449729-69-5Relevant academic research and scientific papers
N-Alkyl-1,5-dideoxy-1,5-imino-L-fucitols as fucosidase inhibitors: Synthesis, molecular modelling and activity against cancer cell lines
Zhou, Jian,Negi, Arvind,Mirallai, Styliana I.,Warta, Rolf,Herold-Mende, Christel,Carty, Michael P.,Ye, Xin-Shan,Murphy, Paul V.
, p. 418 - 433 (2019)
1,5-Dideoxy-1,5-imino-L-fucitol (1-deoxyfuconojirimycin, DFJ) is an iminosugar that inhibits fucosidases. Herein, N-alkyl DFJs have been synthesised and tested against the α-fucosidases of T. maritima (bacterial origin) and B. taurus (bovine origin). The
In vitro and in vivo comparative and competitive activity-based protein profiling of GH29 α-L-fucosidases
Jiang, Jianbing,Kallemeijn, Wouter W.,Wright, Daniel W.,Van Den Nieuwendijk, Adrianus M. C. H.,Rohde, Veronica Coco,Folch, Elisa Colomina,Van Den Elst, Hans,Florea, Bogdan I.,Scheij, Saskia,Donker-Koopman, Wilma E.,Verhoek, Marri,Li, Nan,Schürmann, Martin,Mink, Daniel,Boot, Rolf G.,Codée, Jeroen D. C.,Van Der Marel, Gijsbert A.,Davies, Gideon J.,Aerts, Johannes M. F. G.,Overkleeft, Herman S.
, p. 2782 - 2789 (2015)
GH29 α-L-fucosidases catalyze the hydrolysis of α-L-fucosidic linkages. Deficiency in human lysosomal α-L-fucosidase (FUCA1) leads to the recessively inherited disorder, fucosidosis. Herein we describe the development of fucopyranose-configured cyclophellitol aziridines as activity-based probes (ABPs) for selective in vitro and in vivo labeling of GH29 α-L-fucosidases from bacteria, mice and man. Crystallographic analysis on bacterial α-L-fucosidase confirms that the ABPs act by covalent modification of the active site nucleophile. Competitive activity-based protein profiling identified l-fuconojirimycin as the single GH29 α-L-fucosidase inhibitor from eight configurational isomers.
Deoxygenative olefination reaction as the key step in the syntheses of deoxy and iminosugars
Hsu, Yung Chang,Hwu, Jih Ru
, p. 7686 - 7690 (2012)
Just a spoonful of sugar! A new synthetic strategy involving the use of a deoxygenative olefination reaction as the key step was developed for the preparation of deoxy and iminosugars in their optically active form (see scheme). This strategy has been proven successful by the use of a pentose, hexose, heptose, and disaccharide as the starting materials. Furthermore, it was applied in a formal total synthesis of iminosugar (-)-1-deoxy-l- fuconojirimycin, which can inhibit a-l-fucosidase.
A Straightforward Synthesis of (+/-) 5-Amino-5,6-Dideoxyallose, of its Bisulfite β-Anomer, and of its 1-Deoxy Derivative.
Defoin, Albert,Sarazin, Herve,Streith, Jacques
, p. 4327 - 4330 (1993)
Diels-Alder cycloaddition of (E,E)-hexadienal dimethylacetal 3 with the benzyloxycarbonylnitroso dienophile 4, followed by catalytic osmylation, hydrogenolysis, and treatment with SO2, led stereospecifically to the sole β-anomer of allopiperidinose bisulfite derivative 7.Saponification of 7 and thence catalytic hydrogenation gave in high yield the 1-deoxyallopiperidine derivative 9.
Total synthesis of pipecolic acid and 1-: C -alkyl 1,5-iminopentitol derivatives by way of stereoselective aldol reactions from (S)-isoserinal
Ba?, Sebastian,Kusy, Rafa?,Pasternak-Suder, Monika,Nicolas, Cyril,Mlynarski, Jacek,Martin, Olivier R.
, p. 1118 - 1125 (2018/02/21)
A short synthesis of iminosugars and pipecolic acid derivatives has been realized through aldol addition of a pyruvate, a range of ketones and (S)-isoserinal, followed by catalytic reductive intramolecular amination. The stereoselective aldol reaction was achieved successfully by using tertiary amines or di-zinc aldol catalysts, thus constituting two parallel routes to optically pure products with good yields and high diastereo-selectivities. These carbohydrate analogues may be the inhibitors of potent glycosidases and glycosyltransferases.
