(6z,9z,28z,31z)-Heptatriaconta-6,9,28,31-tetraen-19-ol

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

Procedure: The dilinoleyl methanol 6 (144 g, 272 mmol) was dissolved in 1 L of dichloromethane and to it the hydrochloride salt of dimethylaminobutyric acid 7 (55 g, 328 mmol) was added followed by diisopropylethylamine (70 mL) and DMAP (4 g). After stirring for 5 min. at ambient temperature, MC1 (80 g, 417 mmol) was added and the reaction mixture was stirred at room temperature overnight after which the TLC (silica gel, 5% MeOH in CH2Cl2) analysis showed complete disappearance of the starting alcohol. The reaction mixture was diluted with CH2Cl2 (500 mL) and washed with saturated NaHCO3 (400 mL), water (400 mL) and brine (500 mL). The combined organic layers were dried over anhyd. Na2SO4 and solvents were removed in vacuo. The crude product (180 g) thus obtained was purified by Flash column chromatography [2.5 Kg silica gel, Using the following eluents i) column packed with 6 L of 0.1% NEt3 in DCM; after loading ii) 4 L of 0.1% NEt3 in DCM; iii) 16 L of 2% MeOH—98% of 0.1% NEt3 in DCM; iv) 4 L of 2.5% MeOH—97.5% of 0.1% NEt3 in DCM; v) 12 L of 3% MeOH—97% of 0.1% NEt3 in DCM] to isolate the pure product 8 (MC3, 159 g, 91%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 5.46-5.23 (m, 8H), 4.93-4.77 (m, 1H), 2.83-2.66 (m, 4H), 2.37-2.22 (m, 4H), 2.20 (s, 6H), 2.10-1.96 (m, 9H), 1.85-1.69 (m, 2H), 1.49 (d, J=5.4, 4H), 1.39-1.15 (m, 39H), 0.95-0.75 (m, 6H). 13C NMR (101 MHz, CDCl3): δ 173.56, 130.38, 130.33, 128.17, 128.14, 7754, 77.22, 76.90, 74.44, 59.17, 45.64, 34.36, 32.69, 31.73, 29.87, 29.76, 29.74, 29.70, 29.56, 29.50, 27.44, 27.41, 25.84, 25.55, 23.38, 22.78, 14.27. EI-MS (+ve): MW calc. for C43H79NO2 (M+H)+: 642.6. found: 642.6. was added MC1 (80 g, 417 mmol) was added washed with saturated NaHCO3 (400 mL), water (400 mL) and brine (500 mL) The combined organic layers were dried over anhyd Na2SO4 and solvents were removed in vacuo The crude product (180 g) thus obtained was purified by Flash column chromatography [2.5 Kg silica gel

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

Procedure: To a mixture of dilinoleyl methanol (2.0 g, 3.8 mmol) and anhydrous sodium carbonate (0.2 g) in 100 mL of CH2Cl2 was added pydimium chlorochromate (PCC, 2.0 g, 9.5 mmol). The resulting suspension was stirred at room temperature for 60 min. Ether (300 mL) was then added into the mixture, and the resulting brown suspension was filtered through a pad of silica gel (300 mL). The silica gel pad was further washed with ether (3×200 mL). The ether filtrate and washes were combined. Evaporation of the solvent gave 3.0 g of an oily residual as a crude product. The crude product was purified by column chromatography on silica gel (230-400 mesh, 250 mL) eluted with 0-3% ether in hexanes. This gave 1.8 g (90%) of dilinoleyl ketone (V). 1H NMR (400 MHz, CDCl3) δ: 5.25-5.45 (8H, m, 4×CH═CH), 2.78 (4H, t, 2×C═C—CH2—C═C), 2.39 (4H, t, 2×COCH2), 2.05 (8H, q, 4× allylic CH2), 1.45-1.7 (4H, m), 1.2-1.45 (32H, m), 0.90 (6H, t, 2×CH3) ppm. the resulting brown suspension was filtered through a pad of silica gel (300 mL) The silica gel pad was further washed with ether (3×200 mL) Evaporation of the solvent

