A facile transformation of sugar lactones to azasugars

Overkleeft, Herman S.; Wiltenburg, Jim van; Pandit, U. K.

doi:10.1016/s0040-4020(01)86715-6

Cited by 121 publications

(70 citation statements)

References 18 publications

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“…Deoxynojirimycin (DNM) 2 was prepared from tetra-O-benzylglucopyranose according to the literature procedure (5). NPropyl-, N-butyl-, N-pentyl-, and N-heptyl-DNM were prepared by literature procedure (6 -8) by treatment of DNM HCl with the appropriate aldehyde under the agency of sodium cyanoborohydride and acetic acid.…”

Section: Synthesis Of Inhibitorsmentioning

confidence: 99%

Generation of Specific Deoxynojirimycin-type Inhibitors of the Non-lysosomal Glucosylceramidase

Overkleeft¹,

Renkema²,

Neele³

et al. 1998

Journal of Biological Chemistry

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171

201

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The existence of a non-lysosomal glucosylceramidase in human cells has been documented (van Weely, S., Brandsma, M., Strijland, A., Tager, J. M., and Aerts, J. M. F. G. (1993) Biochim. Biophys. Acta 1181, 55-62). Hypothetically, the activity of this enzyme, which is localized near the cell surface, may influence ceramidemediated signaling processes. To obtain insight in the physiological importance of the non-lysosomal glucosylceramidase, the availability of specific inhibitors would be helpful. Here we report on the generation of hydrophobic deoxynojirimycin (DNM) derivatives that potently inhibit the enzyme. The inhibitors were designed on the basis of the known features of the non-lysosomal glucosylceramidase and consist of a DNM moiety, an N-alkyl spacer, and a large hydrophobic group that promotes insertion in membranes. In particular, N-(5-adamantane-1-yl-methoxy)pentyl)-DNM is a very powerful inhibitor of the non-lysosomal glucosylceramidase at nanomolar concentrations. At such concentrations, the lysosomal glucocerebrosidase and ␣-glucosidase, the glucosylceramide synthase, and the N-linked glycantrimming ␣-glucosidases of the endoplasmic reticulum are not affected.

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Section: Synthesis Of Inhibitorsmentioning

confidence: 99%

Generation of Specific Deoxynojirimycin-type Inhibitors of the Non-lysosomal Glucosylceramidase

Overkleeft¹,

Renkema²,

Neele³

et al. 1998

Journal of Biological Chemistry

Self Cite

171

201

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“…Part) were assigned on the basis of a HSQC-GRASP spectrum; those of the lactone 17, the amides 18 and 19, the lactams 22 -26, and the imide 27 were assigned by analogy. Like the tetrabenzyl analogue [29], the galactonolactams 22 -26 adopt a 4 H 3 conformation in CDCl 3 as evidenced by large J(2,3), and small J(3,4) and J (4,5) values (see Table 2 in Exper. Part).…”

mentioning

confidence: 99%

Synthesis of Glycaro‐1,5‐lactams and Tetrahydrotetrazolopyridine‐5‐carboxylates: Inhibitors of β‐D‐Glucuronidase and α‐L‐Iduronidase

Pabba

Rempel

Withers

et al. 2006

Helvetica Chimica Acta

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The known glucaro-1,5-lactam 8, its diastereoisomers 9 -11, and the tetrahydrotetrazolopyridine-5-carboxylates 12 -14 were synthesised as potential inhibitors of b-D-glucuronidases and a-L-iduronidases. The known 2,3-di-O-benzyl-4,6-O-benzylidene-D-galactose (16) was transformed into the D-galactaroand L-altraro-1,5-lactams 9 and 11 via the galactono-1,5-lactam 21 in twelve steps and in an overall yield of 13 and 2%, respectively. A divergent strategy, starting from the known tartaric anhydride 41, led to the D-glucaro-1,5-lactam 8, D-galactaro-1,5-lactam 9, L-idaro-1,5-lactam 10, and L-altraro-1,5-lactam 11 in ten steps and in an overall yield of 4 -20%. The anhydride 41 was transformed into the L-thre-A C H T U N G T R E N N U N G uronate 46. Olefination of 46 to the (E)-or (Z)-alkene 47 or 48 followed by reagent-or substrate-controlled dihydroxylation, lactonisation, azidation, reduction, and deprotection led to the lactams 8 -11. The tetrazoles 12 -14 were prepared in an overall yield of 61 -81% from the lactams 54, 28, and 67, respectively, by treatment with Tf 2 A C H T U N G T R E N N U N G O and NaN 3 , followed by saponification, esterification, and hydrogen-A C H T U N G T R E N N U N G olysis. The lactams 8 -11 and 40 and the tetrazoles 12 -14 are medium-to-strong inhibitors of b-D-glucuronidase from bovine liver. Only the L-ido-configured lactam 10 (K i = 94 mM) and the tetrazole 14Introduction. -b-D-Glucuronidases (EC 3.2.1.31, family 2) 1 ) and a-L-iduronidases (EC 3.2.1.76, family 39) remove glycuronic acid residues from the non-reducing end of glycosaminoglycans such as chondroitin sulfate and hyaluronic acid.

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“…conditions (Overkleeft et al, 1994) provided the desired polyhydroxy 2-pyrrolidinone 7 in 45% yield.…”

Section: Synthesis Of Polyhydroxy 2-pyrrolidinone 7 From D-galactosementioning

confidence: 97%

Design and synthesis of a novel glycosphingolipid derived from polyhydroxy 2-pyrrolidinone and phytoceramide appended by a 1,2,3-triazole linker

Gorantla

Faseela

Lankalapalli

2016

Chemistry and Physics of Lipids

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A facile transformation of sugar lactones to azasugars

Cited by 121 publications

References 18 publications

Generation of Specific Deoxynojirimycin-type Inhibitors of the Non-lysosomal Glucosylceramidase

Generation of Specific Deoxynojirimycin-type Inhibitors of the Non-lysosomal Glucosylceramidase

Synthesis of Glycaro‐1,5‐lactams and Tetrahydrotetrazolopyridine‐5‐carboxylates: Inhibitors of β‐D‐Glucuronidase and α‐L‐Iduronidase

Design and synthesis of a novel glycosphingolipid derived from polyhydroxy 2-pyrrolidinone and phytoceramide appended by a 1,2,3-triazole linker

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A facile transformation of sugar lactones to azasugars

Cited by 121 publications

References 18 publications

Generation of Specific Deoxynojirimycin-type Inhibitors of the Non-lysosomal Glucosylceramidase

Generation of Specific Deoxynojirimycin-type Inhibitors of the Non-lysosomal Glucosylceramidase

Synthesis of Glycaro‐1,5‐lactams and Tetrahydrotetrazolopyridine‐5‐carboxylates: Inhibitors of β‐D‐Glucuronidase and α‐L‐Iduronidase

Design and synthesis of a novel glycosphingolipid derived from polyhydroxy 2-pyrrolidinone and phytoceramide appended by a 1,​2,​3-​triazole linker

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Design and synthesis of a novel glycosphingolipid derived from polyhydroxy 2-pyrrolidinone and phytoceramide appended by a 1,2,3-triazole linker