C-2 epimeric mixtures. With both the primary and secondary amines C-2 equatorial epimer was found to be as the major product (Scheme 7). Scheme 7 In conjugate addition of vinyl sulfoxides, nucleophiles approach the olefinic face preferentially, which is anti to the electron rich sulfur lone pair of electrons and syn to the bulky aryl group. Therefore, C-2 axial epimer was observed as most favourable product. However, secondary amines remarkably influenced the pattern as well as selectivity of the reaction. Steric considerations were likely to dictate the overall reactivity with secondary amines which was even more pronounced when using p-cumenethio-substituted vinyl sulfoxide. Chapter 4 describes the conjugate additions as well as remote effect of aryl substituent on the selectivity of addition of amines on sugar sulfoxide In summary, the Thesis establishes: A new reactivity of switching and a selective activation of 2,3-unsaturated thioglycoside; A Pummerer rearrangement route in order to synthesize sugar vinyl sulfide for the first time, which on selective oxidation furnish a sugar vinyl sulfoxide, a useful precursor for conjugate addition reactions; An assessment of the stereoelectronic, as well as, steric effect of the chiral vinyl sulfoxide with various nucleophiles in conjugate addition reactions; Influence of the protecting groups were also studied in conjugate addition reactions. Overall the study presented in the Thesis provides a new insight to unsaturated sugars. The salient features of the present findings also showed that the intermediates such as C-3 substituted thioalkyl/aryl glycosides, vinyl sulfides, a variety of new C-2 substituted vinyl sulfoxides are also the potential sites for many types of modifications in monosaccharides. (For structural formula pl see the pdf file)

Unsaturated sugars constitute as an important category of carbohydrate precursors in synthesis. Specifically, 1,2- and 2,3-unsaturated glycosides are excellent intermediates to derivatize monosaccharides and as building blocks in organic synthesis. For example, a major utility of 1,2-unsaturated sugars, namely glycals, is the addition reactions to afford 2-deoxy glycosides under acidic conditions and rearrangement reactions to produce 2,3-unsaturated glycosides. Lewis acids favour the formation of 2,3-unsaturated glycosides, whereas, Brønsted acids lead to normal addition products. A mixture of both the product is obtained often, depending on the nucleophiles and the stereochemistry of glycal. Chapter 1 of the thesis describes (i) reactivities of glycals under acidic condition and (ii) a general survey of reactions involving on C2-C3 carbons of monosaccharides. Glycals are useful precursors to derive a number of functionalized monosaccharide derivatives. A well-known acid catalyzed reaction of glycals is their conversion to 2,3¬unsaturated glycosides, known as the Ferrier products. In a research programme, reactivity switching and selective activation of C-1 or C-3 of 2,3-unsaturated thioglycosides under acid catalyzed condition was undertaken. Thioglycosides are excellent glycosyl donors and can be activated easily. In identifying the reactivities of 2,3-unsaturated thioglycosides, obtained through Ce(IV)-mediated reaction of a glycal, it was intended to study the glycosylation reaction and also the reactivity control of C1-C3 carbons during a glycosylation reaction. Experiments showed that a reactivity switching was possible through activation of either C-1 or C-3. Thus, C-1 glycosylation with alcohol acceptors occurred in the presence of NIS/TfOH, without the acceptors reacting at C-3. On the other hand, reaction of 2,3-unsaturated thioglycosides with alcohols mediated by triflic acid alone led to a transposition of C-1 ethylthio-moiety to C-3 intramolecularly, to form 3-ethylthio-glycals. Resulting glycals underwent glycosylation with alcohols to afford 3-ethylthio-2-deoxy glycosides. However, when thiol was used as an acceptor, only a stereoselective addition at C-3 resulted, so as to form C-1, C-3 dithio-substituted 2-deoxypyranosides. Oxocarbenium ion is the reactive intermediate during activation of a glycosyl donor, and in the case of a 2,3-unsaturated thioglycosides, the oxocarbenium ion may stabilize further by the presence of a C2-C3 unsaturation. Reaction of a nucleophile with allylic oxocarbenium ion may lead to two regio-isomers. Initially, NIS/TfOH was attempted on 2,3–unsaturated sugar with various alcohols and it was found that C-1 was the preferred reactive centre (Scheme 1) Scheme 1 In order to optimize the reaction for selective nucleophilic attack at C-3, further study was continued by using stoichiometric TfOH, in presence of acceptors alcohols with the intension to activate the double bond. The reaction led to the formation of 2-deoxy O-glycosides with the concomitant transposition of C-1 ethylthio-moiety to C-3 (Scheme 2). Scheme 2 An important observation was that the transposition of thioethyl group from C-1 to C-3 was highly regioselective. For example, with thiocresol as the nucleophile, there was an addition across the C-2-C-3 double bond to afford C-1, C-3-dithio derivative (Scheme 2). Thus, hard-soft nature of the nucleophiles, as well as, carbon centres helped to rationalize the reactivites. It was also observed that the intramolecular transposition of thioethyl group is highly stereo-controlled by equatorial C-4 acetoxy group. Thus, thioethyl nucleophile approached selectively at C-3 and afforded trans-diequatorial products. This rationalization was further confirmed through (i) reaction of benzyl protected 2,3-unsaturated thioglycoside, wherein a C-3 epimeric mixture was observed in 1:1 ratio; (ii) galactosyl derivative under similar reaction condition afforded anomeric mixture of 