Micellization of three didodecyl dicationic dibromide gemini surfactants with different methylene spacer lengths, 12-s-12,2Br- where s = 3-5 groups, has been investigated in water-ethylene glycol, EG, mixtures weight percentages EG up to 50%. Subsequently, effects the addition organic solvent on micellar growth these and surfactant concentration range sphere-to-rod transitions occur were studied by means steady-state time-resolved fluorescence quenching spectroscopic measurements. Results...

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 the two pyrrolo[1,2‐ b ]isoxazole derivatives 13 and 14 . The major adduct was converted to 7‐deoxycasuarine 7 ), potent, specific, competitive inhibitor amyloglucosidase from Rhizopus mold (see Table ).

Novel pyrrolidine-based multivalent iminosugars, synthesized by a CuAAC approach, have shown remarkable effects towards jack bean α-mannosidase and Golgi from Drosophila melanogaster, as well good selectivity with respect to lysosomal α-mannosidase, which is important for anticancer applications. STD NMR molecular modeling studies supported mechanism specific interactions of the bioactive iminosugars Jack α-mannosidase. TEM suggested binding mode that involves formation aggregates, result...

Abstract A general strategy for the synthesis of diversely substituted 3,4,5‐trihydroxypiperidines (including two natural products), 5‐amino‐3,4‐dihydroxypiperidines, 3,4,5‐trihydroxypipecolic acids, and 2‐(aminomethyl)‐3,4,5‐trihydroxypiperidines is reported. The procedure used a double reductive amination or Strecker reaction, starting from differently protected aldehydes readily synthesized on gram scale D ‐mannose. biological activities target compounds were evaluated, some them showed...

As other monosaccharide mimics such as the azasugars and carbasugars (with nitrogen carbon atom, respectively, instead of oxygen atom in ring) thiosugars sulfur have gained importance glycobiology potential drugs. Biological properties monothiosaccharides are presented methods for their synthesis reviewed analyzed. Since report 5-thio-α-D-xylopyranose, first example ever described, forty years imaginative chemistry produced a large number analogs biological interest. The preparative chemists...

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 ammonia aldonic esters as key steps, are used. compounds were assayed for their inhibitory activity towards 13 commercially available glycosidases. Compounds that share the absolute configuration at C(2,3,4,5)...

Abstract The total synthesis of natural (+)‐hyacinthacine A 1 ( 6 ), (+)‐7a‐ epi ‐hyacinthacine 7 ) and their 6‐hydroxy analogues 21 16 was achieved using a nitrone cycloaddition strategy with D ‐ribose‐derived cyclic 8 as the dipole tert ‐butyl acrylate dipolarophile. After separation adducts, reductive cleavage N–O bond followed by lactam reduction deprotection afforded two non‐natural hydroxy in excellent yields. which required deoxygenation at C(6), accomplished DIBAL‐H mesylate...

Abstract The synthesis of three tetrahydroxyindolizidines and one tetrahydroxypyrrolizidine related to natural hyacinthacines B their biological evaluation as glycosidase inhibitors is reported. target molecules were obtained through highly stereoselective cycloadditions between sugriched allylic homoallylic alcohols. This allowed the installation a methyl group at C5 – common feature many with high control over stereoselectivity. new compounds inhibit amyloglucosidase from Aspergillus niger...

We have developed [2.2.1]azabicyclic vinyl sulfone reagents that simultaneously enable cysteine-selective protein modification and introduce a handle for further bioorthogonal ligation. The reaction is fast selective cysteine relative to other amino acids nucleophilic side-chains, the formed products are stable in human plasma moderately resistant retro Diels-Alder degradation reactions. A model biotinylated reagent was shown efficiently label two cysteine-tagged proteins, ubiquitin C2Am,...

Abstract The 1,3 dipolar cycloaddition reactions of three pentose‐derived pyrroline N ‐oxides with mono‐ and disubstituted alkenes are reported. A strong dependence the diastereoselectivity cycloadditions on relative configuration nitrone stereocentres was observed. Further transformation reaction products allowed synthesis four new tetrahydroxylated indolizidines. Their activity as glycosidase inhibitors evaluated against a panel commercially available glycosidases. specificity inhibitory...

Two libraries of mono- and dimeric pyrrolidine iminosugars were synthesized by CuAAC (thio)urea-bond-forming reactions from the respective azido/aminohexylpyrrolidine iminosugar precursors. The resulting monomeric compounds screened for inhibition β-N-acetylglucosaminidase Jack beans, plant ortholog human lysosomal hexosaminidases. A selection best inhibitors these was then evaluated against β-N-acetylhexosaminidase B (hHexB) nucleocytoplasmic (hOGA). This evaluation identified a potent (nM)...

