oxacycloundecane-2,11-dione

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

Procedure: BTCA was reacted with two equivalents of methoxy PEG amine in refluxing THF for 5 hours to yield dimethoxy-PEG tetracarboxybenzoate, with two remaining carboxylic groups. The PEG-dimer was reacted with acetic anhydride and then with sebacic anhydride to form the tetra-armed diblock PEG2 -benzene-PSA2. to yield dimethoxy-PEG tetracarboxybenzoate

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

Procedure: To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere, was added the previously made Oxacycloundecane-2,11-dione (37.95 g, 206 mmol), 1,4-diacetoxy-benzene (20 g, 103 mmol), and 200 mL carbon disulfide. Aluminum (III) trichloride (68.7 g, 515 mmol) was added and the reaction stirred for 72 hours. Carbon disulfide was decanted away, and ice was carefully added until most of mixture was dissolved. The insoluble material was collected by suction filtration and washed with 2×100 mL of water. The solid was then dissolved in 50 mL of 1 M aqueous sodium hydroxide and stirred for 1 hour. The solution was acidified with 1 M aqueous hydrochloric acid until pH=2. The crude product precipitate was collected by filtration and was re dissolved in acetonitrile (50 mL) and methylene chloride (15 mL) and allowed to precipitate slowly over a week. The resulting brown powder was collected by filtration and recrystallized from 10:3 acetic acid:water. The product (0.8 g, 3%) was isolated by filtration. Found: C, 65.55, H, 7.69%; C16H22O5 requires C, 65.29; H, 7.53% 1H NMR (d6-DMSO): δ 12.0, s, 1H (COOH); δ 11.4, s, 1H (aryl-hydroxyl); δ 9.2, s, 1H (aryl-hydroxyl); δ 7.2 d, 1H (aryl H); δ 7.0, dd, 1H, (arylH); δ 6.8, d, 1H (aryl H's), 3.0, t, 2H(CH2 α to carbonyl); δ 2.2, t, 2H (CH2 β to COOH); δ 1.6, multiplet, 2H (CH2 β to carbonyl), δ 1.5, multiplet, 2H (CH2 β to COOH), δ 1.3, multiplet, 8H (rest of CH2's). To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere Carbon disulfide was decanted away ice was carefully added until most of mixture was dissolved The insoluble material was collected by suction filtration washed with 2×100 mL of water The solid was then dissolved in 50 mL of 1 M aqueous sodium hydroxide stirred for 1 hour The crude product precipitate was collected by filtration was re dissolved in acetonitrile (50 mL) to precipitate slowly over a week The resulting brown powder was collected by filtration recrystallized from 10:3 acetic acid

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

Procedure: To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere, was added the previously made Oxacycloundecane-2,11-dione (37.95 g, 206 mmol), 1,4-diacetoxy-benzene (20 g, 103 mmol), and 200 mL carbon disulfide. Aluminum (III) trichloride (68.7 g, 515 mmol) was added and the reaction stirred for 72 hours. Carbon disulfide was decanted away, and ice was carefully added until most of mixture was dissolved. The insoluble material was collected by suction filtration and washed with 2×100 mL of water. The solid was then dissolved in 50 mL of 1 M aqueous sodium hydroxide and stirred for 1 hour. The solution was acidified with 1 M aqueous hydrochloric acid until pH=2. The crude product precipitate was collected by filtration and was re dissolved in acetonitrile (50 mL) and methylene chloride (15 mL) and allowed to precipitate slowly over a week. The resulting brown powder was collected by filtration and recrystallized from 10:3 acetic acid:water. The product (0.8 g, 3%) was isolated by filtration. Found: C, 65.55, H, 7.69%; C16H22O5 requires C, 65.29; H, 7.53% 1H NMR (d6-DMSO): δ 12.0, s, 1H (COOH); δ 11.4, s, 1H (aryl-hydroxyl); δ 9.2, s, 1H (aryl-hydroxyl); δ 7.2 d, 1H (aryl H); δ 7.0, dd, 1H, (arylH); δ 6.8, d, 1H (aryl H's), 3.0, t, 2H(CH2 α to carbonyl); δ 2.2, t, 2H (CH2 β to COOH); δ 1.6, multiplet, 2H (CH2 β to carbonyl), δ 1.5, multiplet, 2H (CH2 β to COOH), δ 1.3, multiplet, 8H (rest of CH2's). To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere Carbon disulfide was decanted away ice was carefully added until most of mixture was dissolved The insoluble material was collected by suction filtration washed with 2×100 mL of water The solid was then dissolved in 50 mL of 1 M aqueous sodium hydroxide stirred for 1 hour The crude product precipitate was collected by filtration was re dissolved in acetonitrile (50 mL) to precipitate slowly over a week The resulting brown powder was collected by filtration recrystallized from 10:3 acetic acid