3-(4-methylphenylthio)-O-glycosides, with trans-diaxial orientation of substituent at C-3 (Scheme 3). Scheme 3 These reactions confirmed the role of C-4 substituent on the carbocation at C-3, through the presence or absence of a neighbouring group participation. In summary, in Chapter 2 the selective activation of either anomeric carbon or C-3 with proper choice of activation and reactivity control at each carbon will be described. Thioglycosides are excellent glyosyl donor and their glycosylation reactions were well explored. Upon indentifying the intramolecular transposition of thioalkyl/aryl functionality from C-1 to C-3, further investigations was undertaken to utilize the newly formed carbon sulfur bonds at C-3. Realizing a potential for such 3-alkyl/aryl thio 2-deoxy sugar, the Pummerer rearrangement was investigated. For this purpose, the thioalkyl/aryl moiety at C-3 was oxidized first to a sulfoxide. The resulting sulfoxide was allowed to undergo Pummerer rearrangement to afford vinyl sulfide (Scheme 4), resulting from the elimination of HOAc in the thioacetal formed in situ. Having implemented Pummerer rearrangement on a sugar substrate, synthetic utility of the rearrangement product, namely vinyl sulfide was undertaken. An effort to implement conjugate addition reaction was undertaken, which required the conversion of vinyl sulfide to vinyl sulfoxide in the first step. The conjugate addition reactions were first conducted with alkoxide nucleophiles. The reaction showed that addition of nucleophiles occurred from axial face to furnish manno-configured derivatives as a single diastereomer at sulfinyl sulfur in a moderate yield along with O-deacetylated product. It was also found that O-benzyl protected sugar vinyl sulfoxide was totally resistant to the conjugate addition reaction (Scheme 4). Scheme 4 In order to find the influence of the substituents in sulfoxide moiety in the addition of nucleophiles, additional study was conducted in which a less hindered thioethyl moiety was installed in place of p-tolylthio moiety. To install ethylthio moiety, a similar sequence of reaction was undertaken as described previously in Scheme 4. Conjugate addition reaction with alkoxide nucleophiles was conducted and analysis of the reaction showed that the addition of alkoxides remained similar, leading to the formation of manno-configuration of substituents (Scheme 5). Scheme 5 The configuration of the Michael adducts were ascertained from 1H NMR, as well as 2D NMR spectroscopies. H-1 of all adducts appeared as an apparent singlet, consistent with very small J1,2 values. Aryl vinyl sulfoxide afforded conjugate addition product at much higher ratio than corresponding alkyl vinyl sulfoxide. Thus, among aryl and alkyl vinyl sulfoxides, conjugate addition occurred better with the aryl vinyl sulfoxide, indicating a strong electronic effect of aryl group in stabilizing the conjugate anion which would form in situ during nucleophilic addition with vinyl sulfoxide. Therefore, p-tolylthio substituted vinyl sulfoxide served as a more efficient Michael acceptor when compared to the thioethyl substituted vinyl sulfoxide. Asymmetric environment of vinyl sulfoxides play a vital role during the reaction. Vinyl sulfoxides can exist in two stereochemically distinct conformation which makes the vinyl group electronically dissimilar. In one of the conformer S-O and C-C bonds are coplanar, whereas in the other conformation, these two bonds are opposite to each other. It is agreed generally that vinyl sulfoxides generally try to adopt the most reactive conformer during the reaction in which the C-C and S-O bonds are syn to each other. Thus, the preference for an axial attack would originate from a face anti to the lone pair of electrons on the sulfur of sulfoxide functionality, leading to the formation of the product with manno-configuration. As O-deacetylated vinyl sulfoxide was obtained along with the Michael adducts, it was assumed that one of the epimers of vinyl sulfoxide appeared to be more reactive when compared to the other. Chapter 3 describes implementation of a Pummerer rearrangement in order to synthesize a sugar vinyl sulfoxide and its conjugate addition reactions with alkoxide nucleophiles. The nucleophilic addition reactions of vinyl sulfoxide with other nucleophiles were studied further. The effect of the substituents of chiral sulfoxides in conjugate addition reactions was also incorporated in the course of reactions. Reactions of amines, carbon and sulfur nucleophiles were undertaken with p-tolylthio-substituted vinyl sulfoxides. The reactions showed formation of the addition-elimination products (Scheme 6). All primary amines, carbon and sulfur nucleophiles afforded C-2 axial epimer, namely, threo-epimer exclusively, wherein secondary amines furnished the equatorial vs axial epimer in 3:1 ratio. Scheme 6 In order to assess the course of the reaction, vinyl sulfoxide presenting a p-cumenethio¬moiety was installed in place of p-tolylthio moiety. Conjugate addition reactions were performed with both primary as well as secondary amines that showed formation of the C-2 epimeric mixtures. With both the primary and secondary amines C-2 equatorial epimer was found to be as the major product (Scheme 7). Scheme 7 In conjugate addition of vinyl sulfoxides, nucleophiles approach the olefinic face preferentially, which is anti to the electron rich sulfur lone pair of electrons and syn to the bulky aryl group. Therefore, C-2 axial epimer was observed as most favourable product. However, secondary amines remarkably influenced the pattern as well as selectivity of the reaction. Steric considerations were likely to dictate the overall reactivity with secondary amines which was even more pronounced when using p-cumenethio-substituted