4-C-Me-DAB and 4-C-Me-LAB - Enantiomeric alkyl-branched pyrrolidine iminosugars - Are specific and potent α-glucosidase inhibitors; Acetone as the sole protecting group

Filipa P.Da Cruz; Scott Newberry; Sarah F. Jenkinson; Mark R. Wormald; Terry D. Butters; Dominic S. Alonzi; Shinpei Nakagawa; Frederic Becq; Caroline Norez; Robert J. Nash; Atsushi Kato; George W.J. Fleet

doi:10.1016/j.tetlet.2010.10.173

4-C-Me-DAB and 4-C-Me-LAB - Enantiomeric alkyl-branched pyrrolidine iminosugars - Are specific and potent α-glucosidase inhibitors; Acetone as the sole protecting group

Filipa P.Da Cruz, Scott Newberry, Sarah F. Jenkinson, Mark R. Wormald, Terry D. Butters, Dominic S. Alonzi, Shinpei Nakagawa, Frederic Becq, Caroline Norez, Robert J. Nash, Atsushi Kato, George W.J. Fleet

薬剤部

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

42 被引用数 (Scopus)

抄録

The syntheses of 4-C-Me-DAB [1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pK_a of the salt around 8.4] is discussed and illustrates the need for care in the analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase K_i 0.89 μM, IC ₅₀ 0.41 μM) is a competitive - whereas 4-C-Me-LAB (for rat intestinal sucrase K_i 0.95 μM, IC₅₀ 0.66 μM) is a non-competitive - specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB and isoDAB - but not isoLAB - is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.

本文言語	英語
ページ（範囲）	219-223
ページ数	5
ジャーナル	Tetrahedron Letters
巻	52
号	2
DOI	https://doi.org/10.1016/j.tetlet.2010.10.173
出版ステータス	出版済み - 2011/01/12

ASJC Scopus 主題領域

生化学
創薬
有機化学

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10.1016/j.tetlet.2010.10.173

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引用スタイル

Cruz, F. P. D., Newberry, S., Jenkinson, S. F., Wormald, M. R., Butters, T. D., Alonzi, D. S., Nakagawa, S., Becq, F., Norez, C., Nash, R. J., Kato, A., & Fleet, G. W. J. (2011). 4-C-Me-DAB and 4-C-Me-LAB - Enantiomeric alkyl-branched pyrrolidine iminosugars - Are specific and potent α-glucosidase inhibitors; Acetone as the sole protecting group. Tetrahedron Letters, 52(2), 219-223. https://doi.org/10.1016/j.tetlet.2010.10.173

@article{221ac4016d914b009a0097fbb121fa8e,

title = "4-C-Me-DAB and 4-C-Me-LAB - Enantiomeric alkyl-branched pyrrolidine iminosugars - Are specific and potent α-glucosidase inhibitors; Acetone as the sole protecting group",

abstract = "The syntheses of 4-C-Me-DAB [1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pKa of the salt around 8.4] is discussed and illustrates the need for care in the analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase Ki 0.89 μM, IC 50 0.41 μM) is a competitive - whereas 4-C-Me-LAB (for rat intestinal sucrase Ki 0.95 μM, IC50 0.66 μM) is a non-competitive - specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB and isoDAB - but not isoLAB - is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.",

author = "Cruz, {Filipa P.Da} and Scott Newberry and Jenkinson, {Sarah F.} and Wormald, {Mark R.} and Butters, {Terry D.} and Alonzi, {Dominic S.} and Shinpei Nakagawa and Frederic Becq and Caroline Norez and Nash, {Robert J.} and Atsushi Kato and Fleet, {George W.J.}",

note = "Funding Information: Financial support [to F.P.C.] provided by the Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia , Portugal is gratefully acknowledged. Part of this work was supported by Grant Number R01CA125642 from the National Cancer Institute (T.D.B., D.S.A.) and by grants from the French association {\textquoteleft}Vaincre la Mucoviscidose{\textquoteright} C.N., F.B.). We thank Dextra Laboratories Limited, Reading, UK for generous gifts of d -erythronolactone and l -erythronolactone.",

year = "2011",

month = jan,

day = "12",

doi = "10.1016/j.tetlet.2010.10.173",

language = "英語",

volume = "52",

pages = "219--223",

journal = "Tetrahedron Letters",

issn = "0040-4039",

publisher = "Elsevier Ltd.",

number = "2",

}

Cruz, FPD, Newberry, S, Jenkinson, SF, Wormald, MR, Butters, TD, Alonzi, DS, Nakagawa, S, Becq, F, Norez, C, Nash, RJ, Kato, A & Fleet, GWJ 2011, '4-C-Me-DAB and 4-C-Me-LAB - Enantiomeric alkyl-branched pyrrolidine iminosugars - Are specific and potent α-glucosidase inhibitors; Acetone as the sole protecting group', Tetrahedron Letters, vol. 52, no. 2, pp. 219-223. https://doi.org/10.1016/j.tetlet.2010.10.173

4-C-Me-DAB and 4-C-Me-LAB - Enantiomeric alkyl-branched pyrrolidine iminosugars - Are specific and potent α-glucosidase inhibitors; Acetone as the sole protecting group. / Cruz, Filipa P.Da; Newberry, Scott; Jenkinson, Sarah F. その他.
In: Tetrahedron Letters, Vol. 52, No. 2, 12.01.2011, p. 219-223.

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

TY - JOUR

T1 - 4-C-Me-DAB and 4-C-Me-LAB - Enantiomeric alkyl-branched pyrrolidine iminosugars - Are specific and potent α-glucosidase inhibitors; Acetone as the sole protecting group

AU - Cruz, Filipa P.Da

AU - Newberry, Scott

AU - Jenkinson, Sarah F.

AU - Wormald, Mark R.

AU - Butters, Terry D.

AU - Alonzi, Dominic S.

AU - Nakagawa, Shinpei

AU - Becq, Frederic

AU - Norez, Caroline

AU - Nash, Robert J.

AU - Kato, Atsushi

AU - Fleet, George W.J.

N1 - Funding Information: Financial support [to F.P.C.] provided by the Fundação para a Ciência e Tecnologia , Portugal is gratefully acknowledged. Part of this work was supported by Grant Number R01CA125642 from the National Cancer Institute (T.D.B., D.S.A.) and by grants from the French association ‘Vaincre la Mucoviscidose’ C.N., F.B.). We thank Dextra Laboratories Limited, Reading, UK for generous gifts of d -erythronolactone and l -erythronolactone.

PY - 2011/1/12

Y1 - 2011/1/12

N2 - The syntheses of 4-C-Me-DAB [1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pKa of the salt around 8.4] is discussed and illustrates the need for care in the analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase Ki 0.89 μM, IC 50 0.41 μM) is a competitive - whereas 4-C-Me-LAB (for rat intestinal sucrase Ki 0.95 μM, IC50 0.66 μM) is a non-competitive - specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB and isoDAB - but not isoLAB - is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.

AB - The syntheses of 4-C-Me-DAB [1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pKa of the salt around 8.4] is discussed and illustrates the need for care in the analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase Ki 0.89 μM, IC 50 0.41 μM) is a competitive - whereas 4-C-Me-LAB (for rat intestinal sucrase Ki 0.95 μM, IC50 0.66 μM) is a non-competitive - specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB and isoDAB - but not isoLAB - is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.

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U2 - 10.1016/j.tetlet.2010.10.173

DO - 10.1016/j.tetlet.2010.10.173

M3 - 学術論文

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AN - SCOPUS:78650022762

SN - 0040-4039

VL - 52

SP - 219

EP - 223

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 2

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