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

Procedure: To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere, was added the previously made Oxacycloundecane-2,11-dione (20 g, 108.5 mmol), phenol (10.22 g, 108.5 mmol), and 200 mL carbon disulfide. Aluminum (III) trichloride (72.34 g, 542 mmol) was added and the reaction stirred for 72 hours. Carbon disulfide was decanted away, and ice was carefully added until most of mixture was dissolved. The insoluble material was collect by suction filtration and washed with 2×100 mL of water. The solid was then dissolved in 100 mL of 1 M aqueous sodium hydroxide and then carefully acidified with 1 M aqueous hydrochloric acid until pH=7.5 The solids that formed were removed by filtration and the parent solution was continued to be acidified until pH 2.5. The crude product precipitate was collected by filtration and was washed with 1×100 mL water. The crude product was dissolved in 100 mL of 1 M aqueous sodium hydroxide and then carefully acidified with 1 M aqueous hydrochloric acid until pH=7.5 and the impurities that precipitated were filtered off. The parent solution was further acidified until pH 2. The crude product was collected by filtration and washed with 2×50 mL water. The product was recrystallized form acetone. The isolated product (1.2 g, 4%) was collected by filtration. Found: C, 69.00; H, 7.81%; C16H22O4 requires C, 69.04; H, 7.97% 1H NMR (d6-DMSO): δ 12.0, bs, 1H(COOH); δ 10.3, bs, 1H (aryl-hydroxyl); δ 7.8 d, 2H (aryl H's); δ 6.8, d, 2H, (aryl H's); δ 2.9, t, 2H(CH2 α to carbonyl); δ 2.2, t, 2H (CH2 α to COOH); δ 1.5, multiplet, 4H(CH2's β to carbonyl & β to COOH), δ 1.3, multiplet, 8H (rest of CH2's). To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere Carbon disulfide was decanted away ice was carefully added until most of mixture was dissolved The insoluble material was collect by suction filtration washed with 2×100 mL of water The solid was then dissolved in 100 mL of 1 M aqueous sodium hydroxide that formed were removed by filtration The crude product precipitate was collected by filtration was washed with 1×100 mL water The crude product was dissolved in 100 mL of 1 M aqueous sodium hydroxide the impurities that precipitated were filtered off The crude product was collected by filtration washed with 2×50 mL water The product was recrystallized form acetone The isolated product (1.2 g, 4%) was collected by filtration