A dynamic imine library formed in solution provides a fast route to drug discovery. Imine formation from diamine 4 and sublibrary of aldehydes can be used for the efficient discovery glycosidase inhibitors through new combinatorial approach. When equilibrium shown is reached rapidly under dilute conditions, mixture imines produced screened by glycosidase, which binds preferentially best inhibitor. Supporting information this article available on WWW http://www.chembiochem.com or author....

In this part other procedures of glycosylation reactions by direct activation are presented. We will focus on the n-pentenyl glycoside, O-alkylation and trichloroacetimidate methods. The use glycosyl phosphates glycals in glycosidation also discussed. Updated examples these methodologies involving total synthesis oligosaccharides related compounds considered. Keywords: glycosides, tetrasaccharide, Mycobacterial lipoarabinomannan, bioconjugation, Alkylation

Abstract To probe the utility of a multivalent approach for fucosidase inhibition, series di‐ and tri‐valent imino sugars based on L ‐fuco ‐configured 1,4‐imino‐ 1,4‐bis(imino)‐cyclitol epitopes has been synthesized analyzed inhibition with best trivalent species yielding modest improvement in binding constant. Structural analysis representative pair mono‐ performed bacterial fucosidase, Bt Fuc2970. The 3D structures show imino‐cyclitol 3 E conformation, consistent known pathway action.

The synthesis of the first multivalent pyrrolizidine iminosugars is reported. key azido intermediates 4 and 31 were prepared after suitable synthetic elaboration cycloadduct obtained from 1,3-dipolar cycloaddition D-arabinose derived nitrone to dimethylacrylamide. step strategy was stereoselective installation an moiety at C-6 skeleton. click reaction with different monovalent dendrimeric alkyne scaffolds allowed preparation a library new mono- compounds that preliminarily assayed as...

Abstract An azanorbornadiene bromovinyl sulfone reagent for cysteine‐selective bioconjugation has been developed. Subsequent reaction with dipyridyl tetrazine leads to bond cleavage and formation of a pyrrole‐linked conjugate. The latter involves ligation the azanorbornadiene‐tagged protein through inverse electron demand Diels–Alder cycloaddition subsequent double retro‐Diels–Alder reactions form stable pyrrole linkage. sequence site‐selective followed by bioorthogonal was efficiently...

Cancer cells are highly dependent on Nicotinamide phosphoribosyltransferase (NAMPT) activity for proliferation, therefore NAMPT represents an interesting target the development of anti-cancer drugs. Several compounds, such as FK866 and CHS828, were identified potent inhibitors with strong activity, although none them reached late stages clinical trials. We present herein preparation three libraries new containing (pyridin-3-yl)triazole, (pyridin-3-yl)thiourea (pyridin-3/4-yl)cyanoguanidine...

N-Phenylaminomethyl benzimidazolyl moieties attached at C-2 of (2S,3S,4R,5S)-5-methylpyrrolidine-3,4-diol increase the potency and selectivity inhibitory activity these systems towards α-L-fucosidases.

Efficient methodologies for the synthesis of regioisomeric 3-pyrrolines by reaction electron-deficient imines and sulfur-containing allenyl derivatives are presented. Lithiated thioallenes give 2-aryl-3-phenylsulfonyl-3-pyrrolines, whereas sulfones furnish isomeric 2-aryl-4-phenylsulfonyl-3-pyrrolines through migration sulfonyl group that catalyzes nucleophilic [3 + 2] cycloaddition.

A review dealing with the general aspects of oligosaccharide synthesis including recent advances in protecting group strategies and anomeric control for stereoselective glycosylations, focusing on formation 1,2-cis-glycosides, are presented. Recent examples intramolecular aglycon delivery approach remote effect stereochemistry new glycosidic bond considered. In this part, updated use glycosyl halides, thioglycosides, sulfoxides phenylselenides as glycosylating agents also discussed....

A review dealing with iminosugars as inhibitors of α-L-fucosidases is presented. The different synthetic approaches for the preparation most relevant ones well their inhibitory properties are Keywords: Azafagomines, hydroxylated azepanes, piperidines, pyrrolidines, fucosidase inhibitors, iminosugars, azasugars, L-Fucosidase Inhibitors, glycosylation, glycosylation reactions, hydrolysis, glycoconjugates, carcinomas, L-fucosidases, Thermotoga maritima, maritima enzyme, iminocyclitols,...