L-DMDP, l-homoDMDP and their C-3 fluorinated derivatives: Synthesis and glycosidase-inhibition

Yi Xian Li; Mu Hua Huang; Yukiko Yamashita; Atsushi Kato; Yue Mei Jia; Wu Bao Wang; George W.J. Fleet; Robert J. Nash; Chu Yi Yu

doi:10.1039/c0ob01063d

L-DMDP, l-homoDMDP and their C-3 fluorinated derivatives: Synthesis and glycosidase-inhibition

Yi Xian Li, Mu Hua Huang, Yukiko Yamashita, Atsushi Kato, Yue Mei Jia, Wu Bao Wang, George W.J. Fleet, Robert J. Nash, Chu Yi Yu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

l-DMDP and l-homoDMDP, the enantiomers of naturally occurring DMDP and homoDMDP have been synthesized from d-xylose derived cyclic nitrone 9. Their 3-deoxy-3-fluorinated analogues were also obtained from polyhydroxylated fluorinated cyclic nitrone 10, which was prepared from fluorinated sugar 12 in seven steps. Bioactivities of these iminosugars against various glycosidases were evaluated. While l-DMDP and l-homoDMDP are potent inhibitors of α-glucosidases, a sharp decrease of inhibition was found when the C-3 hydroxyl group of these compounds was replaced by fluoride, which showed the great importance of the C-3 hydroxyl in their interaction with enzymes.

Original language	English
Pages (from-to)	3405-3414
Number of pages	10
Journal	Organic and Biomolecular Chemistry
Volume	9
Issue number	9
DOIs	https://doi.org/10.1039/c0ob01063d
Publication status	Published - 7 May 2011
Externally published	Yes

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title = "L-DMDP, l-homoDMDP and their C-3 fluorinated derivatives: Synthesis and glycosidase-inhibition",

abstract = "l-DMDP and l-homoDMDP, the enantiomers of naturally occurring DMDP and homoDMDP have been synthesized from d-xylose derived cyclic nitrone 9. Their 3-deoxy-3-fluorinated analogues were also obtained from polyhydroxylated fluorinated cyclic nitrone 10, which was prepared from fluorinated sugar 12 in seven steps. Bioactivities of these iminosugars against various glycosidases were evaluated. While l-DMDP and l-homoDMDP are potent inhibitors of α-glucosidases, a sharp decrease of inhibition was found when the C-3 hydroxyl group of these compounds was replaced by fluoride, which showed the great importance of the C-3 hydroxyl in their interaction with enzymes.",

author = "Li, {Yi Xian} and Huang, {Mu Hua} and Yukiko Yamashita and Atsushi Kato and Jia, {Yue Mei} and Wang, {Wu Bao} and Fleet, {George W.J.} and Nash, {Robert J.} and Yu, {Chu Yi}",

year = "2011",

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doi = "10.1039/c0ob01063d",

language = "English",

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journal = "Organic and Biomolecular Chemistry",

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T1 - L-DMDP, l-homoDMDP and their C-3 fluorinated derivatives

T2 - Synthesis and glycosidase-inhibition

AU - Li, Yi Xian

AU - Huang, Mu Hua

AU - Yamashita, Yukiko

AU - Kato, Atsushi

AU - Jia, Yue Mei

AU - Wang, Wu Bao

AU - Fleet, George W.J.

AU - Nash, Robert J.

AU - Yu, Chu Yi

PY - 2011/5/7

Y1 - 2011/5/7

N2 - l-DMDP and l-homoDMDP, the enantiomers of naturally occurring DMDP and homoDMDP have been synthesized from d-xylose derived cyclic nitrone 9. Their 3-deoxy-3-fluorinated analogues were also obtained from polyhydroxylated fluorinated cyclic nitrone 10, which was prepared from fluorinated sugar 12 in seven steps. Bioactivities of these iminosugars against various glycosidases were evaluated. While l-DMDP and l-homoDMDP are potent inhibitors of α-glucosidases, a sharp decrease of inhibition was found when the C-3 hydroxyl group of these compounds was replaced by fluoride, which showed the great importance of the C-3 hydroxyl in their interaction with enzymes.

AB - l-DMDP and l-homoDMDP, the enantiomers of naturally occurring DMDP and homoDMDP have been synthesized from d-xylose derived cyclic nitrone 9. Their 3-deoxy-3-fluorinated analogues were also obtained from polyhydroxylated fluorinated cyclic nitrone 10, which was prepared from fluorinated sugar 12 in seven steps. Bioactivities of these iminosugars against various glycosidases were evaluated. While l-DMDP and l-homoDMDP are potent inhibitors of α-glucosidases, a sharp decrease of inhibition was found when the C-3 hydroxyl group of these compounds was replaced by fluoride, which showed the great importance of the C-3 hydroxyl in their interaction with enzymes.

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SN - 1477-0520

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JO - Organic and Biomolecular Chemistry

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ER -

L-DMDP, l-homoDMDP and their C-3 fluorinated derivatives: Synthesis and glycosidase-inhibition

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