克林霉素棕榈酸酯杂质101

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

实验步骤: The preparation of CYC682 described in EP 536936 (see Scheme 1 below) involves reacting cytidine [1] with palmitic anhydride in DMF to form N4-palmitoylcytidine [2] and subsequently protecting with 1,3-dichloro-1,1,4,4-tetraisopropyldisiloxane (CIPS) to form intermediate [3]. Oxidation of [3] with pyridinium dichromate/acetic anhydride in dichloromethane produces intermediate ketone [4], which is then reacted with sodium cyanide and sodium dihydrogen phosphate dihydrate in ethyl acetate to form the cyanohydrin [5]. Intermediate [5] is then reacted with N,N-dimethylaminopyridine, phenoxythiocarbonyl chloride and triethylamine to form intermediate [6], which is subsequently reacted with AIBN and tributyltin hydride in toluene to give intermediate [7]. Deprotection of [7] with acetic acid and tetrabutylammonium fluoride in THF yields the desired product, CYC682.

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

实验步骤: Palmitic acid (512.04 g, 2.00 moles) and acetic anhydride (204.05 g, 2.00 moles) were charged to a two liter reaction flask fitted with an overhead stirrer, thermometer, condenser and nitrogen inlet. The mixture was heated gently with stirring to allow the solid palmitic acid to melt (61° C. to 64° C.). Heating was continued until the reflux temperature had been reached (147° C.), this temperature was maintained for a period of one hour. The resultant mixture was cooled to room temperature to allow a light yellow solid to form, this was slurried in cyclohexane (100 ml), filtered and recrystallised from petroleum ether 60-80. The recrystallised wet solid was placed in a vacuum oven at 40° C. until dry of residual acetic acid. The resultant white powdery solid was stored under vacuum in the presence of silica gel. The yield of palmitic anhydride was 458.49 g which represented a 92.8% chemical yield. fitted with an overhead stirrer The mixture was heated gently (61° C. to 64° C.) Heating (147° C.) this temperature was maintained for a period of one hour to form filtered recrystallised from petroleum ether 60-80 was placed in a vacuum oven at 40° C. until dry of residual acetic acid

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

实验步骤: Palmitic acid (512.04 g, 2.00 moles) and acetic anhydride (204.05 g, 2.00 moles) were charged to a two liter reaction flask fitted with an overhead stirrer, thermometer, condenser and nitrogen inlet. The mixture was heated gently with stirring to allow the solid palmitic acid to melt (61° C. to 64° C.). Heating was continued until the reflux temperature had been reached (147° C.), this temperature was maintained for a period of one hour. The resultant mixture was cooled to room temperature to allow a light yellow solid to form, this was slurried in cyclohexane (100 ml), filtered and recrystallised from petroleum ether 60-80. The recrystallised wet solid was placed in a vacuum oven at 40° C. until dry of residual acetic acid. The resultant white powdery solid was stored under vacuum in the presence of silica gel. The yield of palmitic anhydride was 458.49 g which represented a 92.8% chemical yield. fitted with an overhead stirrer The mixture was heated gently (61° C. to 64° C.) Heating (147° C.) this temperature was maintained for a period of one hour to form filtered recrystallised from petroleum ether 60-80 was placed in a vacuum oven at 40° C. until dry of residual acetic acid

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

实验步骤: Preparation used the same procedure as the platinum cluster conjugate: an estimated 30 nmol of amino-derivatized 2-3 nm palladium cluster, dissolved in 0.6 M triethylammonium bicarbonate in 20% isopropanol/water, was evaporated to dryness five times from methanol, dissolved in 3 mL of dichloromethane, then treated with 200 nmol of palmitic anhydride. The mixture was stirred for one hour at room temperature, washed three times with 0.1 M sodium phosphate buffer at pH 6.5, evaporated to dryness, redissolved in 2:1 methanol/chloroform and separated by gel filtration (GH25, Amicon, eluted with 2:1 methanol:chloroform). After evaporation to dryness, lipid conjugation was demonstrated by extraction of the cluster label into the chloroform layer when the palmitoyl palladium cluster conjugate was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent. Preparation was evaporated to dryness five times from methanol dissolved in 3 mL of dichloromethane washed three times with 0.1 M sodium phosphate buffer at pH 6.5 evaporated to dryness redissolved in 2:1 methanol/chloroform separated by gel filtration (GH25, Amicon eluted with 2:1 methanol After evaporation to dryness, lipid conjugation was demonstrated by extraction of the cluster label into the chloroform layer when the palmitoyl palladium cluster conjugate was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent

