11-iodoundec-1-ene

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: t-BuOK (3.6 g, 0.032 mole) was dissolved in 250 ml of dry benzene at 40°-50° C. To the stirred solution was added 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene (3.6 g, 0.016 mole) in 50 ml of dry benzene and then, 10-undecenyl iodide (4.58 g, 0.016 mole) at 30° C. under N2. The mixture was heated to 60° C. for 2.5 hr under N2. After cooling the reaction mixture to room temperature, water was added. The whole mixture was extracted twice with diethylether. The combined diethylether solution was dried over anhydrous MgSO4 and then concentrated. Flash column chromatography of the residue on silica gel afforded 6,7-Dimethyl-4-oxo-3-(10-undecenyl)-1,2,3,4-tetrahydrophenanthrene as a sticky brown solid (2.36 g, 0.0063 mole, 39% yield) as a desired product, and unreacted 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene (1.70 g, 47% recovered). 1H NMR (CDCl3)δ 1.29-1.62 (m,14H), 1.86-2.08 (m,4H), 2.21-2.35 (m,2H), 2.40 (s,3H), 2.46 (s,3H), 2.52-2.63 (m,1H), 3.07-3.13 (m,2H), 4.90-5.04 (m,2H), 5.75-5.89 (m,1H), 7.17 (d, J=8.2 Hz,1H), 7.53 (s,1H), 7.77 (d, J=8.2 Hz,1H), 9.10 (s,1H), IR (KBr) cm-1 2920, 2850, 1669, 1600, exact (EI) mass. calcd. for C27H36O: 376.2766, Found: 376.2766. at 30° C. After cooling the reaction mixture to room temperature The whole mixture was extracted twice with diethylether The combined diethylether solution was dried over anhydrous MgSO4 concentrated

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a glass screw top jar were added undecylenyl iodide (5 grams), toluene solvent (30 grams) and eicosene (5 grams, Aldrich Chemical). Under argon atmosphere were added diethyl aluminum chloride (10 milliliters of a 1.8 molar solution in toluene) and 0.5 teaspoon of TiCl3 --AA (available from Alfa, about 2 grams). Two additional charges of both catalysts were added in 90 minute intervals and then the reaction mixture was stirred for 16 hours at 25° C. Methanol was added and the mixture was precipitated into methanol/hydrochloric acid using a Waring blender. The solids were sequentially washed with methanol, water and then methanol using a blender and the residue was isolated by filtration and dried in vacuo to yield 6.26 grams of the grey rubbery product, poly(undecylenyl iodide-eicosene) copolymer. 13C NMR (in deuterated chloroform) analysis measured a ratio of CH2 --I groups to CH3 groups present to be 31 weight percent. Two additional charges of both catalysts were added in 90 minute intervals the mixture was precipitated into methanol/hydrochloric acid using a Waring blender The solids were sequentially washed with methanol, water methanol using a blender and the residue was isolated by filtration dried in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a glass screw top jar were added undecylenyl iodide (6.3 grams), toluene solvent (63.1 grams), and eicosene (18.73 grams). Under argon atmosphere were added diethyl aluminum chloride (25 milliliters of a 1.8 molar solution in toluene) and 1.25 teaspoons of TiCl3 --AA (available from Alfa, about 5 grams). The sealed jar was stirred for 2 hours. Methanol was added dropwise until the mixture turned green. The reaction mixture was then added to methanol/hydrochloric acid in a Waring blender to precipitate the solid polymer. In the blender, the polymer was washed successively with methanol, water and then methanol. After filtration, the isolated polymer was dried in vacuo to yield 21.04 grams of the semicrystalline polymer product, poly(undecylenyl iodide-eicosene) copolymer, the DSC of this product indicated two semicrystalline endotherms at 30° and 55° C. Solid state 13C NMR analysis measured 17 weight percent of CH2 --I groups present. to precipitate the solid polymer In the blender, the polymer was washed successively with methanol, water After filtration the isolated polymer was dried in vacuo

