phenyl selenohypobromite

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.68 g (S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)pyrrolidin-2-one (1, R1=pivaloyl) is added to 10 ml toluene. The mixture is then cooled to −15° C. 5.5 ml Lithium bis(trimethylsilyl)amide (1 M in THF) is then added. After 1 h, a mixture of 1.3 g phenyl selenyl bromide in 10 ml toluene is added. After a further 30 min, 100 ml water is added. The phases are separated and the organic phase concentrated in vacuo. The residue is taken up in 25 ml ethyl acetate and then 5.1 ml hydrogen peroxide (37%) is added at room temperature. After 1 h, the phases are separated and the organic phase washed with a saturated sodium hydrogen carbonate solution and then dried (MgSO4). The mixture is concentrated in vacuo and purified by column chromatography, eluting with heptane/ethyl acetate 5:1 to afford (R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-1,5-dihydropyrrol-2-one. 1H NMR (CDCl3): 1.28 (9H), 2.70 (1H), 3.30 (1H), 4.97 (1H), 5.89 (1H), 7.06 (2H), 7.19 (2H), 7.31 (2H), 7.41 (4H). is added After a further 30 min The phases are separated the organic phase concentrated in vacuo 5.1 ml hydrogen peroxide (37%) is added at room temperature After 1 h the phases are separated the organic phase washed with a saturated sodium hydrogen carbonate solution dried (MgSO4) The mixture is concentrated in vacuo purified by column chromatography eluting with heptane/ethyl acetate 5:1

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.68 g (S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)pyrrolidin-2-one (1, R1=pivaloyl) is added to 10 ml toluene. The mixture is then cooled to −15° C. 5.5 ml Lithium bis(trimethylsilyl)amide (1 M in THF) is then added. After 1 h, a mixture of 1.3 g phenyl selenyl bromide in 10 ml toluene is added. After a further 30 min, 100 ml water is added. The phases are separated and the organic phase concentrated in vacuo. The residue is taken up in 25 ml ethyl acetate and then 5.1 ml hydrogen peroxide (37%) is added at room temperature. After 1 h, the phases are separated and the organic phase washed with a saturated sodium hydrogen carbonate solution and then dried (MgSO4). The mixture is concentrated in vacuo and purified by column chromatography, eluting with heptane/ethyl acetate 5:1 to afford (R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-1,5-dihydropyrrol-2-one. 1H NMR (CDCl3): 1.28 (9H), 2.70 (1H), 3.30 (1H), 4.97 (1H), 5.89 (1H), 7.06 (2H), 7.19 (2H), 7.31 (2H), 7.41 (4H). is added After a further 30 min The phases are separated the organic phase concentrated in vacuo 5.1 ml hydrogen peroxide (37%) is added at room temperature After 1 h the phases are separated the organic phase washed with a saturated sodium hydrogen carbonate solution dried (MgSO4) The mixture is concentrated in vacuo purified by column chromatography eluting with heptane/ethyl acetate 5:1

Conditions: temp:39.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-(ethylamino)-1-methyl-1,6-naphthyridin-2(1H)-one (20 mg, 0.1 mmol) and pyridine (27 μL, 0.3 mmol) in DCM (2 mL) was added phenylselenium bromide (72 mg, 0.3 mmol). The mixture was heated at 39° C. for 6 h, and then the solvent was removed under vacuum. The residue was chromatographed on silica gel (30% ethyl acetate in hexanes eluant) to provide the title compound. MS (m/z) 282.0 (M+1). the solvent was removed under vacuum The residue was chromatographed on silica gel (30% ethyl acetate in hexanes eluant)

