title: Fluorinated and Conformationally Fixed Derivatives of L-HomoDMDP: Synthesis and Glycosidase Inhibition.
abstract: Fluorinated and conformationally fixed derivatives of L-homoDMDP, i.e., 2,5-dideoxy-2,5-imino-DL-glycero-L-manno-heptitol, have been synthesized from d-xylose-derived cyclic nitrone 10 with oxazolidinone 19 or 28 and oxazinanone 22 or 32 as key intermediates. An evaluation of glycosidase inhibition showed replacement of the C-6 hydroxyl groups with fluoride in L-homoDMDP and its C-6 epimer did not have a significant influence on α-glucosidase inhibition by these iminosugars, while replacement of an amino group with a cyclic carbamate group in most conformationally fixed derivatives led to a sharp decrease in the level of glycosidase inhibition, revealing the importance of the free amino group in interaction of enzymes with these molecules.
authors.affiliation: †Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Yi-Xian
authors.initials: YX
authors.lastname: Li
authors.affiliation: ‡Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: ‡Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Adachi
authors.affiliation: ‡Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.affiliation: †Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Jia
authors.affiliation: §Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.|⊥National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, China.
authors.forename: George W J
authors.initials: GW
authors.lastname: Fleet
authors.affiliation: ∥State Key Laboratory of Microbial Technology and National Glycoengineering Research Center, Shandong University, Jinan 250100, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: †Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.|⊥National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, China.
authors.forename: Chu-Yi
authors.initials: CY
authors.lastname: Yu
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D054879:Halogenation; D050111:Imino Sugars / Q000138:chemical synthesis / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000737:chemistry*
chemical_list: C000603738:2,5-dideoxy-2,5-imino-DL-glycero-L-manno-heptitol; D004791:Enzyme Inhibitors; D050111:Imino Sugars; D023303:Oxazolidinones; D000520:alpha-Glucosidases