The Experts below are selected from a list of 2484 Experts worldwide ranked by ideXlab platform
Herman S. Overkleeft - One of the best experts on this subject based on the ideXlab platform.
-
synthesis of eight 1 Deoxynojirimycin isomers from a single chiral cyanohydrin
European Journal of Organic Chemistry, 2012Co-Authors: Adrianus M C H Van Den Nieuwendijk, Johannes Brussee, Richard J B H N Van Den Berg, Mark Ruben, Martin D. Witte, Gijsbert A Van Der Marel, Rene G A Boot, Johannes M F G Aerts, Herman S. OverkleeftAbstract:Eight configurational 1-Deoxynojirimycin isomers have been synthesized starting from a chiral cyanohydrin as the common precursor. The cyanohydrin chiral pool building block is easily accessible in large quantities by using almond hydroxynitrile lyase as the chiral catalyst in condensing hydrogen cyanide and crotonaldehyde. Our work complements the large body of literature on the synthesis of 1-Deoxynojirimycin derivatives with the distinguishing feature that eight stereoisomers of this important class of glycosidase inhibitors can be derived from a common precursor in an efficient manner.
-
synthesis of l altro 1 Deoxynojirimycin d allo 1 Deoxynojirimycin and d galacto 1 Deoxynojirimycin from a single chiral cyanohydrin
Organic Letters, 2010Co-Authors: Adrianus M C H Van Den Nieuwendijk, Johannes Brussee, Richard J B H N Van Den Berg, Mark Ruben, Gijsbert A Van Der Marel, Rene G A Boot, Sander E Engelsma, Martijn D P Risseeuw, Johannes M F G Aerts, Herman S. OverkleeftAbstract:The chemoenzymatic synthesis of three 1-Deoxynojirimycin-type iminosugars is reported. Key steps in the synthetic scheme include a Dibal reduction−transimination−sodium borohydride reduction cascade of reactions on an enantiomerically pure cyanohydrin, itself prepared employing almond hydroxynitrile lyase (paHNL) as the common precursor. Ensuing ring-closing metathesis and Upjohn dihydroxylation afford the target compounds.
-
Large-Scale Synthesis of the Glucosylceramide Synthase Inhibitor N-[5-(Adamantan-1-yl-methoxy)-pentyl]-1-Deoxynojirimycin
Organic Process Research & Development, 2008Co-Authors: Tom Wennekes, Gijsbert A Van Der Marel, Michel Leeman, Elly Smits, Jim Van Wiltenburg, Michael Wolberg, Matthias Weber, Bernhard Lang, Johannes M F G Aerts, Herman S. OverkleeftAbstract:A synthetic route for the preparation of glucosylceramide synthase inhibitor N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-Deoxynojirimycin methanesulfonic acid salt (AMP-DNM) has been developed. Herein we report the development and optimization of this synthetic route from its initial version in an academic research laboratory at milligram-scale to the final optimized route that was implemented in a cGMP miniplant on kilogram-scale. The definitive route starts with the separate synthesis of building blocks 2,3,4,6-tetra-O-benzyl-1-Deoxynojirimycin and 5-(adamantan-1-yl-methoxy)-pentanal. The aldehyde was synthesized from 1,5-pentanediol in five steps and 45% overall yield. Protected 1-Deoxynojirimycin was prepared by a successive hemiacetal reduction/Swern oxidation/double reductive amination sequence of 2,3,4,5-tetra-O-benzyl-d-glucopyranose in 52% overall yield. Reductive amination of the two building blocks produced the benzyl-protected penultimate that was isolated as its crystalline (+)DTTA salt in 68% yi...
-
Development of adamantan-1-yl-methoxy-functionalized 1-Deoxynojirimycin derivatives as selective inhibitors of glucosylceramide metabolism in man
The Journal of organic chemistry, 2007Co-Authors: Tom Wennekes, Johannes M F G Aerts, Richard J. B. H. N. Van Den Berg, Wilma Donker, Gijsbert A. Van Der Marel, Anneke Strijland, Herman S. OverkleeftAbstract:In this article, we present a straightforward synthesis of adamantan-1-yl-methoxy-functionalized 1-Deoxynojirimycin derivatives. The used synthetic routes are flexible and can be used to create a wide variety of lipophilic mono- and difunctionalized 1-Deoxynojirimycin derivatives. The compounds reported here are lipophilic iminosugar based on lead compound 4, a potent inhibitor of the three enzymes involved in the metabolism of the glycosphingolipid glucosylceramide. Iminosugar-based inhibitors of glucosylceramide synthase, one of these three enzymes, have attracted increasing interest over the past decade due to the crucial role of this enzyme in glycosphingolipid biosynthesis. Combined with the fact that an increasing number of pathological processes are being linked to excessive glycosphingolipid levels, glucosylceramide synthase becomes a very attractive therapeutic and research target. Our results presented here demonstrate that relocating the lipophilic moiety from the nitrogen atom to other positio...