Accessing 2-substituted piperidine iminosugars by organometallic addition/intramolecular reductive amination: Aldehyde: vs. nitrone route
Mirabella,Fibbi,Matassini,Faggi,Goti,Cardona
, p. 9121 - 9126 (2017/11/14)
A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is disclosed. The procedure involved Grignard addition either to a carbohydrate-derived aldehyde or to a nitrone derived thereof, and took advantage of an efficient ring-closure reductive amination strategy in the final cyclization step. An opposite diastereofacial preference was demonstrated in the nucleophilic attack to the two electrophiles, which would finally produce the same piperidine diastereoisomer as the major product. However, use of a suitable Lewis acid in the Grignard addition to the nitrone allowed reversing the selectivity, giving access to 2-substituted piperidines with the opposite configuration at C-2.
Alternative synthesis and antibacterial evaluation of 1,5-dideoxy-1,5-imino-l-rhamnitol
Dharuman, Suresh,Wang, Yichen,Crich, David
, p. 29 - 32 (2016/01/09)
A convenient synthesis is described of 5-azido-5-deoxy-2,3-O-isopropylidene-l-rhamnofuranose from l-rhamnose in seven steps and 17% overall yield. A key feature of the synthesis is the selective oxidation of the secondary alcohol in 2,3-O-isopropylidene-l
Organocatalytic syn-aldol reactions of hydroxy ketones with (S)-isoserinal: Asymmetric synthesis of 6-deoxy-1,5-iminohexitols and related compounds
Nicolas, Cyril,Pluta, Roman,Pasternak-Suder, Monika,Martin, Olivier R.,Mlynarski, Jacek
, p. 1296 - 1305 (2013/04/10)
An improved and convenient preparation of protected (S)-isoserinal on a large scale is reported. This key intermediate was reacted through organocatalyzed aldol reaction or Wittig based chain extension and functionalization to give enantiopure 1,5,6-trideoxy-1,5-imino-hexitols such as 10a (L-manno) and 10b (D-gluco). These two compounds are of interest as glycosidase inhibitors. The elaborated organocatalytic process includes diastereoselective syn aldol reaction of (S)-isoserinal hydrate and hydroxyacetone or 1-hydroxy-2-octanone and is promoted by various amino acid-based catalysts. Diastereoselectivities of up to 8:1 were achieved, thus establishing a new, efficient synthetic route to these important carbohydrate mimics. A novel protocol for the preparation of 1,5,6-trideoxy-1,5-imino-L- mannitol and 1,5,6-trideoxy-1,5-imino-D-glucitol is reported. The key steps include organocatalyzed syn-selective direct aldol reaction of hydroxyacetone and CBz-protected isoserinal hydrate, followed by reductive amination/ cyclization. Copyright
Asymmetric syntheses of 6-deoxyfagomin, d-deoxyrhamnojirimycin, and d-rhamnono-1,5-lactam
Fu, Rui,Du, Yu,Li, Zhao-Ying,Xu, Wei-Xuan,Huang, Pei-Qiang
experimental part, p. 9765 - 9771 (2010/01/16)
N-Allyl protected 3-O-benzyloxglutarimide 11 was synthesized as a useful variant of the chiral building block 10. This modification allowed a high-yielding deprotection of the allyl group from the lactam intermediate 14. Starting from this building block,
New building block for polyhydroxylated piperidine: Total synthesis of 1,6-dideoxynojirimycin
Rengasamy, Rajesh,Curtis-Long, Marcus J.,Woo, Duck Seo,Seong, Hun Jeong,Jeong, Ill-Yun,Ki, Hun Park
, p. 2898 - 2901 (2008/09/19)
(Chemical Equation Presented) (3R,4S)-3-Hydroxy-4-N-allyl-N-Boc-amino-1- pentene 10, an important precursor for the synthesis of polyhydroxylated piperidines, has been achieved as a single diastereomer without racemization via vinyl Grignard addition to N-Boc-N-allyl aminoaldehyde 9, which was derived from an enantiopure natural amino acid. Having forged a tetrahydropyridine ring scaffold 13 from 10 in 85% yield via RCM using Grubbs II catalyst, we were able to effect its stereodivergent dihydroxylation, via a common epoxide intermediate to yield a range of interesting hydroxylated piperidines, including ent-1,6-dideoxynojirimycin (ent-1,6-dDNJ) 1 (28% overall yield) and 5-amino-1,5,6-trideoxyaltrose 2 (29% over all yield) in excellent dr. To the best of our knowledge, our synthesis of ent-1,6-dDNJ 1 is the most expeditious to date.