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

Procedure: To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere, was added the previously made Oxacycloundecane-2,11-dione (20 g, 108.5 mmol), phenol (10.22 g, 108.5 mmol), and 200 mL carbon disulfide. Aluminum (III) trichloride (72.34 g, 542 mmol) was added and the reaction stirred for 72 hours. Carbon disulfide was decanted away, and ice was carefully added until most of mixture was dissolved. The insoluble material was collect by suction filtration and washed with 2×100 mL of water. The solid was then dissolved in 100 mL of 1 M aqueous sodium hydroxide and then carefully acidified with 1 M aqueous hydrochloric acid until pH=7.5 The solids that formed were removed by filtration and the parent solution was continued to be acidified until pH 2.5. The crude product precipitate was collected by filtration and was washed with 1×100 mL water. The crude product was dissolved in 100 mL of 1 M aqueous sodium hydroxide and then carefully acidified with 1 M aqueous hydrochloric acid until pH=7.5 and the impurities that precipitated were filtered off. The parent solution was further acidified until pH 2. The crude product was collected by filtration and washed with 2×50 mL water. The product was recrystallized form acetone. The isolated product (1.2 g, 4%) was collected by filtration. Found: C, 69.00; H, 7.81%; C16H22O4 requires C, 69.04; H, 7.97% 1H NMR (d6-DMSO): δ 12.0, bs, 1H(COOH); δ 10.3, bs, 1H (aryl-hydroxyl); δ 7.8 d, 2H (aryl H's); δ 6.8, d, 2H, (aryl H's); δ 2.9, t, 2H(CH2 α to carbonyl); δ 2.2, t, 2H (CH2 α to COOH); δ 1.5, multiplet, 4H(CH2's β to carbonyl & β to COOH), δ 1.3, multiplet, 8H (rest of CH2's). To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere Carbon disulfide was decanted away ice was carefully added until most of mixture was dissolved The insoluble material was collect by suction filtration washed with 2×100 mL of water The solid was then dissolved in 100 mL of 1 M aqueous sodium hydroxide that formed were removed by filtration The crude product precipitate was collected by filtration was washed with 1×100 mL water The crude product was dissolved in 100 mL of 1 M aqueous sodium hydroxide the impurities that precipitated were filtered off The crude product was collected by filtration washed with 2×50 mL water The product was recrystallized form acetone The isolated product (1.2 g, 4%) was collected by filtration

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

Procedure: To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere, was added the previously made Oxacycloundecane-2,11-dione (37.95 g, 206 mmol), 1,4-diacetoxy-benzene (20 g, 103 mmol), and 200 mL carbon disulfide. Aluminum (III) trichloride (68.7 g, 515 mmol) was added and the reaction stirred for 72 hours. Carbon disulfide was decanted away, and ice was carefully added until most of mixture was dissolved. The insoluble material was collected by suction filtration and washed with 2×100 mL of water. The solid was then dissolved in 50 mL of 1 M aqueous sodium hydroxide and stirred for 1 hour. The solution was acidified with 1 M aqueous hydrochloric acid until pH=2. The crude product precipitate was collected by filtration and was re dissolved in acetonitrile (50 mL) and methylene chloride (15 mL) and allowed to precipitate slowly over a week. The resulting brown powder was collected by filtration and recrystallized from 10:3 acetic acid:water. The product (0.8 g, 3%) was isolated by filtration. Found: C, 65.55; H, 7.69%; C16H22O5 requires C, 65.29; H, 7.53%; 1H NMR (d6-DMSO): δ 12.0, s, 1H (COOH); δ 11.4, s, 1H (aryl-hydroxyl); δ 9.2, s, 1H (aryl-hydroxyl); δ 7.2 d, 1H (aryl H); δ 7.0, dd, 1H, (aryl H); δ 6.8, d, 1H (aryl H's), 3.0, t, 2H (CH2 α to carbonyl); δ 2.2, t, 2H (CH2 α to COOH); δ 1.6, multiplet, 2H (CH2 β to carbonyl), δ 1.5, multiplet, 2H (CH2 β to COOH), δ 1.3, multiplet, 8H (rest of CH2's). To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere Carbon disulfide was decanted away ice was carefully added until most of mixture was dissolved The insoluble material was collected by suction filtration washed with 2×100 mL of water The solid was then dissolved in 50 mL of 1 M aqueous sodium hydroxide stirred for 1 hour The crude product precipitate was collected by filtration was re dissolved in acetonitrile (50 mL) to precipitate slowly over a week The resulting brown powder was collected by filtration recrystallized from 10:3 acetic acid