vinyl sulfoxide. Chapter 4 describes the conjugate additions as well as remote effect of aryl substituent on the selectivity of addition of amines on sugar sulfoxide In summary, the Thesis establishes: A new reactivity of switching and a selective activation of 2,3-unsaturated thioglycoside; A Pummerer rearrangement route in order to synthesize sugar vinyl sulfide for the first time, which on selective oxidation furnish a sugar vinyl sulfoxide, a useful precursor for conjugate addition reactions; An assessment of the stereoelectronic, as well as, steric effect of the chiral vinyl sulfoxide with various nucleophiles in conjugate addition reactions; Influence of the protecting groups were also studied in conjugate addition reactions. Overall the study presented in the Thesis provides a new insight to unsaturated sugars. The salient features of the present findings also showed that the intermediates such as C-3 substituted thioalkyl/aryl glycosides, vinyl sulfides, a variety of new C-2 substituted vinyl sulfoxides are also the potential sites for many types of modifications in monosaccharides. (For structural formula pl see the pdf file)

2,3- Dideoxy sugars are versatile synthons for organic synthesis. The applications are diverse in biological systems and organic synthesis. In the first part of the thesis, 2,3-unsaturated sugars are used for the glycoconjugation of amino acids, peptides and proteins. In the later part, 2,3-dideoxy sugar is used to synthesize carbohydrate macrocycle. Finally, sugar vinyl sulfoxide is used to synthesize substituted pyran via 2,6- anhydro sugar formation. Chapter 1 of the thesis is divided into two parts. The first part describes the literature on unsaturated sugar, especially 2,3-unsaturated sugars, synthesis and their modifications. Attention is given to their addition reactions with nucleophiles and conjugation with biomolecules. A brief introduction to glycoconjugation is also reported in this part. Different glycoconjugation methods are discussed briefly, and the advantages are compared accordingly. The second part of this chapter elaborates on the synthesis of cyclic oligosaccharides. The approaches and the difficulties in the respective approaches are mentioned accordingly. Challenges with synthesising small cyclic oligosaccharides are cited according to the available literature. Current development in the field is also covered in the discussion. Chapter 2 of the thesis deals with the glycoconjugation methods using sugar vinyl sulfoxide involving Michael addition reaction. Glycoconjugations of amino acids, peptides and protein, namely lysozyme are demonstrated in benign physiological conditions. The smaller glycoconjugated molecules are characterized with the help of NMR spectroscopy and mass spectrometry, while the larger glycoconjugated peptide and protein are characterized with the help of mass spectrometry. Biophysical studies of glycoconjugated lysozyme showed increased stability in the presence of trypsin while retaining its antimicrobial activity. Thus, a benign glycoconjugation method is developed. Chapter 3 of the thesis unravels further potential of glycoconjugation using sugar vinyl sulfoxide. PETIM dendrimers of generation zero to three are glycoconjugated with sugar vinyl sulfoxide. The glycoconjugations of the lower generation dendrimers are confirmed using NMR spectroscopy and mass spectrometry; for higher generations, only NMR spectroscopy was employed for the characterization. The first-order reaction rate constant of the glycoconjugation reaction is also determined using NMR spectroscopy. Further biological evaluation of the native and glycoconjugated PETIM dendrimer reveals that PETIM dendrimers show selective antibacterial activity against M. smegmatis, and the native dendrimers show higher efficacy over the glycoconjugated dendrimer. Chapter 4 of the thesis describes the synthesis of the cyclic disaccharide molecule composed of 2,3-dideoxy furanoside monomer units. The synthesis started from protected glucal molecules and followed a few simple reaction steps, including the Ferrier reaction, desulfurization reaction, and selective hydroxy group protection and finally, glycoconjugation reaction. While the formation of the disaccharide is confirmed using NMR spectroscopy and mass spectrometry, the conformation of the constituting monomeric unit of the cyclic disaccharide is ascertained through solid state structure determination using the single crystal X-ray diffraction method. The ring contraction of the pyranoside monomer to furanoside cyclic disaccharide is explained by two plausible mechanisms involved in the glycosylation step. Further encapsulation property of the cyclic disaccharide molecule was evaluated against the 1-aminoadamantane using the ITC method. This experiment allows looking into the thermodynamics of the encapsulation and the encapsulation mode of the molecule. Chapter 5 of the thesis shows sugar vinyl sulfoxide's application and potential as a synthetic intermediate. Intra-molecular Michael addition reaction of the sugar vinyl sulfoxide in basic condition affords elusive 2,6-anhydro sugar molecules in a single step. Selective opening of the bicyclic ring of the anhydro sugar converts it to a substituted pyran. The applicability of this two-step, one-pot reaction is also tested on sugar vinyl sulfoxide derived from galactal. The thesis describes the achievement of the diversification of 2,3-unsaturated sugar. A benign glycoconjugation method is developed and adequately characterized. The synthetic potential of 2,3-dideoxy sugar is demonstrated through the synthesis of cyclic disaccharide via a ring contraction of pyranoside to a furanoside. And finally, a two-step reaction protocol converts pyranoside sugar into a substituted pyran.