Johannes M F G Aerts - One of the best experts on this subject based on the ideXlab platform.
-
synthesis of eight 1 Deoxynojirimycin isomers from a single chiral cyanohydrin
European Journal of Organic Chemistry, 2012Co-Authors: Adrianus M C H Van Den Nieuwendijk, Johannes Brussee, Richard J B H N Van Den Berg, Mark Ruben, Martin D. Witte, Gijsbert A Van Der Marel, Rene G A Boot, Johannes M F G Aerts, Herman S. OverkleeftAbstract:Eight configurational 1-Deoxynojirimycin isomers have been synthesized starting from a chiral cyanohydrin as the common precursor. The cyanohydrin chiral pool building block is easily accessible in large quantities by using almond hydroxynitrile lyase as the chiral catalyst in condensing hydrogen cyanide and crotonaldehyde. Our work complements the large body of literature on the synthesis of 1-Deoxynojirimycin derivatives with the distinguishing feature that eight stereoisomers of this important class of glycosidase inhibitors can be derived from a common precursor in an efficient manner.
-
synthesis of l altro 1 Deoxynojirimycin d allo 1 Deoxynojirimycin and d galacto 1 Deoxynojirimycin from a single chiral cyanohydrin
Organic Letters, 2010Co-Authors: Adrianus M C H Van Den Nieuwendijk, Johannes Brussee, Richard J B H N Van Den Berg, Mark Ruben, Gijsbert A Van Der Marel, Rene G A Boot, Sander E Engelsma, Martijn D P Risseeuw, Johannes M F G Aerts, Herman S. OverkleeftAbstract:The chemoenzymatic synthesis of three 1-Deoxynojirimycin-type iminosugars is reported. Key steps in the synthetic scheme include a Dibal reduction−transimination−sodium borohydride reduction cascade of reactions on an enantiomerically pure cyanohydrin, itself prepared employing almond hydroxynitrile lyase (paHNL) as the common precursor. Ensuing ring-closing metathesis and Upjohn dihydroxylation afford the target compounds.
-
Large-Scale Synthesis of the Glucosylceramide Synthase Inhibitor N-[5-(Adamantan-1-yl-methoxy)-pentyl]-1-Deoxynojirimycin
Organic Process Research & Development, 2008Co-Authors: Tom Wennekes, Gijsbert A Van Der Marel, Michel Leeman, Elly Smits, Jim Van Wiltenburg, Michael Wolberg, Matthias Weber, Bernhard Lang, Johannes M F G Aerts, Herman S. OverkleeftAbstract:A synthetic route for the preparation of glucosylceramide synthase inhibitor N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-Deoxynojirimycin methanesulfonic acid salt (AMP-DNM) has been developed. Herein we report the development and optimization of this synthetic route from its initial version in an academic research laboratory at milligram-scale to the final optimized route that was implemented in a cGMP miniplant on kilogram-scale. The definitive route starts with the separate synthesis of building blocks 2,3,4,6-tetra-O-benzyl-1-Deoxynojirimycin and 5-(adamantan-1-yl-methoxy)-pentanal. The aldehyde was synthesized from 1,5-pentanediol in five steps and 45% overall yield. Protected 1-Deoxynojirimycin was prepared by a successive hemiacetal reduction/Swern oxidation/double reductive amination sequence of 2,3,4,5-tetra-O-benzyl-d-glucopyranose in 52% overall yield. Reductive amination of the two building blocks produced the benzyl-protected penultimate that was isolated as its crystalline (+)DTTA salt in 68% yi...
-
Development of adamantan-1-yl-methoxy-functionalized 1-Deoxynojirimycin derivatives as selective inhibitors of glucosylceramide metabolism in man
The Journal of organic chemistry, 2007Co-Authors: Tom Wennekes, Johannes M F G Aerts, Richard J. B. H. N. Van Den Berg, Wilma Donker, Gijsbert A. Van Der Marel, Anneke Strijland, Herman S. OverkleeftAbstract:In this article, we present a straightforward synthesis of adamantan-1-yl-methoxy-functionalized 1-Deoxynojirimycin derivatives. The used synthetic routes are flexible and can be used to create a wide variety of lipophilic mono- and difunctionalized 1-Deoxynojirimycin derivatives. The compounds reported here are lipophilic iminosugar based on lead compound 4, a potent inhibitor of the three enzymes involved in the metabolism of the glycosphingolipid glucosylceramide. Iminosugar-based inhibitors of glucosylceramide synthase, one of these three enzymes, have attracted increasing interest over the past decade due to the crucial role of this enzyme in glycosphingolipid biosynthesis. Combined with the fact that an increasing number of pathological processes are being linked to excessive glycosphingolipid levels, glucosylceramide synthase becomes a very attractive therapeutic and research target. Our results presented here demonstrate that relocating the lipophilic moiety from the nitrogen atom to other positio...