Conditions: temp:39.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-(ethylamino)-1-methyl-1,6-naphthyridin-2(1H)-one (20 mg, 0.1 mmol) and pyridine (27 μL, 0.3 mmol) in DCM (2 mL) was added phenylselenium bromide (72 mg, 0.3 mmol). The mixture was heated at 39° C. for 6 h, and then the solvent was removed under vacuum. The residue was chromatographed on silica gel (30% ethyl acetate in hexanes eluant) to provide the title compound. MS (m/z) 282.0 (M+1). the solvent was removed under vacuum The residue was chromatographed on silica gel (30% ethyl acetate in hexanes eluant)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Materials. 9-Octadecenoic acid (oleic acid) and its respective methyl ester, methyl-9-octadecenoate was purchased from Nu-Check Prep (Elysian, Minn.). LNO2 and [13C]LNO2 were synthesized as previously described (9,12); OA-NO2 and [13C]OA-NO2 were synthesized as described in below. Phenylselenium bromide, HgCl2, NaNO2, anhydrous tetrahydrofuran (THF), CH3CN, CDCl3, insulin, dexaniethasone and 3-isobutyl-1-methylxantliine were obtained from Sigma/Aldrich (St Louis, Mo.). Silica gel G and HF thin layer chromatography plates (250 and 2000 μm) were from Analtech (Newark, Del.). Methanolic BF3, horseradish peroxidase-linked goat anti-rabbit IgG and Coomasie Blue were from Pierce (Rockford, Ill.). Synthetic solvents were of HPLC grade or better from Fisher Scientific (Fairlawn, N.J.). Solvents used for extractions and mass spectrometric analyses were from Burdick and Jackson (Muskegon, Mich.). [13C]Oleic acid and [13C]linoleic acid were purchased from Cambridge Isotope Laboratories, Inc. (Andover, Mass.). Anti-PPARγ and anti-β-actin antibodies were from Santa Cruz (Santa Cruz, Calif.); anti-aP2 antibody was from Chemicon International Inc. (Temecula, Calif.). Solvents used for extractions and mass spectrometric analyses

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Materials. 9-Octadecenoic acid (oleic acid) and its respective methyl ester, methyl-9-octadecenoate was purchased from Nu-Check Prep (Elysian, Minn.). LNO2 and [13C]LNO2 were synthesized as previously described (9,12); OA-NO2 and [13C]OA-NO2 were synthesized as described in below. Phenylselenium bromide, HgCl2, NaNO2, anhydrous tetrahydrofuran (THF), CH3CN, CDCl3, insulin, dexaniethasone and 3-isobutyl-1-methylxantliine were obtained from Sigma/Aldrich (St Louis, Mo.). Silica gel G and HF thin layer chromatography plates (250 and 2000 μm) were from Analtech (Newark, Del.). Methanolic BF3, horseradish peroxidase-linked goat anti-rabbit IgG and Coomasie Blue were from Pierce (Rockford, Ill.). Synthetic solvents were of HPLC grade or better from Fisher Scientific (Fairlawn, N.J.). Solvents used for extractions and mass spectrometric analyses were from Burdick and Jackson (Muskegon, Mich.). [13C]Oleic acid and [13C]linoleic acid were purchased from Cambridge Isotope Laboratories, Inc. (Andover, Mass.). Anti-PPARγ and anti-β-actin antibodies were from Santa Cruz (Santa Cruz, Calif.); anti-aP2 antibody was from Chemicon International Inc. (Temecula, Calif.). Solvents used for extractions and mass spectrometric analyses