Tese de doutoramento, Química (Química Orgânica), Universidade de Lisboa, Faculdade de Ciências, 2011
This PhD research work was focused on the synthesis and uses of bicyclic carbohydrate lactones, in the context of the access to new sugar derivatives containing an α,β- unsaturated carbonyl function. These molecular targets, chosen for the intrinsic bioactivity associated to the conjugated carbonyl system, were synthesized and submitted to biological evaluation, particularly their effect towards fungi and bacteria. Moreover, the inclusion of conjugated carbonyl systems in carbohydrates provides suitable templates for further derivatization, to which a variety of reactions may be applied. Three types of bicyclic sugar lactones were investigated: furanose C-C-linked butenolides (compounds type I), pyranose-fused butenolides, including S- or NHanalogues (compounds type II-IV), and carboxymethyl glycoside-derived lactones (CMGLs, compounds type V). The access to butenolide containing-sugars was explored. The synthetic methodology was based on the Wittig olefination of easily prepared 3- or 5-keto sugars and spontaneous intramolecular lactonization of the intermediate g-hydroxy α,β-unsaturated esters. In the case of the bicyclic fused derivatives, furanos-3-uloses containing acid labile 5-O or 5,6-di-O-protecting groups were used as precursors and converted into the corresponding (Z)- or (E)-3-C-(ethoxycarbonyl)methylene furanoses. Further acidmediated hydrolysis made possible their isomerization to the pyranose ring and concomitant intramolecular transesterification leading directly to the target compounds in good overall yields. Such bicyclic systems featured the butenolide moiety annelated at C-2-C-3 (compounds type II) or at C-3-C-4 of the sugar backbone, depending on the stereochemistry of the C3-C3’double bond. The introduction of a sulfur function at C-5 of the furanoid 3-C-α,β-unsaturated esters, widened the scope of this methodology to thiosugar analogues of type III. When this approach was applied to related 5-azido furanoid esters aiming at imino sugar-based molecules of type IV, different carbohydrate derivatives comprising both an amide functionality and an α,b-unsaturated carbonyl system were obtained. The (E)- and (Z)-3-C-(ethoxycarbonyl)methylene 5- amino furanoses were converted to a furanose-fused α,β-unsaturated δ-lactam and to a butenolide-containing N-ethylformamide, respectively. Moreover, the hydrolysis of the 1,2-O-isopropylidene group of the (Z)-5-azido furanose precursor, followed by azide reduction, provided a 2-keto iminopyranose, which led to the 1,2-dihydropyridin-3-one system upon acetylation. CMGLs (compounds type V) were used as precursors for 3-enopyranosid-2-uloses (compounds type VI). The opening of the lactone moiety by amines provided tri-Oacylated 2-hydroxy pyranosides which by oxidation/elimination generated the enone system. Further Wittig olefination afforded 2-C-branched-chain conjugated dienepyranosides (compounds type VII). Glycosides bearing a propargyl moiety were engaged in “click” chemistry reactions leading to the corresponding 1,2,3-triazoles (compounds type VIII-IX). Among the molecular targets obtained, the furanose-linked butenolides, the pyranosefused butenolides, the conjugated carbonyl sugar derivatives synthesized from CMGLs and the triazole-containing glycosides were submitted to antimicrobial activity assays. The butenolide-containing sugars did not show satisfactory antibacterial or antifungal activities. Such weak effect is probably due to the presence of a quaternary β-carbon in the conjugated system of these molecules, which is specially hindered in the fused systems, reducing their Michael acceptor ability. In contrast, significant efficacy was observed for 3-enopyranosid-2-uloses and conjugated diene pyranosides. In particular, (N-dodecylcarbamoyl)methyl enulosides displayed strong and very strong activities against some of the pathogen microbes tested, being in some cases similar to those of the standard antibiotics. The α-enuloside exhibited very strong effect towards Bacillus cereus and Bacillus subtillis and strong activity against Enterococcus faecalis and the fungal pathogen Penicillium aurantiogriseum. The β-anomer presented a very strong inhibitory effect against the fungi Aspergillus niger and Penicillium aurantiogriseum. Dienepyranosides exhibited a strong activity selectively towards Enterococcus faecalis. Triazole derivatives were virtually ineffective. Three of the bioactive compounds, including the most active one, i.e. the α-(N-dodecylcarbamoyl)methyl enuloside, showed low acute toxicity in eukaryotic hepatoma cells.