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: t-BuOK (3.6 g, 0.032 mole) was dissolved in 250 ml of dry benzene at 40°-50° C. To the stirred solution was added 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene (3.6 g, 0.016 mole) in 50 ml of dry benzene and then, 10-undecenyl iodide (4.58 g, 0.016 mole) at 30° C. under N2. The mixture was heated to 60° C. for 2.5 hr under N2. After cooling the reaction mixture to room temperature, water was added. The whole mixture was extracted twice with diethylether. The combined diethylether solution was dried over anhydrous MgSO4 and then concentrated. Flash column chromatography of the residue on silica gel afforded 6,7-Dimethyl-4-oxo-3-(10-undecenyl)-1,2,3,4-tetrahydrophenanthrene as a sticky brown solid (2.36 g, 0.0063 mole, 39% yield) as a desired product, and unreacted 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene (1.70 g, 47% recovered). 1H NMR (CDCl3) δ 1.29-1.62 (m,14H), 1.86-2.08 (m,4H), 2.21-2.35 (m,2H), 2.40 (s,3H), 2.46 (s,3H), 2.52-2.63 (m,1H), 3.07-3.13 (m,2H), 4.90-5.04 (m,2H), 5.75-5.89 (m,1H), 7.17 (d, J=8.2 Hz,1H), 7.53 (s,1H), 7.77 (d, J=8.2 Hz,1H), 9.10 (s,1H), IR (KBr) cm-1 2920, 2850, 1669, 1600, exact (EI) mass. calcd. for C27H36O: 376.2766, Found: 376.2766. at 30° C. After cooling the reaction mixture to room temperature The whole mixture was extracted twice with diethylether The combined diethylether solution was dried over anhydrous MgSO4 concentrated

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: t-BuOK (3.6 g, 0.032 mole) was dissolved in 250 ml of dry benzene at 40°-50° C. To the stirred solution was added 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene (3.6 g, 0.016 mole) in 50 ml of dry benzene and then, 10-undecenyl iodide (4.58 g, 0.016 mole) at 30° C. under N2. The mixture was heated to 60° C. for 2.5 hr under N2. After cooling the reaction mixture to room temperature, water was added. The whole mixture was extracted twice with diethylether. The combined diethylether solution was dried over anhydrous MgSO4 and then concentrated. Flash column chromatography of the residue on silica gel afforded 6,7-Dimethyl-4-oxo-3-(10-undecenyl)-1,2,3,4-tetrahydrophenanthrene as a sticky brown solid (2.36 g, 0.0063 mole, 39% yield) as a desired product, and unreacted 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene (1.70 g, 47% recovered). 1H NMR (CDCl3) δ 1.29-1.62 (m,14H), 1.86-2.08 (m,4H), 2.21-2.35 (m,2H), 2.40 (s,3H), 2.46 (s,3H), 2.52-2.63 (m,1H), 3.07-3.13 (m,2H), 4.90-5.04 (m,2H), 5.75-5.89 (m,1H), 7.17 (d, J=8.2 Hz,1H), 7.53 (s,1H), 7.77 (d, J=8.2 Hz,1H), 9.10 (s,1H), IR (KBr) cm-1 2920, 2850, 1669, 1600, exact (EI) mass. calcd. for C27H36O: 376.2766, Found: 376.2766. at 30° C. After cooling the reaction mixture to room temperature The whole mixture was extracted twice with diethylether The combined diethylether solution was dried over anhydrous MgSO4 concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A first generation FP probe, FP-biotin, possessed a linear decamethylene chain connecting its FP reactive group to 5-(biotinamido)-pentylamine through an amide bond (15). A variant of FP-biotin in which the agent's decamethylene chain was replaced by a more hydrophilic tetraethylene glycol linker was synthesized. Briefly, tetraethyleneglycol (1) was monosilyated to provide compound 2, which following conversion to alkyl iodide 3, was reacted with triethylphosphite to give phosphonate 4. Desilyation of 4 with HF-pyridine, followed by treatment with N,N-disuccinimidyl carbonate, provided NHS-carbonate 6. Compound 6 was converted to monoethoxy phosphonate acid 7 by treatment with oxalyl chloride followed by hydrolytic workup. Compound 7 was treated with DAST to give fluorophosphonate 8, which was then coupled to 5-(biotinamido)pentylamine (Pierce) to provide FP-peg-biotin (9).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10-undecen-1-ol (1)(numbering from Scheme 1) was converted to iodinated compound 3 through a tosylate intermediate (2). Reaction of 3 with excess triethylphosphite under reflux conditions afforded the diethoxy phosphonate 4, which was converted to the ethoxyhydroxy phosphonate 5 by treatment with trimethylsilylbromide (TMSBr). The double bond of 6 was oxidatively cleaved with ruthenium trichloride and sodium periodate (Carlsen, et al. (1981) J. Org. Chem. 46, 3k936-3938) to yield the terminal carboxylic acid product 6. Treatment of 6 with excess diethylaminosulfur trifluoride (DAST) and N-hydoxysuccinimide (NHS) afforded an N-succinyl fluorophosphonate intermediate which was reacted with 5-(biotinamido) pentylamine (NH2-biotin) to generate FP-biotin (7). This synthetic route also allowed for the facile coupling of 6 to other reporter groups, including fluorescein cadaverine, which generated a fluorescent fluorophosphonate, FP-fluorescein [8; MALDI-FTMS (DHB) m/z 778.2671 (C38H47FN3O8PS+Na+ requires 778.2703)].

