Iminoheptitols as glycosidase inhibitors: synthesis of and specific α-L-fucosidase inhibition by β-L-homofuconojirimycin and 1-β-C-substituted deoxymannojirimycins

Fleet, George W. J.; Namgoong, Sung Keon; Barker, Christopher; Baines, S.; Jacob, Gary S.; Winchester, Bryan

doi:10.1016/s0040-4039(00)99383-3

Cited by 75 publications

(37 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As Rha-DMJ exhibited no significant inhibition against any other glycosidases tested, it is a specific inhibitor of a-l-fucosidases. b-HFJ (13) has been chemically synthesized from l-gulonolactone and found to be a powerful competitive inhibitor of human liver a-l-fucosidase, with a K i value of 10 nm [11,19]. In the present study, a natural sample gave K i values of 5.3 nm for bovine epididymis a-l-fucosidase and 10 nm for human placenta a-l-fucosidase.…”

Section: Inhibition Of A-l-fucosidase By Sugar-mimic Alkaloidsmentioning

confidence: 56%

“…Compound 12 was identified as the first naturally occurring glycoside of DMJ, 6-O-a-l-rhamnopyranosyl-DMJ, and compounds 14 and 15 to be the new isomers of 1-deoxynojirimycin (DNJ), 1-deoxyaltronojirimycin and 1-deoxygulonojirimycin, respectively. The structure of compound 13 deduced from NMR data was identical with that of b-l-homofuconojirimycin, which has been chemically synthesized only by Fleet et al [11], and its specific rotation value was also in accord with that of a synthetic sample. 2,5-Imino-2,5,6-trideoxy-d-gulo-heptitol (d-gulo-6-deoxy-homoDMDP), a-homomannojirimycin (a-HMJ) and b-homomannojirimycin (b-HMJ) were isolated from the bulbs of Hyacinthus orientalis according to the literature [12].…”

Section: Inhibitorsmentioning

confidence: 57%

See 1 more Smart Citation

Novel α‐L‐fucosidase inhibitors from the bark of Angylocalyx pynaertii (Leguminosae)

Asano

Yasuda

Kizu

et al. 2001

European Journal of Biochemistry

View full text Add to dashboard Cite

The extract of bark of Angylocalyx pynaertii (Leguminosae) was found to potently inhibit mammalian a-l-fucosidases. A thorough examination of the extract resulted in the discovery of 15 polyhydroxylated alkaloids, including the known alkaloids from seeds of this plant, 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), 1-deoxymannojirimycin (DMJ) and 2,5-imino-1,2,5-trideoxy-d-mannitol (6-deoxy-DMDP). Among them, eight sugar-mimic alkaloids showed the potent inhibitory activity towards bovine epididymis a-l-fucosidase and their K i values are as follows: 6-deoxy-DMDP (83 mm), 2,5-imino-1,2,5-trideoxy-l-glucitol (0.49 mm), 2,5-dideoxy-2,5-imino-d-fucitol (17 mm), 2,5-imino-1,2,5-trideoxy-d-altritol (3.7 mm), DMJ (4.7 mm), N-methyl-DMJ (30 mm), 6-O-a-l-rhamnopyranosyl-DMJ (Rha-DMJ, 0.06 mm), and b-l-homofuconojirimycin (b-HFJ, 0.0053 mm). We definitively deduced the structural requirements of inhibitors of a-l-fucosidase for the piperidine alkaloids (DMJ derivatives). The minimum structural feature of a-l-fucosidase inhibitors is the correct configuration of the three hydroxyl groups on the piperidine ring corresponding to C2, C3 and C4 of l-fucose. Furthermore, the addition of a methyl group in the correct configuration to the ring carbon atom corresponding to C5 of l-fucose generates extremely powerful inhibition of a-l-fucosidase. The replacement of the methyl group of b-HFJ by a hydroxymethyl group reduced its inhibitory potential about 80-fold. This suggests that there may be a hydrophobic region in or around the active site. The existence or configuration of a substituent group on the ring carbon atom corresponding to the anomeric position of l-fucose does not appear to be important for the inhibition. Interestingly, Rha-DMJ was a 70-fold more potent inhibitor of a-l-fucosidase than DMJ. This implies that the lysosomal a-l-fucosidase may have subsites recognizing oligosaccharyl structures in natural substrates.

show abstract

Section: Inhibition Of A-l-fucosidase By Sugar-mimic Alkaloidsmentioning

confidence: 56%

Section: Inhibitorsmentioning

confidence: 57%

Novel α‐L‐fucosidase inhibitors from the bark of Angylocalyx pynaertii (Leguminosae)

Asano

Yasuda

Kizu

et al. 2001

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…1-Deoxy-or homo-L L-fuco-nojirimycin derivatives L L-1a, L L-1c are nanomolar inhibitors of a-L L-fucosidase from various sources. [4][5][6][7][8] Amino-L L-lyxose sugar 2b 9,10 and its 1-deoxy-derivative 2a [9][10][11] are likewise potent inhibitors of the a-L L-fucosidase of bovine kidney; the a-homo derivative 2c has also a K i value in the nanomolar range. 12 We describe the asymmetric synthesis and the enzymatic evaluation of the L L-fuco-nojirimycin L L-1b, which is a new analogue of nojirimycin and which looks like a promising fucosidase inhibitor.…”

mentioning

confidence: 99%

Asymmetric synthesis of the l-fuco-nojirimycin, a nanomolar α-l-fucosidase inhibitor

Dubernet

Defoin

Tarnus

2006

Bioorganic & Medicinal Chemistry Letters

View full text Add to dashboard Cite

“…Such azasugars are believed to show increased enzyme inhibition and enhanced bioavailability 108 that by using a small nucleophilic hydride (from LiAlH 4 ) the correct sense was obtained in product 216. Adenophorine 13 was obtained on typical deprotection.…”

Section: The Synthesis Of Homomannojirimycin (Hmj) and Adenophorinementioning

confidence: 99%

Recent advances in the chemistry of azapyranose sugars

Afarinkia

Bahar

2005

Tetrahedron: Asymmetry

230

View full text Add to dashboard Cite

Iminoheptitols as glycosidase inhibitors: synthesis of and specific α-L-fucosidase inhibition by β-L-homofuconojirimycin and 1-β-C-substituted deoxymannojirimycins

Cited by 75 publications

References 10 publications

Novel α‐L‐fucosidase inhibitors from the bark of Angylocalyx pynaertii (Leguminosae)

Novel α‐L‐fucosidase inhibitors from the bark of Angylocalyx pynaertii (Leguminosae)

Asymmetric synthesis of the l-fuco-nojirimycin, a nanomolar α-l-fucosidase inhibitor

Recent advances in the chemistry of azapyranose sugars

Contact Info

Product

Resources

About