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Mario B Pinto - One of the best experts on this subject based on the ideXlab platform.
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studies directed toward the stereochemical structure determination of the naturally occurring glucosidase inhibitor kotalanol synthesis and inhibitory activities against human maltase glucoamylase of seven carbon chain extended homologues of salacino
2008Co-Authors: Ravindranath Nasi, David R Rose, Brian O Patrick, Mario B PintoAbstract:The synthesis of new seven-carbon, chain-extended sulfonium salts of 1,4-anhydro-4-thio-d-Arabinitol, analogues of the naturally occurring glycosidase inhibitor salacinol, are described. These compounds were designed on the basis of the structure activity data of chain-extended analogues of salacinol, with the intention of determining the hitherto unknown stereochemical structure of kotalanol, the naturally occurring seven-carbon chain-extended analogue of salacinol. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the PMB-protected 1,4-anhydro-4-thio-d-Arabinitols at the least hindered carbon atom of two 1,3-cyclic sulfates differing in stereochemistry at only one stereogenic center. The desired cyclic sulfates were synthesized starting from d-glucose via Wittig olefination and Sharpless asymmetric dihydroxylation. Deprotection of the coupled products by using a two-step sequence afforded two sulfonium sulfates. Optical rotation data for one of our compounds indicated...
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studies directed toward the stereochemical structure determination of the naturally occurring glucosidase inhibitor kotalanol synthesis and inhibitory activities against human maltase glucoamylase of seven carbon chain extended homologues of salacinol
2008Co-Authors: Ravindranath Nasi, David R Rose, Brian O Patrick, Lyann Sim, Mario B PintoAbstract:The synthesis of new seven-carbon, chain-extended sulfonium salts of 1,4-anhydro-4-thio- d-Arabinitol, analogues of the naturally occurring glycosidase inhibitor salacinol, are described. These compounds were designed on the basis of the structure activity data of chain-extended analogues of salacinol, with the intention of determining the hitherto unknown stereochemical structure of kotalanol, the naturally occurring seven-carbon chain-extended analogue of salacinol. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the PMB-protected 1,4-anhydro-4-thio- d-Arabinitols at the least hindered carbon atom of two 1,3-cyclic sulfates differing in stereochemistry at only one stereogenic center. The desired cyclic sulfates were synthesized starting from d-glucose via Wittig olefination and Sharpless asymmetric dihydroxylation. Deprotection of the coupled products by using a two-step sequence afforded two sulfonium sulfates. Optical rotation data for one of our compounds indicated a correspondence with that reported for kotalanol. However, comparison of (1)H and (13)C NMR spectral data of the synthetic compounds with those of kotalanol indicated discrepancies. The collective data from this and published work were used to propose a tentative structure for the naturally occurring compound, kotalanol. Comparison of physical data of previously synthesized analogues with those for the recently isolated six-carbon chain analogue, ponkoranol or reticulanol, also led to elucidation of this structure. Interestingly, both our compounds inhibited recombinant human maltase glucoamylase (MGA), as expected from our previous structure activity studies of lower homologues, with K i values of 0.13 +/- 0.02 and 0.10 +/- 0.02 microM.
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synthesis of 2 amido 2 amino and 2 azido derivatives of the nitrogen analogue of the naturally occurring glycosidase inhibitor salacinol and their inhibitory activities against o glcnacase and nagz enzymes
2008Co-Authors: Niloufar Choubdar, Ramakrishna G Bhat, Keith A Stubbs, Scott A Yuzwa, Mario B PintoAbstract:Seven 2-substituted derivatives of the nitrogen analogue of salacinol, a naturally occurring glycosidase inhibitor, were synthesized for structure-activity studies with hexosaminidase enzymes. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the 2-azido-1,4-dideoxy-1,4-imino-D-Arabinitol at the least hindered carbon atom of 2,4-O-benzylidene-L-erythritol-1,3-cyclic sulfate. Hydrogenation of the azido zwitterionic compound in methanol resulted in the reduction of the azide and subsequent methylation of the resulting amine in one pot. A similar reaction, with ethanol as the solvent, gave the N-ethyl derivative. The 2-amino analogues were finally obtained by the reduction of the azide function using triphenylphosphine. Acylation of the amine using acetic, propionic, or valeric anhydride afforded the corresponding 2-amido derivatives. Deprotection of the acylated, coupled products using 80% trifluoroacetic acid proceeded smoothly. Unlike their sulfonium ion counterparts, these compounds were stable and did not undergo ring opening. We also report the synthesis of the parent nitrogen heterocycles, N-Boc-1,2,4-trideoxy-2-amino-1,4-imino-D-Arabinitol, and 1,2,4-trideoxy-2-acetamido-1,4-imino-D-Arabinitol and its corresponding N-Boc protected compound. The 2-substituted analogues and the parent iminoalditol showed marginal activity (<33% at 250 microM) against human O-GlcNAcase and Vibrio cholerae NagZ enzymes.