O trabalho desenvolvido no âmbito deste Doutoramento centrou-se na síntese e no uso de biciclolactonas glicídicas com o objectivo de se obterem novos derivados de açúcares contendo um sistema carbonílico α,β-insaturado na sua estrutura. Estes alvos moleculares foram sintetizados no sentido de se avaliarem posteriormente as suas propriedades biológicas, nomeadamente a nível de actividade antifúngica e antibacteriana. O sistema carbonílico α,β-insaturado é frequentemente encontrado em produtos naturais e de síntese que possuem uma variedade de actividades biológicas. A bioactividade exibida por estes compostos está geralmente associada à capacidade da função conjugada para reagir segundo adição de Michael com nucleófilos existentes em proteínas. Em particular, derivados de açúcares contendo lactonas α,β-insaturadas foram descritos como fungicidas ou como insecticidas potentes. Por outro lado, a inclusão destas unidades em carbo-hidratos conduz a moléculas funcionalizadas que poderão ser úteis para posterior derivatização, devido à reactividade do sistema conjugado. As moléculas-alvo tiveram como base três tipos de lactonas bicíclicas (Fig. 1): butenolidas ligadas a anéis de furanose (compostos tipo I), butenolidas fundidas a anéis de pyranose, incluindo tio- e iminoaçúcares análogos (compostos tipo II-IV), e lactonas derivadas de glicósidos de carboximetilo (compostos tipo V). A síntese de açúcares contendo butenolidas foi desenvolvida e implementada uma metodologia que envolveu a olefinação de Wittig de 3- ou 5-cetoaçúcares e a lactonização intramolecular expontânea de intermediários γ-hidroxiésters α,β- insaturados formados. Os 5-cetoaçúcares precursores de butenolidas ligadas a furanoses foram obtidos por meio de oxidação selectiva do grupo hidroxilo secundário de 5,6- dióis derivados de 1,2-O-isopropilideno-α-D-glucofuranose e/ou -alofuranose (1-4, Esquema 1). O oxidante utilizado foi o sistema Bu2OSn/NBS (N-bromosuccinimida), dando origem às α-hidroxicetonas desejadas 5-8 com bons rendimentos. A estereoselectividade da reacção de Wittig subsequente com [(etoxicarbonil)metileno]trifenilfosforano foi influenciada pela configuração do substituinte em C-3. Os derivados com configuração xilo 5 e 6 originaram apenas γ- hidroxiésteres insaturados (9, 10) com estereoquímica (Z). Contudo, utilizando as α- hidroxicetonas com configuração ribo 7 e 8, a reacção de Wittig foi estereosseletiva para a formação dos (E)-isómeros, cuja transesterificação intramolecular espontânea deu origem às correspondentes lactonas α,β-insaturadas 13 e 14. Os (Z)-isómeros (11 e 12) foram neste caso produtos minoritários da reacção. A estratégia implementada para a síntese de butenolidas fundidas a piranoses (compostos tipo II, Fig. 1) baseou-se na olefinação de Wittig de derivados 1,2-Oisopropilideno- α-D-pento- ou-hexofuranos-3-ulose, 5-O- ou 5,6-di-O-protegidos com grupos lábeis em meio ácido, seguida de hidrólise ácida. Nestas condições, com a remoção dos grupos protectores, além da reacção de transesterificação intramolecular que leva à formação da lactona, também ocorre isomerização furanose → piranose, conduzindo à síntese das moléculas alvo num só passo. A olefinação de Wittig dos 3-cetoaçúcares 15 e 16 foi estereosselectiva para a formação dos respectivos ésteres (Z)-α,β-insaturados 17a e 18a (Esquema 2). O tratamento de 17a e 18a com a resina ácida Amberlite em refluxo de metanol durante 16 h levou à formação dos compostos-alvo 19 e 21. As condições experimentais de hidrólise de 17a foram optimizadas de modo a reduzir o tempo de reacção para a obtenção do composto bicíclico 19 e também para permitir a formação do correspondente glicósido de metilo 20. A hidrólise de 17a com uma solução aquosa de ácido trifluoroacético (TFA) a 60%, à temperatura ambiente, conduziu ao composto bicíclico desejado 19 em apenas 5 min, com um rendimento de 90%. Utilizando a resina Dowex 50-W, a conversão de 17a em 19 foi completa ao fim de 2 h e, após 16 h de reacção, obteve-se o glicósido de metilo 20. A síntese de um derivado bicíclico regiosselectivamente protegido no grupo hidroxilo primário (composto 25, Esquema 3) foi realizada a partir da monoprotecção selectiva do diol 22 