The l-enantiomers of d-sugar-mimicking iminosugars are noncompetitive inhibitors of d-glycohydrolase?

Asano, Naoki; Ikeda, Kyoko; Yu, Liang; Kato, Atsushi; Takebayashi, Kenji; Adachi, Isao; Kato, Ikuo; Ouchi, Hidekazu; Takahata, Hiroki; Fleet, George W. J.

doi:10.1016/j.tetasy.2004.11.067

Cited by 91 publications

(65 citation statements)

References 27 publications

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“…Nuclear magnetic resonance (NMR) data ( 1 H or 13 C) were obtained on a AC-Brucker 300 machine, and chemical shifts are reported in parts per million relative to tetramethylsilane in deuterated solvents. Assignments of 1 H and 13 C were assisted by 2D 1 H COSY and 2D 1 H- 13 C CORR experiments.…”

Section: Methodsmentioning

confidence: 99%

“…In the 13 C NMR of the compounds 7a-p, characteristic (C=O) appeared at around 168.76 to 170.20 and characteristic (C=O) products (7a -p ) were recorded at around 169.38-171.31 ppm. The 13 C NMR spectrum of all the compounds showed the characteristic of signal for the (C (Me) 2 ) of isopropylidene at around 112.93 to 112.32 ppm.…”

Section: Amine (6) With the 23-o-isopropylidene-d-erythruronolactonementioning

confidence: 98%

“…The 1,4-dideoxy-1,4-imino-L-arabinitol (LAB, 3) (Figure 2) was first found in the fruits of angylocalyx boutiqueanus (Fabaceae) [11], which is a powerful inhibitor of sucrase and α-glucosidases [13].…”

Section: Introductionmentioning

confidence: 99%

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One-Pot Synthesis of Pyrrolidine-2-ones from Erythruronolactone and Amine

Benhaoua

2012

Organic Chemistry International

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Section: Methodsmentioning

confidence: 99%

Section: Amine (6) With the 23-o-isopropylidene-d-erythruronolactonementioning

confidence: 98%

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One-Pot Synthesis of Pyrrolidine-2-ones from Erythruronolactone and Amine

Benhaoua

2012

Organic Chemistry International

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“…Furthermore, benzyl or dimethyl substituents at C-5, (e.g., entries [19][20][21][22] completely suppressed the activity of the corresponding pyrrolidine derivatives ( Figure 5, top). Altogether, these results suggest a relatively small hydrophobic pocket in the active site of a-lfucosidase, which could be occupied by small substituents on C-5 position, but not the larger ones.…”

Section: Wwwchemeurjorgmentioning

confidence: 99%

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

Calveras

Egido‐Gabás

Gómez

et al. 2009

Chemistry A European J

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The chemoenzymatic synthesis of a collection of pyrrolidine-type iminosugars generated by the aldol addition of dihydroxyacetone phosphate (DHAP) to C-alpha-substituted N-Cbz-2-aminoaldehydes derivatives, catalyzed by DHAP aldolases is reported. L-fuculose-1-phosphate aldolase (FucA) and L-rhamnulose-1-phosphate aldolase (RhuA) from E. coli were used as biocatalysts to generate configurational diversity on the iminosugars. Alkyl linear substitutions at C-alpha were well tolerated by FucA catalyst (i.e., 40-70 % conversions to aldol adduct), whereas no product was observed with C-alpha-alkyl branched substitutions, except for dimethyl and benzyl substitutions (20 %). RhuA was the most versatile biocatalyst: C-alpha-alkyl linear groups gave the highest conversions to aldol adducts (60-99 %), while the C-alpha-alkyl branched ones gave moderate to good conversions (50-80 %), with the exception of dimethyl and benzyl substituents (20 %). FucA was the most stereoselective biocatalyst (90-100 % anti (3R,4R) adduct). RhuA was highly stereoselective with (S)-N-Cbz-2-aminoaldehydes (90-100 % syn (i.e., 3R,4S) adduct), whereas those with R configuration gave mixtures of anti/syn adducts. For iPr and iBu substituents, RhuA furnished the anti adduct (i.e., FucA stereochemistry) with high stereoselectivity. Molecular models of aldol products with iPr and iBu substituents and as complexes with the RhuA active site suggest that the anti adducts could be kinetically preferred, while the syn adducts would be the equilibrium products. The polyhydroxylated pyrrolidines generated were tested as inhibitors against seven glycosidases. Among them, good inhibitors of alpha-L-fucosidase (IC50=1-20 microM), moderate of alpha-L-rhamnosidase (IC50=7-150 microM), and weak of alpha-D-mannosidase (IC50=80-400 microM) were identified. The apparent inhibition constant values (Ki) were calculated for the most relevant inhibitors and computational docking studies were performed to understand both their binding capacity and the mode of interaction with the glycosidases.

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“…Recently, the l-enantiomer of DMDP was synthesized from d-gulonolactone and found to be a more powerful and more specific -glucosidase inhibitor than the natural product DMDP [38]. More interestingly, the natural d-enantiomer is a competitive inhibitor of -d-glucohydrolases but its synthetic l-enantiomer is a noncompetitive inhibitor [39]. Similarly, the l-enantiomer of DAB was found to be a more potent inhibitor of mammalian digestive -glucosidases than the enantiomeric natural product DAB and also to be a noncompetitive inhibitor [39].…”

Section: -Glucosidase Inhibitors 221 Structures and In Vitro Inhibimentioning

confidence: 99%

The l-enantiomers of d-sugar-mimicking iminosugars are noncompetitive inhibitors of d-glycohydrolase?

Cited by 91 publications

References 27 publications

One-Pot Synthesis of Pyrrolidine-2-ones from Erythruronolactone and Amine

One-Pot Synthesis of Pyrrolidine-2-ones from Erythruronolactone and Amine

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

Naturally Occurring Iminosugars and Related Alkaloids: Structure, Activity and Applications

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