(E,2S,3R)-2-aminooctadec-4-ene-1,3-diol

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

Procedure: In a procedure similar to Grode and Cardellina D-erythro-sphingosine (4, 2 mg, 6.7 μmol, Sigma) in acetic anhydride (1 ml) and pyridine (2 ml) was stirred at 25° C. for 4.5 h, at which time no starting material could be observed by TLC. The solvent was removed by a stream of nitrogen to give 133: white solid; silica TLC Rf 0.86 (3:12:2:2 CHCl3/1-BuOH/AcOH/H2O, phosphomolybdic acid), 0.65 (9:1 CHCl3/MeOH, phosphomolybdic acid); FABMS m/z 580, 426, 366, 306, 264; CIMS m/z 468, 454, 426, 424, 394, 366, 364, 306, 264, 144, 85, 84, 83, 61. The solvent was removed by a stream of nitrogen

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.) solution of 38.1 mg (0.127 mmol) of D-erythro-sphingosine 1 in 3.0 mL of dichloromethane was added 61.5 μL (0.762 mmol) of pyridine, 72.0 μL (0.762 mmol) of acetic anhydride and 0.78 mg (6.4 μmol) of 4-dimethylaminopyridine. The solution was warmed to 25° C., stirred for 2 h and poured in 30 mL of dichloromethane. The mixture was washed with 40 mL each of saturated aqueous sodium bicarbonate, saturated aqueous cupric sulfate, brine and dried over anhydrous sodium sulfate. Concentration in vacuo yielded 52.3 mg (97%) of nearly pure triacetate as an off-white solid. Recrystallization from hexanes afforded 48.2 mg (89%) of pure triacetate as feathery white crystals, mp 102-103° C. A second recrystallization from diethyl ether:hexanes gave an analytical sample as feathery white crystals, mp 103.0-103.5° C. The mixture was washed with 40 mL each of saturated aqueous sodium bicarbonate, saturated aqueous cupric sulfate, brine dried over anhydrous sodium sulfate Concentration in vacuo

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

Procedure: To a solution of D-erythro-sphingosine (46 mg, 0.153 mmol) in CH2Cl2 (1.5 mL) at room temperature, Et3N (32 μL, 0.230 mmol), TBDPSCl (44 μL, 0.169 mmol) and 4-DMAP (ca. 5 mg, cat.) were added. After stirring for 4 h, the reaction was quenched with H2O (10 mL), extracted with EtOAc (3×10 mL), dried over Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography on silica (hexane/EtOAc 5:1 to 100% EtOAc) to obtain 136 as a colorless oil (33 mg, 40% yield). the reaction was quenched with H2O (10 mL) extracted with EtOAc (3×10 mL) dried over Na2SO4 concentrated in vacuo The crude was purified by column chromatography on silica (hexane/EtOAc 5:1 to 100% EtOAc)

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

Procedure: To a solution of D-erythro-sphingosine (46 mg, 0.153 mmol) in CH2Cl2 (1.5 mL) at room temperature, Et3N (32 μL, 0.230 mmol), TBDPSCl (44 μL, 0.169 mmol) and 4-DMAP (ca. 5 mg, cat.) were added. After stirring for 4 h, the reaction was quenched with H2O (10 mL), extracted with EtOAc (3×10 mL), dried over Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography on silica (hexane/EtOAc 5:1 to 100% EtOAc) to obtain 136 as a colorless oil (33 mg, 40% yield). the reaction was quenched with H2O (10 mL) extracted with EtOAc (3×10 mL) dried over Na2SO4 concentrated in vacuo The crude was purified by column chromatography on silica (hexane/EtOAc 5:1 to 100% EtOAc)

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

Procedure: In a procedure similar to Grode and Cardellina,93 D-erythro-sphingosine (4, 2 mg, 6.7 μmol, Sigma) in acetic anhydride (1 mL) and pyridine (2 mL) was stirred at 25° C. for 4.5 h, at which time no starting material could be observed by TLC. The solvent was removed by a stream of nitrogen to give 133: white solid; silica TLC Rf 0.86 (3:12:2:2 CHCl3/1-BuOH/AcOH/H2O, phosphomolybdic acid), 0.65 (9:1 CHCI3/MeOH, phosphomolybidic acid); FABMS m/z 580, 426, 366, 306, 264; CIMS m/z 468, 454, 426, 424, 394, 366, 364, 306, 264, 144, 85, 84, 83, 61. The solvent was removed by a stream of nitrogen

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

Procedure: 5.0 gr of sphingosine (16.70) mM), prepared according to Example 4, are reacted with 2.1 gr of the sodium salt of fluoroacetic acid (20.88 mM), in the presence of 5.3 gr of 2-chloro-1-methylpyridine iodide (20.88 mM) and 5.8 cc of triethylamine (42.00 mM) in 80 cc of dimethylformamide, at room temperature overnight. The solvent is evaporated, and the residue is gathered in CH2Cl2 and washed with H2O. It is anhydrified and purified by chromatography, eluting with a mixture of CH2 Cl2 /ethyl acetate/CH3CH 70:30:1 v/v/v. The solvent is evaporated washed with H2O purified by chromatography eluting with a mixture of CH2 Cl2 /ethyl acetate/CH3CH 70:30:1 v/v/v