com cloreto de pivaloílo seguida da hidrólise em meio ácido. Analogamente e seguindo a mesma estratégia de síntese, a partir dos ésteres (E)- insaturados 17b e 18b, foram obtidos, com sucesso, os compostos 26-28, nos quais a unidade butenolida está fundida ao anel de piranose nas posições 3 e 4 (Fig. 2). No entanto não se verificou lactonização após remoção do grupo 1,2-isopropilideno do derivado 5,6-di-O-pivaloílado 24, e dos derivados pentofuranóides com configuração erythro, possuindo um grupo pivaloilo em C-5 (29) ou desoxigenado em C-5 (30), nas condições hidrolíticas descritas e obtiveram-se os respectivos dióis 31-33 (Esquema 4). Estes resultados indicam que a fusão de lactonas insaturadas de cinco membros a anéis de furanose é desfavorável, ocorrendo preferencialmente em sistemas de piranose. A eficácia e a conveniência desta metodologia para a obtenção de análogos tioaçúcares e iminoaçúcares (compostos tipo III e IV, Fig. 1), a partir de furanos-3-uloses, foram também investigadas. A estas duas classes de miméticos de carbo-hidratos está frequentemente associada uma variedade de propriedades biológicas, nomeadamente a capacidade de inibição de glicosidases. O interesse neste tipo de estruturas reside também no seu potencial sintético como precursores para novos derivados de tio- e iminoaçúcares. A síntese de butenolidas fundidas a tioaçúcares involveu a introdução de uma função sulfidrílica em C-5 nos derivados (Z)-3-C-(etoxicarbonil)metileno pento- ou hexofuranóides 34 e 35 por meio de substituição nucleófila de um grupo tosilato ou de um triflato, respectivamente, por um grupo tioacetilo (Esquema 5). A remoção dos grupos éster de 36, 37 seguida de hidrólise ácida deu origem aos compostos bicíclicos desejados 38 e 39. A posterior acetilação de 38 e 39 conduziu aos derivados acetilados 40 e 41 e aos tioglicais correspondentes 42 e 43, por eliminação de ácido acético. A acetilação de 39 conduziu maioritariamente ao tioglical 43, o que pode ser explicado pela baixa estabilidade conformacional de 41, devido à presença de um grupo acetoximetilo pseudoaxial. A eliminação em C-1,C-2 não só resulta num sistema conjugado altamente estável, mas no caso de 41 permite a adopção de uma conformação sofá relativamente estável. Para a investigação da síntese de iminoaçúcares do tipo IV foram sintetizados os precursores 5-azido-3-C-(etoxicarbonil)metileno furanoses (44, Esquema 6). A redução do grupo azida do éster (Z)-α,β-insaturado 44a pelo método de Staudinger resultou na respectiva amina 45. A hidrólise de 45 em meio ácido seguida de adição de base para neutralizar o ácido em excesso, resultou no derivado da etilformamida contendo uma butenolida 47. A formação do composto 47 involve o intermediário bicíclico 46, o qual em meio básico é desprotonado no grupo hidroxilo anomérico. O ião resultante rearranja para um ião enolato estabilizado por ressonância, que é protonado em C-2. A hidrólise ácida do grupo 1,2-O-isopropilideno de 44a e posterior redução da função azida do diol 48, de modo a permitir a isomerização 5-aminofuranose/iminopiranose em meio neutro, resultou num 2-cetoiminoaçúcar que por acetilação originou a 1,2-dihidropiridin- 3-ona 49. A redução do grupo azida do (E)-isómero (44b) deu origem à δ- lactama bicíclica 51 por ciclização intramolecular expontânea do δ-aminoéster α,β- insaturado 50. Os derivados 5-aminofuranóides revelaram portanto uma reactividade distinta relativamente aos análogos 5-O e 5-S, que em condições reaccionais semelhantes originaram as butenolidas bicíclicas alvo. As biciclolactonas derivadas de glicósidos de carboximetilo (CMGLs, compostos tipo V, Fig. 1), cuja preparação envolve 2-3 etapas a partir de açúcares livres, foram utilizadas como precursores de cetonas piranóides α,β-insaturadas do tipo hex-3- enopiranosid-2-ulose e de dienopiranósidos conjugados (compostos tipo VI-VII, Fig. 3). A inclusão de uma unidade 1,2,3-triazole, um heterociclo com potencial para conferir bioactividade, para a obtenção de derivados do tipo VIII-IX, foi também investigada. A preparação de cetonas α,β-insaturadas do tipo VI consistiu na abertura nucleófila de CMGLs 52-54 com aminas primárias, seguida de oxidação dos aductos