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synthesis of phosphate derivatives related to the glycosidase inhibitor salacinol
2007Co-Authors: Ramakrishna G Bhat, Nag S. Kumar, Mario B PintoAbstract:Abstract The syntheses of polyhydroxylated imino- and anhydro thio-alditol compounds related to the naturally occurring glycosidase inhibitor, salacinol, containing a phosphate group in the side chain are described. The compounds lack hydroxyl groups on the acyclic side chain and are prototypes of the exact salacinol analogue. The synthetic strategy relies on the Mitsunobu reaction of N- and S-hydroxyalkyl derivatives of 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino- d -Arabinitol and 1,4-anhydro-2,3,5-tri-O-benzyl-1-thio- d -Arabinitol with dibenzyl phosphate to yield the corresponding protected heteroalditol phosphates. Screening of these compounds against recombinant human maltase glucoamylase (MGA), a critical intestinal glucosidase involved in the processing of oligosaccharides of glucose into glucose itself, shows that they are not effective inhibitors of MGA and demonstrates the importance of the hydroxyl and/or sulfate substituents present on the side chain for effective inhibition. The attempted synthesis of the exact analogue of salacinol by opening of cyclic phosphates is also described.
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synthesis of analogues of salacinol containing a carboxylate inner salt and their inhibitory activities against human maltase glucoamylase
2007Co-Authors: Wang Chen, David R Rose, Mario B PintoAbstract:Abstract The syntheses of analogues of the naturally occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt are described. Salacinol is a sulfonium ion with an internal sulfate counterion. The synthetic strategy relies on the nucleophilic attack of 1,4-anhydro-2,3,5-tri- O -benzyl-4-thio- d - or l -Arabinitol at the least hindered carbon of 4,5-anhydro-2,3- O -isopropylidene- d -ribonic acid benzyl ester to yield coupled adducts. Deprotection of the coupled products gives the target compounds. The compound derived from d -Arabinitol inhibits recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with a K i value of 10 ± 1 μM.
David R Rose - One of the best experts on this subject based on the ideXlab platform.
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studies directed toward the stereochemical structure determination of the naturally occurring glucosidase inhibitor kotalanol synthesis and inhibitory activities against human maltase glucoamylase of seven carbon chain extended homologues of salacinol
2008Co-Authors: Ravindranath Nasi, David R Rose, Brian O Patrick, Lyann Sim, Mario B PintoAbstract:The synthesis of new seven-carbon, chain-extended sulfonium salts of 1,4-anhydro-4-thio- d-Arabinitol, analogues of the naturally occurring glycosidase inhibitor salacinol, are described. These compounds were designed on the basis of the structure activity data of chain-extended analogues of salacinol, with the intention of determining the hitherto unknown stereochemical structure of kotalanol, the naturally occurring seven-carbon chain-extended analogue of salacinol. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the PMB-protected 1,4-anhydro-4-thio- d-Arabinitols at the least hindered carbon atom of two 1,3-cyclic sulfates differing in stereochemistry at only one stereogenic center. The desired cyclic sulfates were synthesized starting from d-glucose via Wittig olefination and Sharpless asymmetric dihydroxylation. Deprotection of the coupled products by using a two-step sequence afforded two sulfonium sulfates. Optical rotation data for one of our compounds indicated a correspondence with that reported for kotalanol. However, comparison of (1)H and (13)C NMR spectral data of the synthetic compounds with those of kotalanol indicated discrepancies. The collective data from this and published work were used to propose a tentative structure for the naturally occurring compound, kotalanol. Comparison of physical data of previously synthesized analogues with those for the recently isolated six-carbon chain analogue, ponkoranol or reticulanol, also led to elucidation of this structure. Interestingly, both our compounds inhibited recombinant human maltase glucoamylase (MGA), as expected from our previous structure activity studies of lower homologues, with K i values of 0.13 +/- 0.02 and 0.10 +/- 0.02 microM.