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

Procedure: 5.0 gr of sphingosine (16.70 mM), prepared according to Example 4, 2.1 gr of N-acetylglycine (18.37 mM) and 3.8 gr of dicyclohexylcarbodiimide (18.40 mM) are left to react in 150 cc of chloroform, under warm conditions overnight. The reaction mixture is placed in a freezer to precipitate. The urea is filtered, and the chloroform solution is washed with H2O. The raw material is purified by chromatography using a mixture of CH2Cl2 /ethyl acetate/CH3OH, 70:30:10 v/v/v. are left to precipitate The urea is filtered the chloroform solution is washed with H2O The raw material is purified by chromatography a mixture of CH2Cl2 /ethyl acetate/CH3OH, 70:30:10 v/v/v

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

Procedure: 5.0 gr of sphingosine (16.70 mM), prepared according to Example 4, 2.1 gr of N-acetylglycine (18.37 mM) and 3.8 gr of dicyclohexylcarbodiimide (18.40 mM) are left to react in 150 cc of chloroform, under warm conditions overnight. The reaction mixture is placed in a freezer to precipitate. The urea is filtered, and the chloroform solution is washed with H2O. The raw material is purified by chromatography using a mixture of CH2Cl2 /ethyl acetate/CH3OH, 70:30:10 v/v/v. are left to precipitate The urea is filtered the chloroform solution is washed with H2O The raw material is purified by chromatography a mixture of CH2Cl2 /ethyl acetate/CH3OH, 70:30:10 v/v/v

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

Procedure: To a solution of sphingosine (100 mg, 0.33 mmol) in CH2Cl2 (3 mL) was added EDCI (128 mg, 0.66 mmol) and DMAP (cat.). Under stirring, stearic acid (95 mg, 0.33 mmol in 10 mL CH2Cl2) was added dropwise over a period time of 16 h. The reaction was stirred under argon for 24 h at rt. Solvent was evaporated and the residue was applied to silica gel column chromatography (CHCl3:MeOH=9:1, Rf=0.43) to afford 8 as a white powder (140 mg, 75%). 1H NMR (600 MHz, CDCl3) δ 0.88 (t, J=6.8 Hz, 6H), 1.26-1.40 (m, 50H), 1.64 (t, J=7.2 Hz, 2H), 2.06 (dd, J=14.4, 7.2 Hz, 2H), 2.24 (t, J=7.2 Hz, 2H), 3.71 (m, 1H), 3.91-3.97 (m, 2H), 4.32 (m, 1H), 5.42 (dd, J=15.6, 6.6 Hz, 1H), 5.79 (dt, J=15.6, 6.6 Hz, 1H), 6.28 (d, J=7.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 14.3, 22.9, 26.0, 29.4, 29.5, 29.6, 29.7, 29.8, 29.9, 32.2, 32.6, 54.7, 62.8, 74.9, 129.0, 134.6, 174.2. ESIMS calc'd for C36H71NNaO3 [M+Na]+ 588.53. found: 588.18. The reaction was stirred under argon for 24 h at rt Solvent was evaporated

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

Procedure: 5.0 gr of sphingosine (16.70) mM), prepared according to Example 4, are reacted with 2.1 gr of the sodium salt of fluoroacetic acid (20.88 mM), in the presence of 5.3 gr of 2-chloro-1-methylpyridine iodide (20.88 mM) and 5.8 cc of triethylamine (42.00 mM) in 80 cc of dimethylformamide, at room temperature overnight. The solvent is evaporated, and the residue is gathered in CH2Cl2 and washed with H2O. It is anhydrified and purified by chromatography, eluting with a mixture of CH2Cl2 /ethyl acetate/CH3CH 70:30:1 v/v/v. The solvent is evaporated washed with H2O purified by chromatography eluting with a mixture of CH2Cl2 /ethyl acetate/CH3CH 70:30:1 v/v/v

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

Procedure: 5.0 gr of sphingosine (16.70 mM), prepared according to Example 4, 2.1 gr of N-acetylglycine (18.37 mM) and 3.8 gr of dicyclohexylcarbodiimide (18.40 mM) are left to react in 150 cc of chloroform, under warm conditions overnight. The reaction mixture is placed in a freezer to precipitate. The urea is filtered, and the chloroform solution is washed with H2O. The raw material is purified by chromatography using a mixture of CH2Cl2 /ethyl acetate/CH3OH, 70:30:10 v/v/v. are left to precipitate The urea is filtered the chloroform solution is washed with H2O The raw material is purified by chromatography a mixture of CH2Cl2 /ethyl acetate/CH3OH, 70:30:10 v/v/v

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

Procedure: In a procedure similar to Grode and Cardellina D-erythro-sphingosine (4, 2 mg, 6.7 μmol, Sigma) in acetic anhydride (1 ml) and pyridine (2 ml) was stirred at 25° C. for 4.5 h, at which time no starting material could be observed by TLC. The solvent was removed by a stream of nitrogen to give 133: white solid; silica TLC Rf 0.86 (3:12:2:2 CHCl3/1-BuOH/AcOH/H2O, phosphomolybdic acid), 0.65 (9:1 CHCl3/MeOH, phosphomolybdic acid); FABMS m/z 580, 426, 366, 306, 264; CIMS m/z 468, 454, 426, 424, 394, 366, 364, 306, 264, 144, 85, 84, 83, 61. The solvent was removed by a stream of nitrogen