Mechanism of the hydrolysis of the sulfamate EMATE-an irreversible steroid sulfatase inhibitor

William J. Spillane; Jean Baptiste Malaubier

doi:10.1016/j.tetlet.2010.02.065

Mechanism of the hydrolysis of the sulfamate EMATE-an irreversible steroid sulfatase inhibitor

William J. Spillane, Jean Baptiste Malaubier

Cellular & Molecular Medicine

University of Galway

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

10 Citations (Scopus)

Abstract

The kinetics of hydrolysis of the medicinally important sulfamate ester EMATE have been probed over a wide pH range and into moderately strong base (H_ region). Analysis of the pH/H_-rate profile, measurements of pK_as, solvent-reactivity, kinetic isotope effects and determination of activation data reveal that in the pH range from ∼1 to ∼8 an S_N2 (S) solvolytic mechanism is followed and after the pK_a of EMATE (pK_a ∼9) is passed, a second pathway showing a first-order dependence on base operates and an E1cB mechanism is supported.

Original language	English
Pages (from-to)	2059-2062
Number of pages	4
Journal	Tetrahedron Letters
Volume	51
Issue number	15
DOIs	https://doi.org/10.1016/j.tetlet.2010.02.065
Publication status	Published - 14 Apr 2010

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Authors
Spillane, WJ,Malaubier, JB

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10.1016/j.tetlet.2010.02.065

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title = "Mechanism of the hydrolysis of the sulfamate EMATE-an irreversible steroid sulfatase inhibitor",

abstract = "The kinetics of hydrolysis of the medicinally important sulfamate ester EMATE have been probed over a wide pH range and into moderately strong base (H\_ region). Analysis of the pH/H\_-rate profile, measurements of pKas, solvent-reactivity, kinetic isotope effects and determination of activation data reveal that in the pH range from ∼1 to ∼8 an SN2 (S) solvolytic mechanism is followed and after the pKa of EMATE (pKa ∼9) is passed, a second pathway showing a first-order dependence on base operates and an E1cB mechanism is supported.",

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T1 - Mechanism of the hydrolysis of the sulfamate EMATE-an irreversible steroid sulfatase inhibitor

AU - Spillane, William J.

AU - Malaubier, Jean Baptiste

PY - 2010/4/14

Y1 - 2010/4/14

N2 - The kinetics of hydrolysis of the medicinally important sulfamate ester EMATE have been probed over a wide pH range and into moderately strong base (H_ region). Analysis of the pH/H_-rate profile, measurements of pKas, solvent-reactivity, kinetic isotope effects and determination of activation data reveal that in the pH range from ∼1 to ∼8 an SN2 (S) solvolytic mechanism is followed and after the pKa of EMATE (pKa ∼9) is passed, a second pathway showing a first-order dependence on base operates and an E1cB mechanism is supported.

AB - The kinetics of hydrolysis of the medicinally important sulfamate ester EMATE have been probed over a wide pH range and into moderately strong base (H_ region). Analysis of the pH/H_-rate profile, measurements of pKas, solvent-reactivity, kinetic isotope effects and determination of activation data reveal that in the pH range from ∼1 to ∼8 an SN2 (S) solvolytic mechanism is followed and after the pKa of EMATE (pKa ∼9) is passed, a second pathway showing a first-order dependence on base operates and an E1cB mechanism is supported.

UR - https://www.scopus.com/pages/publications/77649271170

U2 - 10.1016/j.tetlet.2010.02.065

DO - 10.1016/j.tetlet.2010.02.065

M3 - Article

SN - 0040-4039

VL - 51

SP - 2059

EP - 2062

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 15

ER -

Mechanism of the hydrolysis of the sulfamate EMATE-an irreversible steroid sulfatase inhibitor

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