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Triethylphosphite (12.2 mL, 71 mmol, 10 equiv) was added to 3 (2.0 g, 7.1 mmol, 1.0 equiv) and the mixture was stirred at reflux for 15 h. The excess triethylphosphite was removed by distillation and the remaining residue submitted to flash chromatography (SiO2, 5×15 cm, 25-50% ethyl acetate-hexanes gradient elution) to afford 4 (1.30 g, 2.1 g theoretical, 62%) as a colorless oil: 1H NMR (CDCl3, 250 MHz) δ 5.95-5.75 (m, 1H, RCH═CH2), 5.03-4.90 (m, 2H, RCH═CH2), 4.05 (m, 4H, CH3CH2OP), 2.02 (m, 2H, CH2CH═CH2), 1.80-1.20 (m, 20H); MALDI-FTMS (DHB) m/z 291.2088 (C15H31O3P+H+ requires 291.2089). at reflux for 15 h The excess triethylphosphite was removed by distillation the remaining residue submitted to flash chromatography (SiO2, 5×15 cm, 25-50% ethyl acetate-hexanes gradient elution) to afford 4 (1.30 g, 2.1 g theoretical, 62%) as a colorless oil

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Triethylphosphite (12.2 mL, 71 mmol, 10 equiv) was added to 3 (2.0 g, 7.1 mmol, 1.0 equiv) and the mixture was stirred at reflux for 15 h. The excess triethylphosphite was removed by distillation and the remaining residue submitted to flash chromatography (SiO2, 5×15 cm, 25-50% ethyl acetate-hexanes gradient elution) to afford 4 (1.30 g, 2.1 g theoretical, 62%) as a colorless oil: 1H NMR (CDCl3, 250 MHz) δ 5.95-5.75 (m, 1H, RCH═CH2), 5.03-4.90 (m, 2H, RCH═CH2), 4.05 (m, 4H, CH3CH2OP), 2.02 (m, 2H, CH2CH═CH2), 1.80-1.20 (m, 20H); MALDI-FTMS (DHB) m/z 291.2088 (C15H31O3P+H+ requires 291.2089). at reflux for 15 h The excess triethylphosphite was removed by distillation the remaining residue submitted to flash chromatography (SiO2, 5×15 cm, 25-50% ethyl acetate-hexanes gradient elution) to afford 4 (1.30 g, 2.1 g theoretical, 62%) as a colorless oil