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4 (5 g, 14.1 mmol) in anhydrous THF (50 mL) at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in THF, 15.8 mL, 15.8 mmol) over a period of 10 min. After being stirred at −78° C. for 1 h, Me3SiCl (1.918 g, 17.65 mmol) was added dropwise, and the reaction mixture was allowed to warm to room temperature. After being stirred at room temperature for 30 min, the mixture was cooled to −78° C., and a solution of PhSeBr (5 g, 21.19 mmol) in anhydrous THF (25 mL) was added rapidly. The mixture was diluted with ether (50 mL), washed with water until the color of organic layer changed from dark brown to light yellow, dried (Na2SO4), filtered, and evaporated. The resulting oily residue [containing 3S (α, 5) and 3R (β) isomers; TLC: hexane/EtOAc, 10:1; Rf=0.42 and 0.28, respectively] was purified by flash chromatography on silica gel, eluting with hexane/EtOAc (99:1 to 95:5) to give the title compound 5 as a light yellow oil (4.093 g, 57%). 1H NMR (CDCl3) δ 7.69-7.60 (m, 6H, arom.), 7.46-7.30 (m, 9H, arom.), 4.37-4.34 (m, 1H, H-5), 4.12-4.08 (m, 1H, H-3), 3.86-3.82 (dd, J=3 & 11 Hz, 1H, CH2OH), 3.62-3.59 (dd, J=3 & 11 Hz, 1H, CH2OH), 2.73-2.67 (m, 1H, H-4), 2.32-2.28 (m, 1H, H-4), 1.02 (s, 9H, t-Bu). to warm to room temperature After being stirred at room temperature for 30 min the mixture was cooled to −78° C. washed with water until the color of organic layer dried (Na2SO4) filtered evaporated The resulting oily residue [containing 3S (α, 5) and 3R (β) isomers Rf=0.42 and 0.28, respectively] was purified by flash chromatography on silica gel eluting with hexane/EtOAc (99:1 to 95:5)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4 (5 g, 14.1 mmol) in anhydrous THF (50 mL) at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in THF, 15.8 mL, 15.8 mmol) over a period of 10 min. After being stirred at −78° C. for 1 h, Me3SiCl (1.918 g, 17.65 mmol) was added dropwise, and the reaction mixture was allowed to warm to room temperature. After being stirred at room temperature for 30 min, the mixture was cooled to −78° C., and a solution of PhSeBr (5 g, 21.19 mmol) in anhydrous THF (25 mL) was added rapidly. The mixture was diluted with ether (50 mL), washed with water until the color of organic layer changed from dark brown to light yellow, dried (Na2SO4), filtered, and evaporated. The resulting oily residue [containing 3S (α, 5) and 3R (β) isomers; TLC: hexane/EtOAc, 10:1; Rf=0.42 and 0.28, respectively] was purified by flash chromatography on silica gel, eluting with hexane/EtOAc (99:1 to 95:5) to give the title compound 5 as a light yellow oil (4.093 g, 57%). 1H NMR (CDCl3) δ 7.69-7.60 (m, 6H, arom.), 7.46-7.30 (m, 9H, arom.), 4.37-4.34 (m, 1H, H-5), 4.12-4.08 (m, 1H, H-3), 3.86-3.82 (dd, J=3 & 11 Hz, 1H, CH2OH), 3.62-3.59 (dd, J=3 & 11 Hz, 1H, CH2OH), 2.73-2.67 (m, 1H, H-4), 2.32-2.28 (m, 1H, H-4), 1.02 (s, 9H, t-Bu). to warm to room temperature After being stirred at room temperature for 30 min the mixture was cooled to −78° C. washed with water until the color of organic layer dried (Na2SO4) filtered evaporated The resulting oily residue [containing 3S (α, 5) and 3R (β) isomers Rf=0.42 and 0.28, respectively] was purified by flash chromatography on silica gel eluting with hexane/EtOAc (99:1 to 95:5)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3.3 g of (5Z,13E)-(9α,11α,15S)-9-hydroxy-11,15-bis(tetrahydropyran-2-yloxy)prosta-5,13-dienoic acid methyl ester in 60 ml of tetrahydrofuran was added 610 mg of calcium carbonate at -20° C., and then 6 ml of a solution of benzeneselenenyl bromide in tetrahydrofuran (prepared by adding 0.19 ml of bromine to a solution of 1.25 g of diphenyldiselenide in 6 ml of tetrahydrofuran and stirring the mixture at room temperature for one hour) was added and the reaction mixture was stirred at the same temperature for 10 minutes and further stirred for one hour at 0° C., and then an aqueous solution of ammonium chloride was added. The reaction mixture was extracted with ethyl acetate. The extract was washed with water and an aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate (7:1) as eluent to give 1.62 g of the title compound having the same physical characteristics as hereinbefore described. was added the reaction mixture was stirred at the same temperature for 10 minutes further stirred for one hour at 0° C. The reaction mixture was extracted with ethyl acetate The extract was washed with water an aqueous solution of sodium chloride, dried over magnesium sulphate concentrated under reduced pressure The residue was purified by column chromatography on silica gel using a mixture of cyclohexane and ethyl acetate (7:1) as eluent

Conditions: temp:0.00; pressure:0.00; stir: