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ABSTRACT: The high strain of bicyclic systems drives retro-condensation reactions on bridgehead substituted bicyclo[2.2.1]hept-2-enes giving rise to orthogonally functionalized cyclopentene, 2,5-dihydrofuran, and 3-pyrroline scaffolds. Retro-Dieckman reactions were easily carried out on 3-tosyl-(7-carba/7-oxa/7-aza)bicyclo[2.2.1]hept-5-en-2-ones. Retro-aldol reactions of N-Boc-3-tosyl-7-azabicyclo[2.2.1]hept-5-en-2-ol and functionalized N-Boc-3-tosyl-7-azabicyclo[2.2.1]heptan-2-ols yield functionalized pyrrolidine scaffolds stereoselectively. The same reaction does not work with corresponding norbornene and 7-oxanorbornene derivatives.
Organic Letters 11/2011; 13(23):6244-7. · 5.86 Impact Factor
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ABSTRACT: A review dealing with iminosugars as inhibitors of α-L-fucosidases is presented. The different synthetic approaches for the preparation of the most relevant ones as well as their inhibitory properties are presented.
Current Organic Synthesis 01/2011; 8(1):102-133. · 3.43 Impact Factor
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ABSTRACT: A review dealing with 1,4-iminoalditol (hydroxylated pyrrolidine) derivatives as inhibitors of α-L-fucosidases including the different synthetic approaches for their preparation as well as their inhibitory properties is presented.
CHIMIA International Journal for Chemistry 01/2011; 65(1):40-44. · 1.21 Impact Factor
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ABSTRACT: Since the discovery of the 'formose reaction' by Butlerow,[1] total synthesis of carbohydrates has undergone rapid development. The most important methods for the asymmetric synthesis of monosaccharides and analogues of biological importance are presented. Nowadays any natural and non-natural monosaccharide can be prepared pure in both enantiomeric forms starting from inexpensive starting materials. Metal-based asymmetric catalysis and organocatalysis have been successfully applied, alone or in combination with chemoenzymatic methods. Alternative methods rely upon substrate- or reagent- controlled diastereo- and enantioselective reactions. Suitably protected carbohydrates have been prepared by total synthesis, thus allowing their direct use in the preparation of oligosaccharides and analogues.[2]
CHIMIA International Journal for Chemistry 01/2011; 65(1):85-90. · 1.21 Impact Factor
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ABSTRACT: We present herein a selection of ingenious methods that have been developed to convert inexpensive furan, pyrrole and unsaturated hydrocarbons into enantiomerically enriched monosaccharides and analogues of biological interest.
CHIMIA International Journal for Chemistry 01/2011; 65(1-2):91-6. · 1.21 Impact Factor
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ABSTRACT: A review dealing with 1,4-iminoalditol (hydroxylated pyrrolidine) derivatives as inhibitors of alpha-L-fucosidases including the different synthetic approaches for their preparation as well as their inhibitory properties is presented.
CHIMIA International Journal for Chemistry 01/2011; 65(1-2):40-4. · 1.21 Impact Factor
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ABSTRACT: The synthesis of a novel aminomethyl C-3 substituted L-fuco-azafagomine and of its C-6 epimer from D-lyxose is reported. The key step of the synthesis is the introduction of the biimino (-NH-NH-) moiety by reductive hydrazination of a 1-deoxy-ketohexose with tert-butyl carbazate. The 3-aminomethyl-azafagomine derivatives were used as lead compounds in the generation of libraries of novel types of derivatives by attaching different hydrophobic groups on the aminomethyl substituent through amide linkages. These polyhydroxylated hexahydropyridazines can be viewed as a new type of diaza-C-glycoside analogues having a biimino (-NH-NH-) moiety. The conformational analysis and the glycosidase inhibitory properties of all the new C-3 substituted azafagomines synthesized are also reported. Those having L-fuco configuration have shown a selective inhibition of α-L-fucosidases.