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: t-BuOK (3.6 g, 0.032 mole) was dissolved in 250 ml of dry benzene at 40°-50° C. To the stirred solution was added 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene (3.6 g, 0.016 mole) in 50 ml of dry benzene and then, 10-undecenyl iodide (4.58 g, 0.016 mole) at 30° C. under N2. The mixture was heated to 60° C. for 2.5 hr under N2. After cooling the reaction mixture to room temperature, water was added. The whole mixture was extracted twice with diethylether. The combined diethylether solution was dried over anhydrous MgSO4 and then concentrated. Flash column chromatography of the residue on silica gel afforded 6,7-Dimethyl-4-oxo-3-(10-undecenyl)-1,2,3,4-tetrahydrophenanthrene as a sticky brown solid (2.36 g, 0.0063 mole, 39% yield) as a desired product, and unreacted 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene (1.70 g, 47% recovered). 1H NMR (CDCl3)δ 1.29-1.62 (m,14H), 1.86-2.08 (m,4H), 2.21-2.35 (m,2H), 2.40 (s,3H), 2.46 (s,3H), 2.52-2.63 (m,1H), 3.07-3.13 (m,2H), 4.90-5.04 (m,2H), 5.75-5.89 (m,1H), 7.17 (d, J=8.2 Hz,1H), 7.53 (s,1H), 7.77 (d, J=8.2 Hz,1H), 9.10 (s,1H), IR (KBr) cm-1 2920, 2850, 1669, 1600, exact (EI) mass. calcd. for C27H36O: 376.2766, Found: 376.2766. at 30° C. After cooling the reaction mixture to room temperature The whole mixture was extracted twice with diethylether The combined diethylether solution was dried over anhydrous MgSO4 concentrated

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a glass screw top jar were added undecylenyl iodide (5 grams), toluene solvent (30 grams) and eicosene (5 grams, Aldrich Chemical). Under argon atmosphere were added diethyl aluminum chloride (10 milliliters of a 1.8 molar solution in toluene) and 0.5 teaspoon of TiCl3 --AA (available from Alfa, about 2 grams). Two additional charges of both catalysts were added in 90 minute intervals and then the reaction mixture was stirred for 16 hours at 25° C. Methanol was added and the mixture was precipitated into methanol/hydrochloric acid using a Waring blender. The solids were sequentially washed with methanol, water and then methanol using a blender and the residue was isolated by filtration and dried in vacuo to yield 6.26 grams of the grey rubbery product, poly(undecylenyl iodide-eicosene) copolymer. 13C NMR (in deuterated chloroform) analysis measured a ratio of CH2 --I groups to CH3 groups present to be 31 weight percent. Two additional charges of both catalysts were added in 90 minute intervals the mixture was precipitated into methanol/hydrochloric acid using a Waring blender The solids were sequentially washed with methanol, water methanol using a blender and the residue was isolated by filtration dried in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a glass screw top jar were added undecylenyl iodide (6.3 grams), toluene solvent (63.1 grams), and eicosene (18.73 grams). Under argon atmosphere were added diethyl aluminum chloride (25 milliliters of a 1.8 molar solution in toluene) and 1.25 teaspoons of TiCl3 --AA (available from Alfa, about 5 grams). The sealed jar was stirred for 2 hours. Methanol was added dropwise until the mixture turned green. The reaction mixture was then added to methanol/hydrochloric acid in a Waring blender to precipitate the solid polymer. In the blender, the polymer was washed successively with methanol, water and then methanol. After filtration, the isolated polymer was dried in vacuo to yield 21.04 grams of the semicrystalline polymer product, poly(undecylenyl iodide-eicosene) copolymer, the DSC of this product indicated two semicrystalline endotherms at 30° and 55° C. Solid state 13C NMR analysis measured 17 weight percent of CH2 --I groups present. to precipitate the solid polymer In the blender, the polymer was washed successively with methanol, water After filtration the isolated polymer was dried in vacuo