Gijsbert A Van Der Marel - One of the best experts on this subject based on the ideXlab platform.
-
synthesis of eight 1 Deoxynojirimycin isomers from a single chiral cyanohydrin
European Journal of Organic Chemistry, 2012Co-Authors: Adrianus M C H Van Den Nieuwendijk, Johannes Brussee, Richard J B H N Van Den Berg, Mark Ruben, Martin D. Witte, Gijsbert A Van Der Marel, Rene G A Boot, Johannes M F G Aerts, Herman S. OverkleeftAbstract:Eight configurational 1-Deoxynojirimycin isomers have been synthesized starting from a chiral cyanohydrin as the common precursor. The cyanohydrin chiral pool building block is easily accessible in large quantities by using almond hydroxynitrile lyase as the chiral catalyst in condensing hydrogen cyanide and crotonaldehyde. Our work complements the large body of literature on the synthesis of 1-Deoxynojirimycin derivatives with the distinguishing feature that eight stereoisomers of this important class of glycosidase inhibitors can be derived from a common precursor in an efficient manner.
-
synthesis of l altro 1 Deoxynojirimycin d allo 1 Deoxynojirimycin and d galacto 1 Deoxynojirimycin from a single chiral cyanohydrin
Organic Letters, 2010Co-Authors: Adrianus M C H Van Den Nieuwendijk, Johannes Brussee, Richard J B H N Van Den Berg, Mark Ruben, Gijsbert A Van Der Marel, Rene G A Boot, Sander E Engelsma, Martijn D P Risseeuw, Johannes M F G Aerts, Herman S. OverkleeftAbstract:The chemoenzymatic synthesis of three 1-Deoxynojirimycin-type iminosugars is reported. Key steps in the synthetic scheme include a Dibal reduction−transimination−sodium borohydride reduction cascade of reactions on an enantiomerically pure cyanohydrin, itself prepared employing almond hydroxynitrile lyase (paHNL) as the common precursor. Ensuing ring-closing metathesis and Upjohn dihydroxylation afford the target compounds.
-
Large-Scale Synthesis of the Glucosylceramide Synthase Inhibitor N-[5-(Adamantan-1-yl-methoxy)-pentyl]-1-Deoxynojirimycin
Organic Process Research & Development, 2008Co-Authors: Tom Wennekes, Gijsbert A Van Der Marel, Michel Leeman, Elly Smits, Jim Van Wiltenburg, Michael Wolberg, Matthias Weber, Bernhard Lang, Johannes M F G Aerts, Herman S. OverkleeftAbstract:A synthetic route for the preparation of glucosylceramide synthase inhibitor N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-Deoxynojirimycin methanesulfonic acid salt (AMP-DNM) has been developed. Herein we report the development and optimization of this synthetic route from its initial version in an academic research laboratory at milligram-scale to the final optimized route that was implemented in a cGMP miniplant on kilogram-scale. The definitive route starts with the separate synthesis of building blocks 2,3,4,6-tetra-O-benzyl-1-Deoxynojirimycin and 5-(adamantan-1-yl-methoxy)-pentanal. The aldehyde was synthesized from 1,5-pentanediol in five steps and 45% overall yield. Protected 1-Deoxynojirimycin was prepared by a successive hemiacetal reduction/Swern oxidation/double reductive amination sequence of 2,3,4,5-tetra-O-benzyl-d-glucopyranose in 52% overall yield. Reductive amination of the two building blocks produced the benzyl-protected penultimate that was isolated as its crystalline (+)DTTA salt in 68% yi...
Adrianus M C H Van Den Nieuwendijk - One of the best experts on this subject based on the ideXlab platform.
-
synthesis of eight 1 Deoxynojirimycin isomers from a single chiral cyanohydrin
European Journal of Organic Chemistry, 2012Co-Authors: Adrianus M C H Van Den Nieuwendijk, Johannes Brussee, Richard J B H N Van Den Berg, Mark Ruben, Martin D. Witte, Gijsbert A Van Der Marel, Rene G A Boot, Johannes M F G Aerts, Herman S. OverkleeftAbstract:Eight configurational 1-Deoxynojirimycin isomers have been synthesized starting from a chiral cyanohydrin as the common precursor. The cyanohydrin chiral pool building block is easily accessible in large quantities by using almond hydroxynitrile lyase as the chiral catalyst in condensing hydrogen cyanide and crotonaldehyde. Our work complements the large body of literature on the synthesis of 1-Deoxynojirimycin derivatives with the distinguishing feature that eight stereoisomers of this important class of glycosidase inhibitors can be derived from a common precursor in an efficient manner.