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studies directed toward the stereochemical structure determination of the naturally occurring glucosidase inhibitor kotalanol synthesis and inhibitory activities against human maltase glucoamylase of seven carbon chain extended homologues of salacino
2008Co-Authors: Ravindranath Nasi, David R Rose, Brian O Patrick, Mario B PintoAbstract:The synthesis of new seven-carbon, chain-extended sulfonium salts of 1,4-anhydro-4-thio-d-Arabinitol, analogues of the naturally occurring glycosidase inhibitor salacinol, are described. These compounds were designed on the basis of the structure activity data of chain-extended analogues of salacinol, with the intention of determining the hitherto unknown stereochemical structure of kotalanol, the naturally occurring seven-carbon chain-extended analogue of salacinol. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the PMB-protected 1,4-anhydro-4-thio-d-Arabinitols at the least hindered carbon atom of two 1,3-cyclic sulfates differing in stereochemistry at only one stereogenic center. The desired cyclic sulfates were synthesized starting from d-glucose via Wittig olefination and Sharpless asymmetric dihydroxylation. Deprotection of the coupled products by using a two-step sequence afforded two sulfonium sulfates. Optical rotation data for one of our compounds indicated...
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synthesis of analogues of salacinol containing a carboxylate inner salt and their inhibitory activities against human maltase glucoamylase
2007Co-Authors: Wang Chen, David R Rose, Mario B PintoAbstract:Abstract The syntheses of analogues of the naturally occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt are described. Salacinol is a sulfonium ion with an internal sulfate counterion. The synthetic strategy relies on the nucleophilic attack of 1,4-anhydro-2,3,5-tri- O -benzyl-4-thio- d - or l -Arabinitol at the least hindered carbon of 4,5-anhydro-2,3- O -isopropylidene- d -ribonic acid benzyl ester to yield coupled adducts. Deprotection of the coupled products gives the target compounds. The compound derived from d -Arabinitol inhibits recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with a K i value of 10 ± 1 μM.
Ao Fan - One of the best experts on this subject based on the ideXlab platform.
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green synthesis of 1 5 dideoxy 1 5 imino ribitol and 1 5 dideoxy 1 5 imino dl Arabinitol from natural d sugars over au al2o3 and so42 al2o3 catalysts
2021Co-Authors: Hongjian Gao, Ao FanAbstract:A green synthetic route for the synthesis of some potential enzyme active hydroxypiperidine iminosugars including 1,5-dideoxy-1,5-imino-ribitol and 1,5-dideoxy-1,5-imino-DL-Arabinitol, starting from commercially available D-ribose and D-lyxose was tested out. Heterogeneous catalysts including Au/Al2O3, SO42-/Al2O3 as well as environmentally friendly reagents were employed into several critical reaction of the route. The synthetic route resulted in good overall yields of 1,5-dideoxy-1,5-imino-ribitol of 54%, 1,5-dideoxy-1,5-imino-D-Arabinitol of 48% and 1,5-dideoxy-1,5-imino-L-Arabinitol of 46%. The Au/Al2O3 catalyst can be easily recovered from the reaction mixture and reused with no loss of activity.
Ravindranath Nasi - One of the best experts on this subject based on the ideXlab platform.
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studies directed toward the stereochemical structure determination of the naturally occurring glucosidase inhibitor kotalanol synthesis and inhibitory activities against human maltase glucoamylase of seven carbon chain extended homologues of salacino
2008Co-Authors: Ravindranath Nasi, David R Rose, Brian O Patrick, Mario B PintoAbstract:The synthesis of new seven-carbon, chain-extended sulfonium salts of 1,4-anhydro-4-thio-d-Arabinitol, analogues of the naturally occurring glycosidase inhibitor salacinol, are described. These compounds were designed on the basis of the structure activity data of chain-extended analogues of salacinol, with the intention of determining the hitherto unknown stereochemical structure of kotalanol, the naturally occurring seven-carbon chain-extended analogue of salacinol. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the PMB-protected 1,4-anhydro-4-thio-d-Arabinitols at the least hindered carbon atom of two 1,3-cyclic sulfates differing in stereochemistry at only one stereogenic center. The desired cyclic sulfates were synthesized starting from d-glucose via Wittig olefination and Sharpless asymmetric dihydroxylation. Deprotection of the coupled products by using a two-step sequence afforded two sulfonium sulfates. Optical rotation data for one of our compounds indicated...