resultantes e eliminação concomitante de ácido acético nas posições 3,4 (Esquema 7). O método de oxidação utilizando o sistema dimetilsulfóxido (DMSO)/anidrido acético (Ac2O) revelou ser o mais eficaz em experiências preliminares e permitiu a obtenção do sistema enona com melhores rendimentos, em relação a outros métodos de oxidação mais suaves. Os 2-hidroxipyranósidos tri-O-acetilados 55-57, 61 com configuração α, conduziram às respectivas enonas 62-64 com bons rendimentos. No entanto, os rendimentos para a oxidação/eliminação dos aductos β (58-60) foram baixos e as respectivas enonas 65-67 demonstraram a sua tendência para a decomposição. Estes resultados devem-se à conformação adoptada por estes compostos, tal como verificado por 1H RMN. Enquanto as enonas 62-64 adoptam uma conformação do tipo envelope OE (sofá), os respectivos anómeros β adoptam uma conformação EO, que é menos estável devido às interacções 1,3-diaxiais. As cetonas α,β-insaturadas foram posteriormente convertidas nos correspondentes dienopiranósidos de cadeia ramificada em C-2 (68-70) por olefinação de Wittig com [(etoxicarbonil)metileno]trifenilfosforano. A configuração (E) da ligação dupla exocíclica foi demonstrada através de NOESY. As reacções de cicloadição dos glicósidos de (N-propargilcarbamoil)metilo 55, 58 e 61 com azoteto de benzilo por meio de um protocolo alternativo de ‘click’ chemistry, tendo como base um catalisador heterogéneo de CuI suportado em Amberlist A-21, deu origem aos triazoles correspondentes 71-73. Os derivados desprotegidos 74-76 foram seguidamente obtidos por desacetilação com NEt3 em metanol e água. A síntese dos compostos do tipo VIII e IX, os quais associam numa molécula um sistema carbonílico conjugado a uma unidade triazole, foi realizada posteriormente (Esquema 8). A oxidação/eliminação de 71 conduziu à 3-enopiranosid-2-ulose 77. O acoplamento do dieno piranósido conjugado 68 com azoteto de benzilo originou o triazole correspondente 78. Entre os alvos moleculares obtidos, os derivados bicíclicos nos quais uma butenolida se encontra ligada a um anel de furanose (compostos tipo I), as butenolidas fundidas a anéis de piranose (compostos tipo II), os derivados piranóides contendo um sistema carbonílico conjugado sintetizados a partir dos precursores CMGLs (compostos tipo VI-VII) e os glicósidos contendo uma unidade triazole (compostos tipo VIII-IX), foram submetidos a testes de actividade antimicrobiana. Foi investigada a inibição de fungos fitopatogénicos e de fungos patogénicos para seres humanos e animais. Foi também feito um estudo sobre a actividade inibidora dos compostos relativamente a bactérias Gram-negativas e Gram-positivas. Os derivados de açúcares contendo butenolidas apresentaram fraca actividade antimicrobiana ou não a exibiram de modo significativo. Estes resultados sugerem uma reduzida aptidão destas moléculas para reagir segundo a adição de Michael, o que se explica pela presença de um C-β quaternário no sistema conjugado, que é estereoquimicamente impedido nas estruturas fundidas. No entanto, os resultados da avaliação biológica das 3-enopiranosid-2-uloses e dos dienopiranósidos de cadeia ramificada revelaram actividades antimicrobianas significativas. Os enulósidos de (N-dodecilcarbamoil)metilo 64 e 67 exibiram actividades fortes ou muito fortes contra alguns dos micróbios testados, demonstrando nalguns casos efeitos inibitórios comparáveis aos dos antibióticos de referência. O enulósido-α (64) revelou actividade muito forte relativamente às bactérias Bacillus cereus e Bacillus subtillis e actividade forte contra Enterococcus faecalis e o fungo Penicillium aurantiogriseum. O anómero-β (67) exibiu um efeito inibitório muito forte contra os fungos Aspergillus niger e Penicillium aurantiogriseum. Os dienopiranósidos conjugados 68-70 revelaram actividade selectiva e forte relativamente a Enterococcus faecalis. Os derivados contendo triazole não demonstraram actividade antimicrobiana significativa. Três dos compostos considerados bioactivos, o α-enulósido de (Ndodecilcarbamoil) metilo 64, e os dienopiranósidos 68 e 69, mostraram ser pouco tóxicos quando submetidos a testes de toxicidade em células eucarióticas hepáticas.
