- Synthesis and glycosidase inhibition of: N-substituted derivatives of 1,4-dideoxy-1,4-imino-d-mannitol (DIM)
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N-Substituted derivatives of 1,4-dideoxy-1,4-imino-d-mannitol (DIM), the pyrrolidine core of swainsonine, have been synthesized efficiently and stereoselectively from d-mannose with 2,3:5,6-di-O-isopropylidene DIM (10) as a key intermediate. These N-substituted derivatives include N-alkylated, N-alkenylated, N-hydroxyalkylated and N-aralkylated DIMs with the carbon number of the alkyl chain ranging from one to nine. The obtained 33 N-substituted DIM derivatives were assayed against various glycosidases, which allowed a systematic evaluation of their glycosidase inhibition profiles. Though N-substitution of DIM decreased their α-mannosidase inhibitory activities, some of the derivatives showed significant inhibition of other glycosidases.
- Yang, Lin-Feng,Shimadate, Yuna,Kato, Atsushi,Li, Yi-Xian,Jia, Yue-Mei,Fleet, George W. J.,Yu, Chu-Yi
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p. 999 - 1011
(2020/02/15)
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- Chemistry of epoxysulfones: A new route to polyhydroxylated pyrrolidines
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A new methodology for the synthesis of polyhydroxylated pyrrolidines using epoxysulfones is described. The synthesis of two natural glycosidase inhibitors, 1,4-dideoxy-1,4-imino-D-lyxitol and 1,4-dideoxy-1,4-imino-D-mannitol (DIM), is reported.
- Diez, David,Beneitez, M. Templo,Gil,Moro,Marcos, Isidro S.,Garrido,Basabe,Urones, Julio G.
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p. 565 - 568
(2007/10/03)
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- Efficient stereodivergent synthesis of 1,4-dideoxy-1,4-iminohexitols from an (S)-glyceraldimine
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A stereodivergent synthesis of 1,4-dideoxy-1,4-imino-D-mannitol I and D-allitol III from an (S)-glyceraldimine, which is easily prepared from D-mannitol, has been achieved with overall yields of 62% and 49%, respectively. The synthesis is based on the add
- Badorrey, Ramón,Cativiela, Carlos,Díaz-De-Villegas, María D.,Díez, Roberto,Gálvez, José A.
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p. 719 - 722
(2007/10/03)
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- Synthesis of iminopolyols via Henry reaction: A short route to the α-mannosidase inhibitor 1,4-dideoxy-1,4-imino-D-mannitol and to amino analogues
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The α-mannosidase inhibitor 1,4-dideoxy-1,4-imino-D-mannitol (DIM) as well as amino analogues of DIM and of deoxy-manno-nojirimycin, respectively, have been prepared using a diastereoselective nitroaldol addition as the key step.
- Kiess, Frank-Michael,Poggendorf, Philip,Picasso, Sylviane,Jaeger, Volker
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p. 119 - 120
(2007/10/03)
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- Enantiospecific and stereoselective synthesis of polyhydroxylated pyrrolidines and indolizidines from trans-4-hydroxy-L-proline
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We have developed a short, efficient, and stereoselective synthesis of polyhydroxylated pyrrolidine and indolizidine glycosidase inhibitors starting from 4-hydroxy-L-proline. The regio- and stereoselective hydroxylation of an N-Pf-4-oxoproline enolate and the stereoselective reduction of the resulting keto alcohol allowed us to introduce the cis diol present in the target compounds. The different side chains needed to complete the syntheses of the target compounds were introduced by reduction of the ester group of a substituted proline or by reaction of organolithium or organomagnesium reagents with the same group followed by stereoselective reduction of the resulting ketones. Hydrogenolysis of the alcohols thus obtained gave the hydrochlorides of the desired pyrrolidine glycosidase inhibitors, which were obtained in nine steps in overall yields greater than 50%. The indolizidine glycosidase inhibitor 8-epi-swainsonine was also prepared using this approach.
- Blanco, Maria-Jesus,Sardina, F. Javier
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p. 4748 - 4755
(2007/10/03)
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