Bioorganic & medicinal chemistry 07/2010; 18(13):4648-60. · 2.82 Impact Factor
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ABSTRACT: The synthesis of 3-substituted L-fuco-azafagomines from D-lyxose is reported. They represent the first example of aza-C-glycosides having a biimino (-NH-NH-) moiety. The key step of the synthesis is the introduction of the hydrazine moiety by reductive hydrazination of a 1-deoxy-ketohexose with tert-butyl carbazate. Their glycosidase inhibitory properties are also reported.
Synlett 01/2010; · 2.71 Impact Factor
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ABSTRACT: Efficient methodologies for the synthesis of regioisomeric 3-pyrrolines by reaction of electron-deficient imines and sulfur-containing allenyl derivatives are presented. Lithiated thioallenes give 2-aryl-3-phenylsulfonyl-3-pyrrolines, whereas allenyl sulfones furnish the isomeric 2-aryl-4-phenylsulfonyl-3-pyrrolines through migration of the sulfonyl group that catalyzes the nucleophilic [3 + 2] cycloaddition.
Organic Letters 10/2009; 11(21):4778-81. · 5.86 Impact Factor
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ABSTRACT: The stereoselective synthesis of new 3,4-dihydroxypyrrolidine derivatives starting from D-mannose, D-ribose and L-fucose is presented. Two synthetic strategies employing organometallic addition to hemiacetalic sugars followed by selective nucleophilic displacement or conjugate addition of ammonia to conjugate aldonic esters as key steps, are used. The new compounds were assayed for their inhibitory activity towards 13 commercially available glycosidases. Compounds that share the absolute configuration at C(2,3,4,5) of L-fucopyranosides and incorporate aromatic moieties are potent and selective inhibitors of alpha-L-fucosidases in the nM range.
Organic & Biomolecular Chemistry 04/2009; 7(6):1192-202. · 3.70 Impact Factor
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ABSTRACT: In this part other procedures of glycosylation reactions by direct activation are presented. We will focus on the n-pentenyl glycoside, the O-alkylation and the trichloroacetimidate methods. The use of glycosyl phosphates and glycals in glycosidation reactions are also discussed. Updated examples of these glycosylation methodologies involving total synthesis of oligosaccharides and related compounds are considered.
Current Organic Synthesis 04/2008; 5(2):81-116. · 3.43 Impact Factor
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Annalen der Chemie und Pharmacie 04/2008; 2008(17):2973 - 2982. · 3.10 Impact Factor
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ABSTRACT: A review dealing with the general aspects of oligosaccharide synthesis including the recent advances in protecting group strategies and anomeric control for stereoselective glycosylations, focusing on the formation of 1,2-cis-glycosides, are presented. Recent examples of the intramolecular aglycon delivery approach and of the remote effect on the stereochemistry of the new glycosidic bond are considered. In this part, updated examples of the use of glycosyl halides, thioglycosides, sulfoxides and phenylselenides as glycosylating agents for oligosaccharide synthesis are also discussed.
Current Organic Synthesis 01/2008; 5(1):33-60. · 3.43 Impact Factor
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ABSTRACT: Nine homotrifunctional cross-linking reagents are presented. Their synthesis and chemical properties as well as their characterization by classical mechanical conformational searching techniques is reported. Mixed Low Mode and Monte Carlo searching techniques were used to exhaustively sample the OPLS2005/GBSA(water) potential energy surface of trisubstituted cyclohexane and benzene derivatives of C3 symmetry. Geometric structure, molecular length, and hydrogen-bonding patterns were analyzed. Nonaromatic compounds exhibited exclusively chair conformations at low energies, with a preference for axial or equatorial arms depending upon the presence of additional ring substituent Me groups. Increasing chain length often resulted in overall shorter molecular length due to additional chain flexibility. These results were consistent with one- and two-dimensional temperature-dependent NMR studies.