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

Procedure: To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere, was added Oxacycloundecane-2,11-dione (20 g, 108.5 mmol), phenol (10.22 g, 108.5 mmol), and 200 mL carbon disulfide. Aluminum (III) trichloride (72.34 g, 542 mmol) was added and the reaction was stirred for 72 hours. Carbon disulfide was decanted away, and ice was carefully added until most of mixture was dissolved. The insoluble material was collect by suction filtration and washed with 2×100 mL of water. The solid was then dissolved in 100 mL of 1 M aqueous sodium hydroxide and then carefully acidified with 1 M aqueous hydrochloric acid until pH=7.5 The solids that formed were removed by filtration and the parent solution was continued to be acidified until pH 2.5. The crude product precipitate was collected by filtration and was washed with 1×100 mL water. The crude product was dissolved in 100 mL of 1 M aqueous sodium hydroxide and then carefully acidified with 1 M aqueous hydrochloric acid until pH=7.5 and the impurities that precipitated were filtered off. The parent solution was further acidified until pH 2. The crude product was collected by filtration and washed with 2×50 mL water. The product was recrystallized form acetone. The isolated product (1.2 g, 4%) was collected by filtration. Found: C, 69.00; H, 7.81%; C16H22O4 requires C, 69.04; H, 7.97%; 1H NMR (d6-DMSO): δ 12.0, bs, 1H (COOH); δ 10.3, bs, 1H (aryl-hydroxyl); δ 7.8 d, 2H (aryl H's); δ 6.8, d, 2H, (aryl H's); δ 2.9, t, 2H (CH2 α to carbonyl); δ 2.2, t, 2H (CH2 α to COOH); δ 1.5, multiplet, 4H (CH2's β to carbonyl & β to COOH), δ 1.3, multiplet, 8H (rest of CH2's). To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere Carbon disulfide was decanted away ice was carefully added until most of mixture was dissolved The insoluble material was collect by suction filtration washed with 2×100 mL of water The solid was then dissolved in 100 mL of 1 M aqueous sodium hydroxide that formed were removed by filtration The crude product precipitate was collected by filtration was washed with 1×100 mL water The crude product was dissolved in 100 mL of 1 M aqueous sodium hydroxide the impurities that precipitated were filtered off The crude product was collected by filtration washed with 2×50 mL water The product was recrystallized form acetone The isolated product (1.2 g, 4%) was collected by filtration

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

Procedure: Methylene chloride (10 ml), triethylamine (190 μl, 1.37 mmol) and sebacic anhydride (292.4 mg, 1.59 mmol) were added to (1S,2S)-2-amino-3-morpholino-1-phenyl-1-propanol (316.2 mg, 1.34 mmol), followed by stirring for 5 hours. Then, the solvent was evaporated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (chloroform:methanol=20:1 and chloroform:methanol=9:1) to obtain the title compound (171.1 mg, yield 30.4%) as colorless oil. Then, the solvent was evaporated under reduced pressure The resulting crude product was purified by silica gel column chromatography (chloroform:methanol=20:1 and chloroform:methanol=9:1)

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

Procedure: BTCA was reacted with two equivalents of methoxy PEG amine in refluxing THF for 5 hours to yield dimethoxy-PEG tetracarboxybenzoate, with two remaining carboxylic groups. The PEG-dimer was reacted with acetic anhydride and then with sebacic anhydride to form the tetra-armed diblock PEG2 -benzene-PSA2. to yield dimethoxy-PEG tetracarboxybenzoate

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

Procedure: BTCA was reacted with two equivalents of methoxy PEG amine in refluxing THF for 5 hours to yield dimethoxy-PEG tetracarboxybenzoate, with two remaining carboxylic groups. The PEG-dimer was reacted with acetic anhydride and then with sebacic anhydride to form the tetra-armed diblock PEG2 -benzene-PSA2. to yield dimethoxy-PEG tetracarboxybenzoate