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studies directed toward the stereochemical structure determination of the naturally occurring glucosidase inhibitor kotalanol synthesis and inhibitory activities against human maltase glucoamylase of seven carbon chain extended homologues of salacinol
2008Co-Authors: Ravindranath Nasi, David R Rose, Brian O Patrick, Lyann Sim, Mario B PintoAbstract:The synthesis of new seven-carbon, chain-extended sulfonium salts of 1,4-anhydro-4-thio- d-Arabinitol, analogues of the naturally occurring glycosidase inhibitor salacinol, are described. These compounds were designed on the basis of the structure activity data of chain-extended analogues of salacinol, with the intention of determining the hitherto unknown stereochemical structure of kotalanol, the naturally occurring seven-carbon chain-extended analogue of salacinol. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the PMB-protected 1,4-anhydro-4-thio- d-Arabinitols at the least hindered carbon atom of two 1,3-cyclic sulfates differing in stereochemistry at only one stereogenic center. The desired cyclic sulfates were synthesized starting from d-glucose via Wittig olefination and Sharpless asymmetric dihydroxylation. Deprotection of the coupled products by using a two-step sequence afforded two sulfonium sulfates. Optical rotation data for one of our compounds indicated a correspondence with that reported for kotalanol. However, comparison of (1)H and (13)C NMR spectral data of the synthetic compounds with those of kotalanol indicated discrepancies. The collective data from this and published work were used to propose a tentative structure for the naturally occurring compound, kotalanol. Comparison of physical data of previously synthesized analogues with those for the recently isolated six-carbon chain analogue, ponkoranol or reticulanol, also led to elucidation of this structure. Interestingly, both our compounds inhibited recombinant human maltase glucoamylase (MGA), as expected from our previous structure activity studies of lower homologues, with K i values of 0.13 +/- 0.02 and 0.10 +/- 0.02 microM.
George W J Fleet - One of the best experts on this subject based on the ideXlab platform.
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1 de oxy d Arabinitol
2008Co-Authors: Sarah F Jenkinson, George W J Fleet, Filipa P Da Cruz, Kathrine V Booth, Ken Izumori, David J WatkinAbstract:Addition of methyl lithium to d-erythrono-1,4-lactone followed by acid deprotection was shown, by X-ray crystallography, to give 1-deoxy-d-Arabinitol, C5H12O4, rather than 1-deoxy-d-ribitol as the major product. The crystal structure exists as hydrogen-bonded chains of molecules running parallel to the c axis which are further linked together by hydrogen bonds. Each molecule is a donor and an acceptor for four hydrogen bonds.
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efficient synthesis from d lyxonolactone of 2 acetamido 1 4 imino 1 2 4 trideoxy l Arabinitol labnac a potent pyrrolidine inhibitor of hexosaminidases
2007Co-Authors: J Shane S Rountree, Robert J Nash, Terry D Butters, Mark R Wormald, Raymond A Dwek, Naoki Asano, Kyoko Ikeda, Emma L Evinson, George W J FleetAbstract:The synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-Arabinitol LABNAc proceeded in an overall yield of 25%; the enantiomer, 2-acetamido-1,4-imino-1,2,4-trideoxy-d-Arabinitol DABNAc, was prepared from l-lyxonolactone. LABNAc and N-benzyl LABNAc are potent non-competitive inhibitors of d-hexosaminidase, whereas N-benzyl DABNAc exhibits weak competitive inhibition of the enzyme; this provides further evidence in support of Asano’s hypothesis that while d-imino sugar mimics inhibit d-glycohydrolases competitively, their l-enantiomers show non-competitive inhibition and in the case of iminofuranoses l-enantiomers are usually more potent inhibitors.
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synthesis from d lyxonolactone of 1 4 dideoxy 1 4 imino l Arabinitol a glucosidase inhibitor with in vitro anti viral activity
1993Co-Authors: James R Behling, Arthur Lee Campbell, Kevin A Babiak, John Medic, Payman Farid, George W J FleetAbstract:Abstract Benzylidenation is the only protection required in a 7 step synthesis of the hydrochloride of 1,4-dideoxy-1,4-imino-L-Arabinitol from D-lxyonolactone in an overall yield of 21%.