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

Procedure: To a mixture of dilinoleyl methanol (2.0 g, 3.8 mmol) and anhydrous sodium carbonate (0.2 g) in 100 mL of CH2Cl2 was added pydimium chlorochromate (PCC, 2.0 g, 9.5 mmol). The resulting suspension was stirred at room temperature for 60 min. Ether (300 mL) was then added into the mixture, and the resulting brown suspension was filtered through a pad of silica gel (300 mL). The silica gel pad was further washed with ether (3×200 mL). The ether filtrate and washes were combined. Evaporation of the solvent gave 3.0 g of an oily residual as a crude product. The crude product was purified by column chromatography on silica gel (230-400 mesh, 250 mL) eluted with 0-3% ether in hexanes. This gave 1.8 g (90%) of dilinoleyl ketone (V). 1H NMR (400 MHz, CDCl3) δ: 5.25-5.45 (8H, m, 4×CH═CH), 2.78 (4H, t, 2×C═C—CH2—C═C), 2.39 (4H, t, 2×COCH2), 2.05 (8H, q, 4× allylic CH2), 1.45-1.7 (4H, m), 1.2-1.45 (32H, m), 0.90 (6H, t, 2×CH3) ppm. the resulting brown suspension was filtered through a pad of silica gel (300 mL) The silica gel pad was further washed with ether (3×200 mL) Evaporation of the solvent

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

Procedure: To a mixture of dilinoleyl methanol (4.0 g, 7.2 mmol) and anhydrous potassium carbonate (0.4 g) in 100 mL of CH2Cl2 was added pyridinium chlorochromate (PCC, 4.0 g, 19 mmol). The resulting suspension was stirred at room temperature for 2 hours. Ether (300 mL) was then added into the mixture, and the resulting brown suspension was filtered through a pad of silica gel (150 mL). The silica gel pad was further washed with ether (3×75 mL). The ether filtrate and washes were combined. Evaporation of the solvent gave 5.1 g of an oily residual as a crude product. The crude product was purified by column chromatography on silica gel (230-400 mesh, 200 mL) eluted with 0-4% ethyl acetate in hexanes. This afforded 3.0 g (79%) of dilinoleyl ketone (V). the resulting brown suspension was filtered through a pad of silica gel (150 mL) The silica gel pad was further washed with ether (3×75 mL) Evaporation of the solvent

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

Procedure: To a mixture of dilinoleyl methanol (4.0 g, 7.2 mmol) and anhydrous potassium carbonate (0.4 g) in 100 mL of CH2Cl2 was added pyridinium chlorochromate (PCC, 4.0 g, 19 mmol). The resulting suspension was stirred at room temperature for 2 hours. Ether (300 mL) was then added into the mixture, and the resulting brown suspension was filtered through a pad of silica gel (150 mL). The silica gel pad was further washed with ether (3×75 mL). The ether filtrate and washes were combined. Evaporation of the solvent gave 5.1 g of an oily residual as a crude product. The crude product was purified by column chromatography on silica gel (230-400 mesh, 200 mL) eluted with 0-4% ethyl acetate in hexanes. This afforded 3.0 g (79%) of dilinoleyl ketone (V). the resulting brown suspension was filtered through a pad of silica gel (150 mL) The silica gel pad was further washed with ether (3×75 mL) Evaporation of the solvent

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

Procedure: To a mixture of dilinoleyl methanol (4.0 g, 7.2 mmol) and anhydrous potassium carbonate (0.4 g) in 100 mL of CH2Cl2 was added pyridinium chlorochromate (PCC, 4.0 g, 19 mmol). The resulting suspension was stirred at room temperature for 2 hours. Ether (300 mL) was then added into the mixture, and the resulting brown suspension was filtered through a pad of silica gel (150 mL). The silica gel pad was further washed with ether (3×75 mL). The ether filtrate and washes were combined. Evaporation of the solvent gave 5.1 g of an oily residual as a crude product. The crude product was purified by column chromatography on silica gel (230-400 mesh, 200 mL) eluted with 0-4% ethyl acetate in hexanes. This afforded 3.0 g (79%) of dilinoleyl ketone (V). the resulting brown suspension was filtered through a pad of silica gel (150 mL) The silica gel pad was further washed with ether (3×75 mL) Evaporation of the solvent