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

实验步骤: An estimated 30 nmol of the amino-derivatized 2-3 nm platinum cluster dissolved in 0.6 M triethylammonium bicarbonate in 20% isopropanol/water was evaporated to dryness five times from methanol, then dissolved in 3 mL of diclhoromethane, and treated with 200 nmol of palmitic anhydride. The mixture was stirred for one hour at room temperature, then washed three times with 0.1 M sodium phosphate buffer at pH 6.5. The remaining reaction mixture was evaporated to dryness, redissolved in 2:1 methanol/chloroform, then separated by gel filtration (GH25, Amicon eluted with 2:1 methanol:chloroform); the first species to elute is the dark brown palmitamido-platinum cluster. After evaporation to dryness, lipid conjugation was demonstrated by the extraction of the cluster into the chloroform layer when the palmitoyl cluster was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent. was evaporated to dryness five times from methanol dissolved in 3 mL of diclhoromethane washed three times with 0.1 M sodium phosphate buffer at pH 6.5 The remaining reaction mixture was evaporated to dryness redissolved in 2:1 methanol/chloroform separated by gel filtration (GH25, Amicon eluted with 2:1 methanol the first species to elute After evaporation to dryness, lipid conjugation was demonstrated by the extraction of the cluster into the chloroform layer when the palmitoyl cluster was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent

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

实验步骤: An estimated 30 nmol of the amino-derivatized 2-3 nm platinum cluster dissolved in 0.6 M triethylammonium bicarbonate in 20% isopropanol/water was evaporated to dryness five times from methanol, then dissolved in 3 mL of diclhoromethane, and treated with 200 nmol of palmitic anhydride. The mixture was stirred for one hour at room temperature, then washed three times with 0.1 M sodium phosphate buffer at pH 6.5. The remaining reaction mixture was evaporated to dryness, redissolved in 2:1 methanol/chloroform, then separated by gel filtration (GH25, Amicon eluted with 2:1 methanol:chloroform); the first species to elute is the dark brown palmitamido-platinum cluster. After evaporation to dryness, lipid conjugation was demonstrated by the extraction of the cluster into the chloroform layer when the palmitoyl cluster was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent. was evaporated to dryness five times from methanol dissolved in 3 mL of diclhoromethane washed three times with 0.1 M sodium phosphate buffer at pH 6.5 The remaining reaction mixture was evaporated to dryness redissolved in 2:1 methanol/chloroform separated by gel filtration (GH25, Amicon eluted with 2:1 methanol the first species to elute After evaporation to dryness, lipid conjugation was demonstrated by the extraction of the cluster into the chloroform layer when the palmitoyl cluster was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent

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

实验步骤: The preparation of CYC682 described in EP 536936 (see Scheme 1 below) involves reacting cytidine [1] with palmitic anhydride in DMF to form N4-palmitoylcytidine [2] and subsequently protecting with 1,3-dichloro-1,1,4,4-tetraisopropyldisiloxane (CIPS) to form intermediate [3]. Oxidation of [3] with pyridinium dichromate/acetic anhydride in dichloromethane produces intermediate ketone [4], which is then reacted with sodium cyanide and sodium dihydrogen phosphate dihydrate in ethyl acetate to form the cyanohydrin [5]. Intermediate [5] is then reacted with N,N-dimethylaminopyridine, phenoxythiocarbonyl chloride and triethylamine to form intermediate [6], which is subsequently reacted with AIBN and tributyltin hydride in toluene to give intermediate [7]. Deprotection of [7] with acetic acid and tetrabutylammonium fluoride in THF yields the desired product, CYC682.

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

实验步骤: The preparation of CYC682 described in EP 536936 (see Scheme 1 below) involves reacting cytidine [1] with palmitic anhydride in DMF to form N4-palmitoylcytidine [2] and subsequently protecting with 1,3-dichloro-1,1,4,4-tetraisopropyldisiloxane (CIPS) to form intermediate [3]. Oxidation of [3] with pyridinium dichromate/acetic anhydride in dichloromethane produces intermediate ketone [4], which is then reacted with sodium cyanide and sodium dihydrogen phosphate dihydrate in ethyl acetate to form the cyanohydrin [5]. Intermediate [5] is then reacted with N,N-dimethylaminopyridine, phenoxythiocarbonyl chloride and triethylamine to form intermediate [6], which is subsequently reacted with AIBN and tributyltin hydride in toluene to give intermediate [7]. Deprotection of [7] with acetic acid and tetrabutylammonium fluoride in THF yields the desired product, CYC682.