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

Procedure: To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere, was added the previously made Oxacycloundecane-2,11-dione (37.95 g, 206 mmol), 1,4-diacetoxy-benzene (20 g, 103 mmol), and 200 mL carbon disulfide. Aluminum (III) trichloride (68.7 g, 515 mmol) was added and the reaction stirred for 72 hours. Carbon disulfide was decanted away, and ice was carefully added until most of mixture was dissolved. The insoluble material was collected by suction filtration and washed with 2×100 mL of water. The solid was then dissolved in 50 mL of 1 M aqueous sodium hydroxide and stirred for 1 hour. The solution was acidified with 1 M aqueous hydrochloric acid until pH=2. The crude product precipitate was collected by filtration and was re dissolved in acetonitrile (50 mL) and methylene chloride (15 mL) and allowed to precipitate slowly over a week. The resulting brown powder was collected by filtration and recrystallized from 10:3 acetic acid:water. The product (0.8 g, 3%) was isolated by filtration. Found: C, 65.55, H, 7.69%; C16H22O5 requires C, 65.29; H, 7.53% 1H NMR (d6-DMSO): δ 12.0, s, 1H (COOH); δ 11.4, s, 1H (aryl-hydroxyl); δ 9.2, s, 1H (aryl-hydroxyl); δ 7.2 d, 1H (aryl H); δ 7.0, dd, 1H, (arylH); δ 6.8, d, 1H (aryl H's), 3.0, t, 2H(CH2 α to carbonyl); δ 2.2, t, 2H (CH2 β to COOH); δ 1.6, multiplet, 2H (CH2 β to carbonyl), δ 1.5, multiplet, 2H (CH2 β to COOH), δ 1.3, multiplet, 8H (rest of CH2's). To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere Carbon disulfide was decanted away ice was carefully added until most of mixture was dissolved The insoluble material was collected by suction filtration washed with 2×100 mL of water The solid was then dissolved in 50 mL of 1 M aqueous sodium hydroxide stirred for 1 hour The crude product precipitate was collected by filtration was re dissolved in acetonitrile (50 mL) to precipitate slowly over a week The resulting brown powder was collected by filtration recrystallized from 10:3 acetic acid

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

Procedure: To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere, was added the previously made Oxacycloundecane-2,11-dione (20 g, 108.5 mmol), phenol (10.22 g, 108.5 mmol), and 200 mL carbon disulfide. Aluminum (III) trichloride (72.34 g, 542 mmol) was added and the reaction stirred for 72 hours. Carbon disulfide was decanted away, and ice was carefully added until most of mixture was dissolved. The insoluble material was collect by suction filtration and washed with 2×100 mL of water. The solid was then dissolved in 100 mL of 1 M aqueous sodium hydroxide and then carefully acidified with 1 M aqueous hydrochloric acid until pH=7.5 The solids that formed were removed by filtration and the parent solution was continued to be acidified until pH 2.5. The crude product precipitate was collected by filtration and was washed with 1×100 mL water. The crude product was dissolved in 100 mL of 1 M aqueous sodium hydroxide and then carefully acidified with 1 M aqueous hydrochloric acid until pH=7.5 and the impurities that precipitated were filtered off. The parent solution was further acidified until pH 2. The crude product was collected by filtration and washed with 2×50 mL water. The product was recrystallized form acetone. The isolated product (1.2 g, 4%) was collected by filtration. Found: C, 69.00; H, 7.81%; C16H22O4 requires C, 69.04; H, 7.97% 1H NMR (d6-DMSO): δ 12.0, bs, 1H(COOH); δ 10.3, bs, 1H (aryl-hydroxyl); δ 7.8 d, 2H (aryl H's); δ 6.8, d, 2H, (aryl H's); δ 2.9, t, 2H(CH2 α to carbonyl); δ 2.2, t, 2H (CH2 α to COOH); δ 1.5, multiplet, 4H(CH2's β to carbonyl & β to COOH), δ 1.3, multiplet, 8H (rest of CH2's). To a 500 mL flask, equipped with mechanical stirrer and under inert atmosphere Carbon disulfide was decanted away ice was carefully added until most of mixture was dissolved The insoluble material was collect by suction filtration washed with 2×100 mL of water The solid was then dissolved in 100 mL of 1 M aqueous sodium hydroxide that formed were removed by filtration The crude product precipitate was collected by filtration was washed with 1×100 mL water The crude product was dissolved in 100 mL of 1 M aqueous sodium hydroxide the impurities that precipitated were filtered off The crude product was collected by filtration washed with 2×50 mL water The product was recrystallized form acetone The isolated product (1.2 g, 4%) was collected by filtration