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

Procedure: A solution of trichloromethyl chloroformate (340 μL, 2.8 mmol) in anhydrous Et2O (5 mL) was cooled (−15° C.) and treated with a solution of dilinoleyl methanol (1.0 g, 1.9 mmol) and pyridine (230 μL, 2.8 mmol) in Et2O (5 mL). After stirring (1 h) the reaction mixture was filtered through a frit and the filtrate was added, dropwise, to a cool (0° C.) solution of 3-methylamino-propan-1-ol (1.1 mL, 11.3 mmol) in Et2O (5 mL). After stirring (5 min) the reaction mixture was filtered and concentrated. The crude material was subjected to chromatography (12%→20% EtOAc-hexanes) to yield (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl (3-hydroxypropyl)(methyl)carbamate (960 mg, 79%) as a colorless oil. Rf 0.17 (10% EtOAc-hexanes), FW 644.07, C42H77NO3. was filtered through a frit the filtrate was added After stirring (5 min) the reaction mixture was filtered concentrated

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

Procedure: To a solution of dilinoleyl methanol (1.0 g, 1.9 mmol) and pyridine (230 μL, 4.7 mmol) in anhydrous ether (10 mL) cooled to −15° C. under nitrogen was slowly added diphosgene (0.38 mL, 3.14 mmol). The reaction was stirred for 1 hour at −15° C., then N,N-dimethyl-N′-ethyl-ethylenediamine (2.2 mL, 14.2 mmol) was added. The solution was warmed to room temperature and stirred for 30 minutes. The solution was diluted with diethyl ether (50 mL) and filtered to remove the urea and ammonium salts. The ether filtrate was concentrated in vacuo to dryness and the residue was purified by column chromatography (100% ethyl acetate) to afford the title compound as a colorless oil (990 mg, 78%). 1H NMR (400 MHz, CDCl3): δ 5.41-5.27 (m, 8H), 4.77-4.69 (m, 1H), 3.55-3.20 (m, 4H), 2.79-2.72 (m, 4H), 2.72-2.56 (m, 1H), 2.55-2.21 (m, 7H), 2.08-1.96 (m, 8H), 1.58-1.44 (m, 4H), 1.39-1.15 (m, 36H), 1.10 (t, J=7.0 Hz, 3H), 0.90-0.82 (m, 6H). The solution was warmed to room temperature stirred for 30 minutes filtered to remove the urea and ammonium salts The ether filtrate was concentrated in vacuo to dryness the residue was purified by column chromatography (100% ethyl acetate)

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

Procedure: To a solution of dilinoleyl methanol (1.0 g, 1.9 mmol) and pyridine (230 μL, 4.7 mmol) in anhydrous ether (10 mL) cooled to −15° C. under nitrogen was slowly added diphosgene (380 μL, 3.1 mmol). The reaction was stirred for 20 minutes at −15° C., then N-hexyl-N′,N′-dimethylpropane-1,3-diamine (3.8 g, 20.3 mmol) was added as a solution in 4:1 ether/dichloromethane (10 mL). The solution was warmed to room temperature and stirring was continued for 20 minutes. Upon completion, the solution was diluted with diethyl ether (100 mL) and washed with saturated sodium bicarbonate (2×50 mL). The ether extract was dried on magnesium sulphate, filtered, concentrated in vacuo to dryness. The residue was purified by column chromatography (100% ethyl acetate) to afford the title compound as a colorless oil (1.1 g, 76%). 1H NMR (400 MHz, CDCl3): δ 5.43-5.26 (m, 8H), 4.80-4.68 (m, 1H), 3.35-3.15 (m, 4H), 2.81-2.75 (m, 4H), 2.66-2.25 (m, 8H), 2.10-1.70 (m, 14H), 1.64-1.46 (m, 6H), 1.40-1.20 (m, 38H), 1.00-0.93 (m, 3H), 0.92-0.86 (m, 6H). The solution was warmed to room temperature stirring was continued for 20 minutes washed with saturated sodium bicarbonate (2×50 mL) The ether extract was dried on magnesium sulphate filtered concentrated in vacuo to dryness The residue was purified by column chromatography (100% ethyl acetate)