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

实验步骤: Palmitic acid (512.04 g, 2.00 moles) and acetic anhydride (204.05 g, 2.00 moles) were charged to a two liter reaction flask fitted with an overhead stirrer, thermometer, condenser and nitrogen inlet. The mixture was heated gently with stirring to allow the solid palmitic acid to melt (61° C. to 64° C.). Heating was continued until the reflux temperature had been reached (147° C.), this temperature was maintained for a period of one hour. The resultant mixture was cooled to room temperature to allow a light yellow solid to form, this was slurried in cyclohexane (100 ml), filtered and recrystallised from petroleum ether 60-80. The recrystallised wet solid was placed in a vacuum oven at 40° C. until dry of residual acetic acid. The resultant white powdery solid was stored under vacuum in the presence of silica gel. The yield of palmitic anhydride was 458.49 g which represented a 92.8% chemical yield. fitted with an overhead stirrer The mixture was heated gently (61° C. to 64° C.) Heating (147° C.) this temperature was maintained for a period of one hour to form filtered recrystallised from petroleum ether 60-80 was placed in a vacuum oven at 40° C. until dry of residual acetic acid

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

实验步骤: Preparation used the same procedure as the platinum cluster conjugate: an estimated 30 nmol of amino-derivatized 2-3 nm palladium cluster, dissolved in 0.6 M triethylammonium bicarbonate in 20% isopropanol/water, was evaporated to dryness five times from methanol, dissolved in 3 mL of dichloromethane, then treated with 200 nmol of palmitic anhydride. The mixture was stirred for one hour at room temperature, washed three times with 0.1 M sodium phosphate buffer at pH 6.5, evaporated to dryness, redissolved in 2:1 methanol/chloroform and separated by gel filtration (GH25, Amicon, eluted with 2:1 methanol:chloroform). After evaporation to dryness, lipid conjugation was demonstrated by extraction of the cluster label into the chloroform layer when the palmitoyl palladium cluster conjugate was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent. Preparation was evaporated to dryness five times from methanol dissolved in 3 mL of dichloromethane washed three times with 0.1 M sodium phosphate buffer at pH 6.5 evaporated to dryness redissolved in 2:1 methanol/chloroform separated by gel filtration (GH25, Amicon eluted with 2:1 methanol After evaporation to dryness, lipid conjugation was demonstrated by extraction of the cluster label into the chloroform layer when the palmitoyl palladium cluster conjugate was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent

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

实验步骤: Preparation used the same procedure as the platinum cluster conjugate: an estimated 30 nmol of amino-derivatized 2-3 nm palladium cluster, dissolved in 0.6 M triethylammonium bicarbonate in 20% isopropanol/water, was evaporated to dryness five times from methanol, dissolved in 3 mL of dichloromethane, then treated with 200 nmol of palmitic anhydride. The mixture was stirred for one hour at room temperature, washed three times with 0.1 M sodium phosphate buffer at pH 6.5, evaporated to dryness, redissolved in 2:1 methanol/chloroform and separated by gel filtration (GH25, Amicon, eluted with 2:1 methanol:chloroform). After evaporation to dryness, lipid conjugation was demonstrated by extraction of the cluster label into the chloroform layer when the palmitoyl palladium cluster conjugate was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent. Preparation was evaporated to dryness five times from methanol dissolved in 3 mL of dichloromethane washed three times with 0.1 M sodium phosphate buffer at pH 6.5 evaporated to dryness redissolved in 2:1 methanol/chloroform separated by gel filtration (GH25, Amicon eluted with 2:1 methanol After evaporation to dryness, lipid conjugation was demonstrated by extraction of the cluster label into the chloroform layer when the palmitoyl palladium cluster conjugate was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent

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

实验步骤: An estimated 30 nmol of the amino-derivatized 2-3 nm platinum cluster dissolved in 0.6 M triethylammonium bicarbonate in 20% isopropanol/water was evaporated to dryness five times from methanol, then dissolved in 3 mL of diclhoromethane, and treated with 200 nmol of palmitic anhydride. The mixture was stirred for one hour at room temperature, then washed three times with 0.1 M sodium phosphate buffer at pH 6.5. The remaining reaction mixture was evaporated to dryness, redissolved in 2:1 methanol/chloroform, then separated by gel filtration (GH25, Amicon eluted with 2:1 methanol:chloroform); the first species to elute is the dark brown palmitamido-platinum cluster. After evaporation to dryness, lipid conjugation was demonstrated by the extraction of the cluster into the chloroform layer when the palmitoyl cluster was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent. was evaporated to dryness five times from methanol dissolved in 3 mL of diclhoromethane washed three times with 0.1 M sodium phosphate buffer at pH 6.5 The remaining reaction mixture was evaporated to dryness redissolved in 2:1 methanol/chloroform separated by gel filtration (GH25, Amicon eluted with 2:1 methanol the first species to elute After evaporation to dryness, lipid conjugation was demonstrated by the extraction of the cluster into the chloroform layer when the palmitoyl cluster was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent