Total Syntheses of Casuarine and Its 6-O-alpha-Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families

Francesca Cardona; Camilla Parmeggiani; Enrico Faggi; Claudia Bonaccini; Paola Gratteri; Lyann Sim; Tracey M. Gloster; Shirley Roberts; Gideon J. Davies; David R. Rose; Andrea Goti

doi:10.1002/chem.200801578

Total Syntheses of Casuarine and Its 6-O-alpha-Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families

Francesca Cardona, Camilla Parmeggiani, Enrico Faggi, Claudia Bonaccini, Paola Gratteri, Lyann Sim, Tracey M. Gloster, Shirley Roberts, Gideon J. Davies, David R. Rose, Andrea Goti

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-alpha-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao-Fleming oxidation and selective alpha-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.

Original language	English
Pages (from-to)	1627-1636
Number of pages	10
Journal	Chemistry - A European Journal
Volume	15
Issue number	7
DOIs	https://doi.org/10.1002/chem.200801578
Publication status	Published - 2 Feb 2009

Keywords

enzyme structures
maltase glucoamylase
natural products
total synthesis
trehalase
INTESTINAL MALTASE-GLUCOAMYLASE
HYDROXY GROUP
POLYHYDROXYLATED PYRROLIZIDINES
STEREOSELECTIVE-SYNTHESIS
PHENYLDIMETHYLSILYL GROUP
SILAFUNCTIONAL COMPOUNDS
ASYMMETRIC SYNTHESES
ENZYMATIC-SYNTHESIS
SUCRASE-ISOMALTASE
ORGANIC-SYNTHESIS

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Cardona, F., Parmeggiani, C., Faggi, E., Bonaccini, C., Gratteri, P., Sim, L., Gloster, T. M., Roberts, S., Davies, G. J., Rose, D. R., & Goti, A. (2009). Total Syntheses of Casuarine and Its 6-O-alpha-Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families. Chemistry - A European Journal, 15(7), 1627-1636. https://doi.org/10.1002/chem.200801578

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title = "Total Syntheses of Casuarine and Its 6-O-alpha-Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families",

abstract = "Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-alpha-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao-Fleming oxidation and selective alpha-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.",

keywords = "enzyme structures, maltase glucoamylase, natural products, total synthesis, trehalase, INTESTINAL MALTASE-GLUCOAMYLASE, HYDROXY GROUP, POLYHYDROXYLATED PYRROLIZIDINES, STEREOSELECTIVE-SYNTHESIS, PHENYLDIMETHYLSILYL GROUP, SILAFUNCTIONAL COMPOUNDS, ASYMMETRIC SYNTHESES, ENZYMATIC-SYNTHESIS, SUCRASE-ISOMALTASE, ORGANIC-SYNTHESIS",

author = "Francesca Cardona and Camilla Parmeggiani and Enrico Faggi and Claudia Bonaccini and Paola Gratteri and Lyann Sim and Gloster, {Tracey M.} and Shirley Roberts and Davies, {Gideon J.} and Rose, {David R.} and Andrea Goti",

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doi = "10.1002/chem.200801578",

language = "English",

volume = "15",

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issn = "0947-6539",

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Cardona, F, Parmeggiani, C, Faggi, E, Bonaccini, C, Gratteri, P, Sim, L, Gloster, TM, Roberts, S, Davies, GJ, Rose, DR & Goti, A 2009, 'Total Syntheses of Casuarine and Its 6-O-alpha-Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families', Chemistry - A European Journal, vol. 15, no. 7, pp. 1627-1636. https://doi.org/10.1002/chem.200801578

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AU - Cardona, Francesca

AU - Parmeggiani, Camilla

AU - Faggi, Enrico

AU - Bonaccini, Claudia

AU - Gratteri, Paola

AU - Sim, Lyann

AU - Gloster, Tracey M.

AU - Roberts, Shirley

AU - Davies, Gideon J.

AU - Rose, David R.

AU - Goti, Andrea

PY - 2009/2/2

Y1 - 2009/2/2

N2 - Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-alpha-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao-Fleming oxidation and selective alpha-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.

AB - Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-alpha-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao-Fleming oxidation and selective alpha-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.

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KW - maltase glucoamylase

KW - natural products

KW - total synthesis

KW - trehalase

KW - INTESTINAL MALTASE-GLUCOAMYLASE

KW - HYDROXY GROUP

KW - POLYHYDROXYLATED PYRROLIZIDINES

KW - STEREOSELECTIVE-SYNTHESIS

KW - PHENYLDIMETHYLSILYL GROUP

KW - SILAFUNCTIONAL COMPOUNDS

KW - ASYMMETRIC SYNTHESES

KW - ENZYMATIC-SYNTHESIS

KW - SUCRASE-ISOMALTASE

KW - ORGANIC-SYNTHESIS

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DO - 10.1002/chem.200801578

M3 - Article

SN - 0947-6539

VL - 15

SP - 1627

EP - 1636

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 7

ER -

Total Syntheses of Casuarine and Its 6-O-alpha-Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families

Abstract

Keywords

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