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

Procedure: To a solution of dilinoleyl methanol (1.0 g, 1.9 mmol) and pyridine (230 μL, 4.7 mmol) in anhydrous ether (10 mL) cooled to −15° C. under nitrogen was slowly added diphosgene (380 μL, 3.1 mmol). The reaction was stirred for 20 minutes at −15° C., then N-hexyl-N′,N′-dimethylpropane-1,3-diamine (3.8 g, 20.3 mmol) was added as a solution in 4:1 ether/dichloromethane (10 mL). The solution was warmed to room temperature and stirring was continued for 20 minutes. Upon completion, the solution was diluted with diethyl ether (100 mL) and washed with saturated sodium bicarbonate (2×50 mL). The ether extract was dried on magnesium sulphate, filtered, concentrated in vacuo to dryness. The residue was purified by column chromatography (100% ethyl acetate) to afford the title compound as a colorless oil (1.1 g, 76%). 1H NMR (400 MHz, CDCl3): δ 5.43-5.26 (m, 8H), 4.80-4.68 (m, 1H), 3.35-3.15 (m, 4H), 2.81-2.75 (m, 4H), 2.66-2.25 (m, 8H), 2.10-1.70 (m, 14H), 1.64-1.46 (m, 6H), 1.40-1.20 (m, 38H), 1.00-0.93 (m, 3H), 0.92-0.86 (m, 6H). The solution was warmed to room temperature stirring was continued for 20 minutes washed with saturated sodium bicarbonate (2×50 mL) The ether extract was dried on magnesium sulphate filtered concentrated in vacuo to dryness The residue was purified by column chromatography (100% ethyl acetate)

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

Procedure: To a solution of dilinoleyl methanol (1.0 g, 1.9 mmol) and pyridine (230 μL, 4.7 mmol) in anhydrous ether (10 mL) cooled to −15° C. under nitrogen was slowly added diphosgene (0.38 mL, 3.14 mmol). The reaction was stirred for 1 hour at −15° C., then N,N-dimethyl-N′-ethyl-ethylenediamine (2.2 mL, 14.2 mmol) was added. The solution was warmed to room temperature and stirred for 30 minutes. The solution was diluted with diethyl ether (50 mL) and filtered to remove the urea and ammonium salts. The ether filtrate was concentrated in vacuo to dryness and the residue was purified by column chromatography (100% ethyl acetate) to afford the title compound as a colorless oil (990 mg, 78%). 1H NMR (400 MHz, CDCl3): δ 5.41-5.27 (m, 8H), 4.77-4.69 (m, 1H), 3.55-3.20 (m, 4H), 2.79-2.72 (m, 4H), 2.72-2.56 (m, 1H), 2.55-2.21 (m, 7H), 2.08-1.96 (m, 8H), 1.58-1.44 (m, 4H), 1.39-1.15 (m, 36H), 1.10 (t, J=7.0 Hz, 3H), 0.90-0.82 (m, 6H). The solution was warmed to room temperature stirred for 30 minutes filtered to remove the urea and ammonium salts The ether filtrate was concentrated in vacuo to dryness the residue was purified by column chromatography (100% ethyl acetate)

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

Procedure: To a solution of dilinoleylmethanol (II, 560 mg, 1 mmol) and dry triethylamine (0.44 g, 4.2 mmol) in 50 mL of anhydrous CH2Cl2 was added dropwise 3-bromopropionyl chloride (technical grade, 0.34 mL) under nitrogen. The resulting mixture was stirred at room temperature for 3 days. The organic phase was diluted with 50 mL of dichloromethane and washed with water (3×50 mL), brine (50 mL), and dried over anhydrous Na2SO4. The solvent was evaporated to afford 610 mg of brownish oil as a crude product. The crude product was purified by column chromatography on silica gel (230-400 mesh, 100 mL) with 0-3% ethyl acetate gradient in hexanes as eluent. This resulted in 540 g of a mixture of III as a major product and a by-product. The mixture was used in the following step without further purification. washed with water (3×50 mL), brine (50 mL) dried over anhydrous Na2SO4 The solvent was evaporated