Reaction SMILES: [CH2:1]([OH:16])[CH2:2][O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][OH:15].[H-].[Na+].[C:19]([NH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]Br)([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>O1CCCC1>[C:19]([NH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][O:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH2:8][CH2:7][O:6][CH2:5][CH2:4][O:3][CH2:2][CH2:1][OH:16])([O:21][CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)=[O:20]
Reactant: OCCOCCOCCOCCOCCO
Reactant: O=C(NCCCCCBr)OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(NCCCCCOCCOCCOCCOCCOCCO)OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 56.4 %

Procedure:
A solution of pentaethylene glycol (5.0 g) in 50 mL of tetrahydrofuran was added to a rapidly stirred suspension of NaH (0.42 g of 60%) in 40 mL of tetrahydrofuran. The reaction mixture was kept under nitrogen and suspended in an ice-water bath and stirred for 0.5 h. A solution of N-CBZ-5-amino-1-bromopentane (3.78 g) in 30 mL of tetrahydrofuran was added and the mixture stirred in the ice-water bath for 1 h, then at room temperature for 18 h. The solvent was removed in vacuo and the residue was purified on silica gel, eluting with a gradient of 2-propanol in chloroform. Fractions containing the product (TLC Rf 0.30, CHCl3/2-propanol 95:5) were combined and the solvent removed to give 3.25 g of N-CBZ-20-amino-3,6,9,12,15-penta-oxa-1-eicosanol as an oil. A solution of N-CBZ-20-amino-3,6,9,12,15-penta-oxa-1-eicosanol (3.25 g) in 50 mL of tetrahydrofuran was added to a rapidly stirred suspension of NaH (0.28 g of 60%) in 25 mL of tetrahydrofuran. The reaction mixture was kept under nitrogen and suspended in an ice-water bath and stirred for 0.5 h. To the solution was added tert-butyl 1-bromoacetate (1.15 mL) and the mixture stirred in the ice-water bath for 1 h, then at room temperature for four days. The solvent was removed in vacuo and the residue suspended in 100 mL of chloroform and washed with water (50 mL). The chloroform solution was dried over Na2SO4, filtered and the solvent removed in vacuo to give an oil. This oil was purified on silica gel, eluting with a gradient of 2-propanol in chloroform. Fractions containing the product (TLC Rf 0.45, CHCl3/2-propanol 95:5) were combined and the solvent removed to give 3.24 g of tert-butyl N-CBZ-23-amino-3,6,9,12,15,18-hexa-oxa-1-tricosanoate as a colorless oil. An aliquot of the tert-butyl N-CBZ-23-amino-3,6,9,12,15,18-hexa-oxa-1-tricosanoate (0.49 g) was dissolved in 10 mL of 4 N HCl in dioxane and stirred at room temperature for 3 h. The solvents were removed in vacuo. The resultant crude N-CBZ-23-amino-3,6,9,12,15,18-hexa-oxa-1-tricosanoic acid was dissolved in 15 mL of dimethylformamide. To this solution was added N-hydroxysuccinimide (0.10 g), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (0.16 g) and N4-(5′-aminopentyl)-N1,N9,N12-tris(tert-butyloxycarbonyl)spermine (0.50 g). The solution was stirred at room temperature for 2.5 days. The dimethylformamide was removed in vacuo and the residue taken up in chloroform (100 mL). The chloroform solution was washed sequentially with 0.1 N HCl (75 mL) and sat. NaHCO3. The chloroform solution was dried over Na2SO4, filtered and the solvent removed in vacuo to give an oil. This oil was purified on silica. gel, eluting with a gradient of 2-propanol in chloroform. Fractions containing the product (TLC Rf 0.33, CHCl3/methanol 9:1) were combined and the solvent removed to give 0.19 g of N4-(5-N-(N-CBZ-23′-amino-3′,6′,9′,12′-15′-18′-hexa-oxa-tricosanamido)aminopentyl)-N1,N9,N12-tris(tert-butyloxycarbonyl)spermine as a colorless oil. This oil was dissolved in 50 mL of ethyl acetate and treated with 0.19 g of 10% Pd/C and 50 PSIG H2 for 2.5 h at room temperature. The Pd/C was removed by filtration through diatomaceous earth and solvent removed from the filtrate in vacuo to give N4-(5-N-(23′-amino-3′,6′,9′,12′-15′-18′-hexa-oxa-tricosanamido)aminopentyl)-N1,N9,N12-tris(tert-butyloxycarbonyl)spermine as a colorless oil (0.13 g). N4-(5-N-(23′-amino-3′,6′,9′,12′-15′-18′-hexa-oxa-tricosanamido)aminopentyl)-N1,N9,N12-tris(tert-butyloxycarbonyl)spermine (0.13 g) was dissolved in tetrahydrofuran (20 mL) and to the solution was added 0.048 mL of diisopropylethylamine and 0.073 g of succinimidyl S-α-3′-propionyl tetra-O-acetyl-thiomannoside, and the solution stirred at room temperature for 20 h. The solvent was removed in vacuo to give a glass. This glass was purified on silica gel, eluting with a gradient of methanol in chloroform. Fractions containing the product (TLC Rf 0.36, CHCl3/methanol 9:1) were combined and the solvent removed to give 0.10 g of N4-(5-N-(23′-N-(S-α-3′-propionamido tetra-O-acetyl-thiomannoside)-3′,6′,9′,12′-15′-18′-hexa-oxa-triconsanamido)aminopentyl)-N1,N9,N12-tris (tert-butyloxycarbonyl)spermine as an oil. FAB mass spectra, MH+=3328. The N4-(5-N-(23′-N-(S-α-3′-propionamido tetra-O-acetyl-thiomannoside)-3′,6′,9′,12′-15′-18′-hexa-oxa-tricosanamido)aminopentyl)-N1,N9,N12-tris(tert-butyloxycarbonyl)spermine (0.55 g) was dissolved in 10 mL of trifluoroacetic acid and stirred at room temperature for 2 h. The solvent was removed in vacua and the residue dissolved in chloroform and the solvent removed (2×20 mL) to give 0.76 g of N4-(5-N-(23′-N-(S-α-3′-propionamido tetra-O-acetyl-thiomannoside)-3′,6′,9′,12′-15′-18′-hexa-oxa-tricosanamido)aminopentyl)-spermine as an oil. This oil was dissolved in 20 mL of methanol and to the solution was added 20 mL of water and 0.85 g of Na2CO3, and the solution stirred at room temperature for 6.5 h. The solvents were removed in vacua and the residue taken up in 6 mL of 1% acetic acid and purified in four 1.5 mL aliquots on three Sephadex™ G-25 medium columns (12 mL each), eluting with 1% acetic acid. Fractions containing the product were combined and lyophilized to give 0.22 g of N4-(5-N-(23′-N-(S-α-3′-propionamido thiomannoside)-3′,6′,9′,12′-15′-18′-hexa-oxa-tricosanamido)aminopentyl)-spermine tetraacetate as an oil.