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We achieved synthesis of seven stereoisomers of 1- C-n- butyl-L-iminofuranose derivatives using catalytic asymmetric alkylation and Negishi coupling as key reactions. The synthetic strategy based on these key reactions was quite useful, since both α- and β-iminofuranoses could be obtained by switching the chirality of the ligand employed for the AAA reaction. The common intermediates for α- and β-isomers were subjected to further manipulations to install a diol unit at C2 and C3 to give the desired stereoisomers of L-iminofuranose derivatives. We achieved the preparation of all stereoisomers of 1- C-n- butyl-L-iminofuranose derivatives, with the exception of β-lyxo type iminofuranose. It is noteworthy that a synthetic route for many stereoisomers of iminofuranose derivatives was developed. Unfortunately, none of the L-iminofuranoses obtained showed inhibitory activity against the α-glycosidases examined—e.g., maltase, sucrase, and isomaltase. Image 1 [ABSTRACT FROM AUTHOR]

The iminosugar 2,5-dideoxy-2,5-imino- d -altritol (DIA, 2 ) is a powerful competitive inhibitor of α-galactosidase A and has shown much promise as a pharmacological chaperone for the treatment for Fabry disease. Notwithstanding, syntheses of DIA are in want of optimisation. Accordingly, we report on the total synthesis of DIA in 7 steps and in 22% overall yield from readily available d -tagatose. This is the shortest and most efficient synthesis of DIA to date, with key steps in our synthetic strategy including a diastereoselective reductive amination and an I 2 -mediated carbamate annulation. [ABSTRACT FROM AUTHOR]

Azanucleosides, sugar-modified nucleoside analogues containing a 4′ nitrogen atom, have shown a lot of therapeutic potential, e.g. as anti-cancer and antiviral agents. We report the synthesis of a series of 2’-homoazanucleosides, in which the nucleobase is attached to the 2’-position of the pyrrolidine ring via a methylene linker. A suitable orthogonally protected iminosugar was synthesized by ring closing metathesis and dihydroxylation as key steps and further converted to a series of 8 nucleoside analogues through Mitsunobu reaction with suitably protected nucleobases. The 5′ position of the adenine analogue was then further derivatized with thiols to afford 2 additional compounds. The final compounds were evaluated for biological activity. [ABSTRACT FROM AUTHOR]

Cu-catalysed ketenimine mediated multicomponent reaction led to an efficient installation of N -allyl N -sulfonyl amide functionality onto a sugar derived terminal alkyne via intramolecular 3,3 sigmatropic rearrangement of an initially formed N -sulfonyl imidate. This strategy is further extended to the application of hydrative amide synthesis on chiral alkynyl amines followed by in situ intramolecular transamidation which led to the development of a novel one-pot reaction for the construction of a δ -lactam iminosugar. [ABSTRACT FROM AUTHOR]

Abstract: A simple and efficient synthesis of 1,4-dideoxy-1,4-imino-d-ribitol, 1,4-dideoxy-1,4-imino-l-lyxitol, N-benzyl derivative of d-ribitol, 3,4,5-trihydroxy-piperidine, l-4-epi-isofagomine and d-3-epi-isofagomine, which are glycosidase inhibitors has been described from the commercially available d-ribose as a starting material. [Copyright &y& Elsevier]

Abstract: Synthesis and inhibitory activities against α-l-fucosidase of phenylalkyl-substituted polyhydroxypiperidines have been described. Among the newly synthesized compounds, 2,4,6-trichloro derivative (16q) showed very high inhibitory activity against α-l-fucosidase with IC50 value of 0.005 μM, and K i values of 0.0011 μM, respectively. [Copyright &y& Elsevier]

Abstract: We describe herein the synthesis of glyconamides and glycosylamines using molecular iodine on benzylated carbohydrates. During the improvement and the optimization of the direct oxidative amidation reaction, we also discovered the possibility to form glycosylamines with excellent yields and short reaction times in comparison with the previously reported procedures. Advantages of these methods are the operational simplicity, elimination of use of complicated reagents and procedures, and generality of the reactions. Our methodology is an excellent access to precursors of N-alkyliminosugars and imino-C-glycosides. [Copyright &y& Elsevier]

Abstract: Diversity-oriented synthesis of derivatives of the potent glycosidase inhibitor lentiginosine can be achieved in an efficient and versatile way by two modular approaches on key intermediates. After assembling the indolizidine ring system through 1,3-dipolar cycloaddition of a dihydroxylated pyrroline N-oxide with 4-butenol followed by elaboration of the isoxazolidine moiety, the 7-amino and 7-azido derivatives synthesized can be conjugated with functionalised chains by coupling, respectively, with an amino acid, or an alkyne in copper-catalyzed Huisgen cycloadditions. [Copyright &y& Elsevier]

Abstract: High yielding synthesis of six- and five-membered N-substituted iminosugar glycosides and of five-membered iminosugar thioglycosides by nucleophilic opening of both new and previously described N-diethoxycarbonylvinyl anhydroiminosugar derivatives (glycosyl donors) with primary alcohols, primary thiols, and thiophenol (glycosyl acceptors) is reported. The reactions are highly stereoselective, with anomeric ratios better than 4:1. [ABSTRACT FROM AUTHOR]

Abstract: A series of 4,4-difluoroisofagomine analogues were synthesized. These compounds were tested for inhibition of eight glycosidases. The 3R,5R isomer 1 is a new and potent inhibitor against β-glucosidase from almonds with K i value of 1.2μM. The influence of the gem-difluoromethylene group (CF2) on binding to glycosidases is discussed. It is concluded that only non-essential hydroxyl groups can be replaced by the gem-difluoro group and that in such a case (β-glycosidase) the change in inhibition is, interestingly, a result of the change in base strength. [Copyright &y& Elsevier]

Abstract: Glycoside trimming enzymes are crucially important in a broad range of metabolic pathways, including glycoprotein and glycolipid processing and carbohydrate digestion in the intestinal tract. Amongst the large array of enzymes, glucosidases are postulated to be a powerful therapeutic target since they catalyze the cleavage of glycosidic bonds releasing glucose from the non-reducing end of an oligo- or polysaccharide chain involved in glycoprotein biosynthesis. Glucosidase inhibitors are currently of interest owing to their promising therapeutic potential in the treatment of disorders such as diabetes, human immunodeficiency virus (HIV) infection, metastatic cancer, and lysosomal storage diseases. Glucosidase inhibitors have also been useful in probing biochemical pathways and understanding structure–activity relationship patterns required for mimicking the enzyme transition state. Amongst the various types of glucosidase inhibitors, disaccharides, iminosugars, carbasugars, thiosugars, and non-sugar derivatives have received great attention. This review is aimed at highlighting the main chemical classes of glucosidase inhibitors, as well as their biological activities toward α- and β-glucosidases, but it is not intended to be an exhaustive review on the subject. Inhibition data on the compounds covered in this review are included in a tabular form as an Appendix, where the type of each glucosidase associated with a specific inhibitor is also given. [Copyright &y& Elsevier]

Synthetic routes to peptidomimetic compounds derived from saccharide scaffolds are described. The regioselective introduction of pivaloyl groups was achieved from N-benzyloxycarbonyl protected 1-deoxymannojirimycin or via d-fructopyranosides. The results from biological evaluation of the saccharide derivatives as HIV-protease inhibitors are included. [Copyright &y& Elsevier]