Introduction of 2,2,2‐Trichloroethyl‐Protected Sulfates into Monosaccharides with a Sulfuryl Imidazolium Salt and Application to the Synthesis of Sulfated Carbohydrates

Ingram, Laura J.; Taylor, Scott D.

doi:10.1002/anie.200600153

Cited by 56 publications

(38 citation statements)

References 11 publications

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“…Afterward, the sample was dried under nitrogen and stored overnight in a vacuum desiccator over phosphorus pentoxide to afford a white solid (15.3 mg, 97% yield Synthesis of N-desTAM-S Ammonium Salt. The sulfamate of N-desTAM was prepared using sulfuryl imidazolium triflate (2,2,2-trichloroethoxysulfuryl-(2-methyl)-N-methy-limidazolium trifate) as the sulfating reagent, and the synthesis of this reagent has been previously reported elsewhere (Ingram and Taylor, 2006;Desoky et al, 2011). We added 1,2-dimethylimidazole (14 ml, 157 mmol) to a solution of N-desTAM (28 mg, 69 mmol) and sulfuryl imidazolium triflate (94 mg, 207 mmol) dissolved in dichloromethane (5 ml).…”

Section: Methodsmentioning

confidence: 99%

Endoxifen and Other Metabolites of Tamoxifen Inhibit Human Hydroxysteroid Sulfotransferase 2A1 (hSULT2A1)

2014

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Although tamoxifen is a successful agent for treatment and prevention of estrogen-dependent breast cancer, its use has been limited by the low incidence of endometrial cancer. Human hydroxysteroid sulfotransferase 2A1 (hSULT2A1) catalyzes the formation of an a-sulfooxy metabolite of tamoxifen that is reactive toward DNA, and this has been implicated in its carcinogenicity. Also, hSULT2A1 functions in the metabolism of steroid hormones such as dehydroepiandrosterone (DHEA) and pregnenolone (PREG). These roles of hSULT2A1 in steroid hormone metabolism and in generating a reactive metabolite of tamoxifen led us to examine its interactions with tamoxifen and several of its major metabolites. We hypothesized that metabolites of tamoxifen may regulate the catalytic activity of hSULT2A1, either through direct inhibition or through serving as alternate substrates for the enzyme. We found that 4-hydroxy-N-desmethyltamoxifen (endoxifen) is a potent inhibitor of hSULT2A1-catalyzed sulfation of PREG and DHEA, with K i values of 3.5 and 2.8 mM, respectively. In the hSULT2A1-catalyzed sulfation of PREG, 4-hydroxytamoxifen (4-OHTAM) and N-desmethyltamoxifen (N-desTAM) exhibited K i values of 12.7 and 9.8 mM, respectively, whereas corresponding K i values of 19.4 and 17.2 mM were observed with DHEA as substrate. A K i value of 9.1 mM was observed for tamoxifen-N-oxide with DHEA as substrate, and this increased to 16.9 mM for the hSULT2A1-catalyzed sulfation of PREG. Three metabolites were substrates for hSULT2A1, with relative sulfation rates of 4-OHTAM > N-desTAM > > endoxifen. These results may be useful in interpreting ongoing clinical trials of endoxifen and in improving the design of related molecules.

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Section: Methodsmentioning

confidence: 99%

Endoxifen and Other Metabolites of Tamoxifen Inhibit Human Hydroxysteroid Sulfotransferase 2A1 (hSULT2A1)

2014

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“…TCECS reaction with diisopropylidene-D-glucose gave the corresponding chlorosugar under a variety of different conditions 74. To obviate the chlorosugar product, sulfuryl imidazolium triflate was chosen as a sulfating agent.…”

Section: Chemical Sulfation Approachesmentioning

confidence: 99%

Chemical sulfation of small molecules—advances and challenges

2010

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“…Representative Procedure for the Selective Sulfation of Compounds 3-7, [12][13][14][15]17, and 18 (Table 1, compound 7). Method A: Reagent 2 (1.5 g, 3.32 mmol) and DMI (0.38 g, 3.98 mmol) were added in one portion to a solution of carbohydrate 7 32 in CH 2 Cl 2 (4 mL) at 0°C (ice bath).…”

Section: Methodsmentioning

confidence: 99%

“…15,16 The resulting sulfated products are stable to many of the conditions that are commonly encountered during carbohydrate syntheses, and the sulfate group is readily deprotected in excellent yield using mild reducing conditions such as Zn-ammonium formate or Pd/C and ammonium formate. 15,16 Regioselective incorporation of protecting groups is one tactic that is employed to minimize the number of synthetic operations during the synthesis of carbohydrates. 17 There are numerous examples of the regioselective incorporation of unprotected sulfate groups into carbohydrates either directly by reacting glycosides sulfur trioxide adducts or, more commonly, reacting stannanediyl acetals or stannyl ethers of glycosides with sulfur trioxide adducts.…”

Section: Introductionmentioning

confidence: 99%

“…15 TCEprotected sulfate esters can be readily introduced into carbohydrates using sulfuryl imidazolium salts 1 or 2 (Scheme 1). 15,16 The resulting sulfated products are stable to many of the conditions that are commonly encountered during carbohydrate syntheses, and the sulfate group is readily deprotected in excellent yield using mild reducing conditions such as Zn-ammonium formate or Pd/C and ammonium formate. 15,16 Regioselective incorporation of protecting groups is one tactic that is employed to minimize the number of synthetic operations during the synthesis of carbohydrates.…”

Section: Introductionmentioning

confidence: 99%

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Multiple and Regioselective Introduction of Protected Sulfates into Carbohydrates Using Sulfuryl Imidazolium Salts

Desoky

Taylor

2009

J. Org. Chem.

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Selective incorporation of trichloroethyl (TCE)-protected sulfates into monosaccharides was examined using reagent 2. In general, sulfation of 4,6-O-benzylidene acetals of galactosides and glucosides (2-OH versus 3-OH sulfations) proceeded in good to excellent yield and selectivity. Sulfation occurred predominantly at the 2-OH in 4,6-O-benzylidene acetals of alpha-glucosides and at the 3-OH in 4,6-O-benzylidene acetals of beta-galactosides and beta-glucosides. Good yields and selectivity was also achieved for the 3-OH in 3,4-diols of glucosides and galactosides. A glucoside bearing a 2-amino moiety and 6-OH group gave mainly the N-sulfated product in good yield. Selective sulfation of the primary 6-OH in galactose and glucose derivatives bearing one or two free secondary hydroxyl groups was also achieved usually in good yield and selectivity. Reagent 2 was also effective for the direct disulfation of diols of glucosides and galactosides, and trisulfated monosaccharides could be prepared from the disulfated compounds.

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Introduction of 2,2,2‐Trichloroethyl‐Protected Sulfates into Monosaccharides with a Sulfuryl Imidazolium Salt and Application to the Synthesis of Sulfated Carbohydrates

Abstract: Scheme 4. Glycosylation and TCE cleavage. M.S. = molecular sieves. Angewandte Chemie 3505

Cited by 56 publications

References 11 publications

Endoxifen and Other Metabolites of Tamoxifen Inhibit Human Hydroxysteroid Sulfotransferase 2A1 (hSULT2A1)

Endoxifen and Other Metabolites of Tamoxifen Inhibit Human Hydroxysteroid Sulfotransferase 2A1 (hSULT2A1)

Chemical sulfation of small molecules—advances and challenges

Multiple and Regioselective Introduction of Protected Sulfates into Carbohydrates Using Sulfuryl Imidazolium Salts

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