-
synthesis of l altro 1 Deoxynojirimycin d allo 1 Deoxynojirimycin and d galacto 1 Deoxynojirimycin from a single chiral cyanohydrin
Organic Letters, 2010Co-Authors: Adrianus M C H Van Den Nieuwendijk, Johannes Brussee, Richard J B H N Van Den Berg, Mark Ruben, Gijsbert A Van Der Marel, Rene G A Boot, Sander E Engelsma, Martijn D P Risseeuw, Johannes M F G Aerts, Herman S. OverkleeftAbstract:The chemoenzymatic synthesis of three 1-Deoxynojirimycin-type iminosugars is reported. Key steps in the synthetic scheme include a Dibal reduction−transimination−sodium borohydride reduction cascade of reactions on an enantiomerically pure cyanohydrin, itself prepared employing almond hydroxynitrile lyase (paHNL) as the common precursor. Ensuing ring-closing metathesis and Upjohn dihydroxylation afford the target compounds.
Guo-ping Peng - One of the best experts on this subject based on the ideXlab platform.
-
A UPLC-MS/MS method for simultaneous determination of 1-Deoxynojirimycin and N-methyl-1-Deoxynojirimycin in rat plasma and its application in pharmacokinetic and absolute bioavailability studies.
Journal of Chromatography B, 2017Co-Authors: Tingting Liang, Fang Wang, Jia-mei Gu, Yang Lu, Weike Chen, Cunyu Li, Yun-feng Zheng, Guo-ping PengAbstract:Abstract A specific, sensitive, rapid, precise, and reliable UPLC–MS/MS-based method was designed for the first time for the simultaneous determination of 1-Deoxynojirimycin (DNJ) and N-methyl-1-Deoxynojirimycin (N-CH3-DNJ) in rat plasma. Miglitol was served as the internal standard (IS). An MN-NUCLEODUR HILIC column was assessed to separate the two compounds by isocratic elution using acetonitrile: water with 0.05% formic acid and 6.5 mM ammonium acetate (72:28, v/v) at a flow rate of 0.4 mL/min. A triple quadrupole mass spectrometer was operated in the positive ionization mode using multiple reaction monitoring (MRM), and it was employed to determine transitions of m/z 164.1 → 110.1, 178.1 → 100.1, and 208.1 → 146.1 for DNJ, N-CH3-DNJ, and IS, respectively. The method of the two constituents was validated and the results were acceptable. The absolute bioavailability of DNJ and N-CH3-DNJ in rats was 50 ± 9% and 62 ± 24%, respectively. The method was then successfully used for the first time to study the pharmacokinetic behavior and absolute bioavailability of DNJ and N-CH3-DNJ in rats after intravenous (10 mg/kg) and oral administration (80 mg/kg). The results of this study might provide more information on preclinical pharmacokinetics and a solid basis for assessing the clinical efficacy of DNJ and N-CH3-DNJ.
-
A UPLC-MS/MS method for simultaneous determination of 1-Deoxynojirimycin and N-methyl-1-Deoxynojirimycin in rat plasma and its application in pharmacokinetic and absolute bioavailability studies.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2017Co-Authors: Tingting Liang, Fang Wang, Weike Chen, Yun-feng Zheng, Shun Liu, Guo-ping PengAbstract:A specific, sensitive, rapid, precise, and reliable UPLC-MS/MS-based method was designed for the first time for the simultaneous determination of 1-Deoxynojirimycin (DNJ) and N-methyl-1-Deoxynojirimycin (N-CH3-DNJ) in rat plasma. Miglitol was served as the internal standard (IS). An MN-NUCLEODUR HILIC column was assessed to separate the two compounds by isocratic elution using acetonitrile: water with 0.05% formic acid and 6.5mM ammonium acetate (72:28, v/v) at a flow rate of 0.4mL/min. A triple quadrupole mass spectrometer was operated in the positive ionization mode using multiple reaction monitoring (MRM), and it was employed to determine transitions of m/z 164.1→110.1, 178.1→100.1, and 208.1→146.1 for DNJ, N-CH3-DNJ, and IS, respectively. The method of the two constituents was validated and the results were acceptable. The absolute bioavailability of DNJ and N-CH3-DNJ in rats was 50±9% and 62±24%, respectively. The method was then successfully used for the first time to study the pharmacokinetic behavior and absolute bioavailability of DNJ and N-CH3-DNJ in rats after intravenous (10mg/kg) and oral administration (80mg/kg). The results of this study might provide more information on preclinical pharmacokinetics and a solid basis for assessing the clinical efficacy of DNJ and N-CH3-DNJ.