The Journal of Organic Chemistry 09/2007; 72(18):6776-85. · 4.45 Impact Factor
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ABSTRACT: A series of trivalent CD4-mimetic miniproteins was synthesized, in which three CD4M9 miniprotein moieties were tethered on a threefold-symmetric scaffold. The trivalent miniproteins were designed to target the CD4-binding sites displayed in the trimeric gp120 complex of HIV-1. The synthesis takes advantage of the highly efficient ligation between a cysteine-tagged CD4M9 miniprotein and a suitable trivalent maleimide that varied in the nature and length of spacer. Antiviral assay revealed that most of the synthetic trivalent miniproteins demonstrated significantly enhanced anti-HIV activities over the monomeric CD4M9 against both R5- and X4-tropic viruses, indicating the beneficial multivalent effects. One compound that possesses a hydrophobic linker was shown to be 140-fold more active than CD4M9 against HIV-1(Bal) infection, implicating a positive contribution of the lipid portion to the antiviral activity. It was also found that most of the trivalent miniproteins showed comparable anti-HIV activities in comparison with a typical bivalent miniprotein, regardless of the length of the linker. The results implicate a novel mechanism of the interactions between the multivalent inhibitors and the trimeric gp120 complex.
Bioorganic & Medicinal Chemistry 07/2007; 15(12):4220-8. · 2.92 Impact Factor
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Annalen der Chemie und Pharmacie 02/2006; 2006(8):1876 - 1885. · 3.10 Impact Factor
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ABSTRACT: N-Phenylaminomethyl benzimidazolyl moieties attached at C-2 of (2S,3S,4R,5S)-5-methylpyrrolidine-3,4-diol increase the potency and selectivity of the inhibitory activity of these systems towards alpha-L-fucosidases.
Chemical Communications 11/2005; · 6.17 Impact Factor
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ABSTRACT: A few alpha-L-fucosidase inhibitors and alpha-D-glucosidase inhibitors have shown in vitro anti-HIV activities, that have been attributed to their ability to inhibit HIV entry. The mechanism of action of inhibitors such as 1-deoxynojirimycin (1) is not clearly established. One possible hypothesis is that the glycosidase inhibition affects the final conformation of the glycoproteins involved in the virus/cell recognition and fusion phenomena. This hypothesis is presented critically and the mechanisms of some glycoprotein biosynthesis are out-lined. Up to now, very few glycosidase inhibitors have been assayed for their potential as HIV entry inhibitors. Further assaying should be done and larger collections of glycosidase inhibitors should be prepared. To help investigations in that perspective, the inhibitory activities of alpha-glucosidase and alpha-L-fucosidase inhibitors have been summarized.
Current Drug Metabolism 09/2004; 5(4):329-61. · 5.11 Impact Factor
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ABSTRACT: Several 2-(aminomethyl)-and 2-(2-aminoethyl)-pyrrolidine-3,4-diol derivatives have been assayed for their inhibitory activities towards glycosidases. Good inhibitors of alpha-mannosidases must have the (2R,3R,4S) configuration and possess 2-(benzylamino)methyl substituents. Stereomers with the (2S,3R,4S) configuration are also competitive inhibitors of alpha-mannosidases, but less potent as they share the configuration of C(1), C(2), C(3) of beta-D-mannosides rather than that of alpha-D-mannosides. Interestingly, (2S,3R,4S)-2-[2-[(4-phenyl)phenylamino]ethyl]pyrrolidine-3,4-diol (12g) inhibits several enzymes, for instance alpha-L-fucosidase from bovine epididymis (K(i)=6.5microM, competitive), alpha-galactosidase from bovine liver (K(i)=5microM, mixed) and alpha-mannosidase from jack bean (K(i)=102microM, mixed). Diamines such as (2R,3S,4R)-2-[2-(phenylamino) or 2-(benzylamino)ethyl]pyrrolidine-3,4-diol (ent-12a, ent-12b) inhibit beta-glucosidase from almonds (K(i)=13-40microM, competitive).
Bioorganic & Medicinal Chemistry 12/2003; 11(23):4897-911. · 2.92 Impact Factor
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ABSTRACT: Reaction of 1,4-anhydro-2,3,5-tri-O-benzyl-1-deoxy-1-imino-D-arabinitol N-oxide (8) with allyl alcohol produced a 3.6 : 1 mixture of the two pyrrolo[1,2-b]isoxazole derivatives 13 and 14. The major adduct 13 was converted to 7-deoxycasuarine (7), a potent, specific, and competitive inhibitor of amyloglucosidase from Rhizopus mold (see Table).
Helvetica Chimica Acta 08/2003; 86(9):3066 - 3073. · 1.48 Impact Factor