FCT (for the support of the project POCI-PPCDT/QUI/59672/2004 and for the PhD grant SFRH/BD/39251/2007), CPU/CRUP (for a joint Portuguese-French research program), MESER and CNRS

Approximately 65% of patients with T2DM die as a result of cardiovascular disease with hyperglycemia and hyperlipidemia being important risk factors for cardiovascular diseases. Both T2DM and atherosclerosis are considered to be inflammatory processes Human T-lymphocytes (T-cells) and aortic endothelial cells (HAEC) have been shown to be components of plaque formation in atherosclerosis. T cells and HAEC are unique in that in their naive state they have no insulin receptors responsive to insulin but become activated in vitro hyperglycemia and in vivo hyperglycemic conditions such as diabetic ketoacidosis and non-ketotic hyperglycemic conditions. Our studies show that T-cells and HAEC in the presence of high concentrations of glucose /and or the saturated fatty acid (SFA) palmitic acid become activated and express insulin receptors, reactive oxygen species (ROS), cytokine elevation, and lipid peroxidation in a time and concentration-dependent manner. Whereas, the unsaturated fatty acid α-linoleic, was not able to activate these cells and had a salutary effect on the activation by glucose and palmitic acid. We have demonstrated that unsaturated fatty acids (UFA) may provide a protective mechanism against the prooxidant effects of hyperglycemia and high SFA such as palmitic acid. Therefore, diet alternations may be beneficial for decreasing hyperglycemia and cardiovascular risks. Studies have shown that lifestyle changes of diet and exercise can reduce the risk of developing diabetes by 58%. Hyperglycemia and hyperlipidemia are important risk factors of developing diabetes and cardiovascular disease. Therefore, we studied the effects of a High Protein diet versus a High Carbohydrate diet in obese non-diabetic, prediabetic and diabetic subjects for effects on weight loss, blood sugar, lipid levels, inflammation, and oxidative stress.

A solution is a homogeneous mixture of two or more substances. It is usually made up of a solute and a solvent. Generally, Solute+Solvent = Solution A solute is any substance that is dissolved in a solvent. For example, when granulated sugar dissolves in water to give a clear sugar solution, the sugar is the solute, while water is the solvent. Relative to the solvent, a solute is usually present in small amounts. A solvent is any substance in which a solute dissolves. It is usually the part of the solution that is present in the largest amount. Two liquids are said to be miscible if they form a single phase (homogeneous solution) or dissolve in each other in all proportions. For example, ethanol and water are miscible. If two liquids do not form a single phase (or do not dissolve in each other) in any appreciable amount, they are said to be immiscible. For example, water and oil are immiscible. When mixed, they separate into two distinct layers. Substances that are only slightly soluble in a given solvent are said to be insoluble. An aqueous solution is one in which water is the solvent. A dilute solution is one that contains a small amount of solute compared to the maximum amount the solvent can dissolve at that temperature. A concentrated solution is one that contains a large amount of solute compared to the maximum amount the solvent can dissolve at that temperature. A saturated solution is one that is in equilibrium with undissolved solute at a given temperature and pressure: Solute(solid) ⇌ Solute(dissolved) In other words, it contains the maximum amount of solute that can be dissolved at that particular temperature. An unsaturated solution contains less solute than the maximum amount (saturated solution) possible at the same temperature. A supersaturated solution is a solution that contains more solute than the saturated solution at the same temperature. This type of solution is very unstable. When it is agitated, or a speck of the solute is added to it, the excess solute will begin to crystallize out rapidly from the solution until the concentration becomes equal to that of the saturated solution.

Sesame (Sesamum indicum L.) is one of the traditional oil seed crop widely cultivated in many countries. The top producers of sesame seeds are mainly Tanzania, Myanmar, India, China and Japan. Sesame oil contains high level of unsaturated fatty acids (80%) and low levels of saturated fatty acids (20%). The main fatty acids are palmitic, stearic, oleic, linoleic and trace amounts of linolenic fatty acids. Sesame seed contains 50–60% of high-quality oil rich in natural antioxidants such as sesamin, sesamolin, sesaminol and sesamol it enhances the stability and keeping quality of sesame oil. Sesame seeds have good sources of dietary fibre, fats, vitamins, minerals, proteins and rich in anti-oxidants. Polyunsaturated fatty acids in sesame will reduce the risk of high blood pressure, cardiac disorders and blood sugar levels. Sesame is believed to have been originated in India where maximum variability of genetic resources is available. High yielding varieties available to date have reached the yield plateau even with the advanced cultivation practices. The area under oilseed crops cultivation also reducing every year. Hence, there is an urgent need to increase the oil content and yield of Indian sesame varieties. Understanding the available germplasm and novel interventions to develop high yielding varieties warrant both molecular and phenotypic data which is meagre in case of sesame.