Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH:5]1[O:10][CH:9]([CH2:11][OH:12])[CH:8]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:7]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]1[O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[C:37]([NH:44][C@H:45]([C:49](O)=[O:50])[CH:46]([CH3:48])[CH3:47])([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>O1CCCC1>[C:40]([O:39][C:37](=[O:38])[NH:44][CH:45]([C:49](=[O:50])[NH:1][CH2:2][CH2:3][CH2:4][CH:5]1[CH:6]([O:29][CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:7]([O:21][CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:8]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:9]([CH2:11][OH:12])[O:10]1)[CH:46]([CH3:47])[CH3:48])([CH3:41])([CH3:43])[CH3:42]
Reactant: NCCCC1OC(CO)C(OCc2ccccc2)C(OCc2ccccc2)C1OCc1ccccc1
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)C(NC(=O)OC(C)(C)C)C(=O)NCCCC1OC(CO)C(OCc2ccccc2)C(OCc2ccccc2)C1OCc1ccccc1

Procedure:
[6-(3-Amino-propyl)-3,4,5-tris-benzyloxy-tetrahydro-pyran-2-yl]-methanol (from Example 12) (3.8 g, 6.3 mmol) was reacted with Boc-valine (1.37 g, 6.3 mmol) activated with BOP reagent (2.8 g, 6.3 mmol) and diisopropylethylamine (1.7 ml, 10 mmol) in tetrahydrofuran (10 ml). After 2 hours the solvent was removed under reduced pressure and ethyl acetate (100 ml) added to the oily residue which was subsequently washed with 1M hydrochloric acid (2×100 ml), saturated sodium bicarbonate (2×100 ml) and brine (100 ml), dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was purified on a rapid vacuum silica gel (0.040-0.063 mm; 100 g) column (70×200 mm) eluted with light petroleum (200 ml), 25% ethyl acetate in light petroleum (200 ml), 50% ethyl acetate in light petroleum (2×200 ml), 75% ethyl acetate in light petroleum (2×200 ml), and 100% ethyl acetate (2×100 ml) to give {2-methyl-1-[3-(3,4,5-tris-benzyloxy-6-hydroxymethyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]-propyl}-carbamic acid tert-butyl ester (tlc silica gel, Rf 0.13 in 50% EtOAc/Light Petroleum, ESMS (+ve) 713 (M+Na)) as an oil (2.4 g, 54%). This compound (1.2 g, 1.7 mmol) was reacted with a 1:1 mixture of trifluoroacetic acid and dichloromethane (10 ml) for 1 hour to remove the Boc protecting group. The reaction mixture was evaporated to dryness, diluted with dichloromethane (20 ml) and evaporated to remove all traces of trifluoroacetic acid. The crude product was reacted with Boc-aspartic acid, gamma-benzyl ester (581 mg, 1.8 mmol) activated with BOP reagent (79 6mg, 1.8 mmol) and diisopropylamine (0.869 ml, 5 mmol) in tetrahydrofuran (20 ml). After 2 hours the solvent was removed under reduced pressure and ethyl acetate (100 ml) added to the oily residue which was subsequently washed with 1M hydrochloric acid (2×100 ml), saturated sodium bicarbonate (2×100 ml) and brine (100 ml), dried over anhydrous sodium sulfate, and evaporated to dryness to give 3-tert-butoxycarbonylamino-N-{2-methyl-1-[3-(3,4,5-tris-benzyloxy-6-hydroxymethyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]-propyl}-succinamic acid benzyl ester, ESMS (+ve) 896 (M+H). This compound (approx. 1.7 mmol) was reacted with a 1:1 mixture of trifluoroacetic acid and dichloromethane (10 ml) for 1 hour to remove the Boc protecting group. The reaction mixture was evaporated to dryness, diluted with dichloromethane (20 ml) and evaporated to remove all traces of trifluoroacetic acid. The crude product was reacted with Boc-leucine (448 mg, 1.8 mmol) activated with BOP reagent (796 mg, 1.8 mmol) and diisopropylamine (0.869 ml, 5 mmol) in tetrahydrofuran (20 ml). After 2 hours the solvent was removed under reduced pressure and ethyl acetate (100 ml) added to the oily residue which was subsequently washed with 1M hydrochloric acid (2×100 ml), saturated sodium bicarbonate (2×100 ml) and brine (100 ml), dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was purified on a rapid vacuum silica gel (0.040-0.063 mm; 100 g) column (70×200 mm) eluted with light petroleum (200 ml), 25% ethyl acetate in light petroleum (200 ml), 50% ethyl acetate in light petroleum (2×200 ml), 75% ethyl acetate in light petroleum (2×200 ml), and 100% ethyl acetate (2×100 ml) to give 3-(2-tert-butoxycarbonylamino-4-methyl-pentanoylamino)-N-{2-methyl-1-[3-(3,4,5-tris-benzyloxy-6-hydroxymethyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]-propyl}-succinamic acid benzyl ester (tlc silica gel, Rf 0.42 in EtOAc, ESMS (+ve) 1009 (M+H), 1031 (M+Na)) as a white solid (850 mg, 48% combined for 2 deprotection and coupling steps). This compound (850 mg, 0.84 mmol) was dissolved in dry dichloromethane (10 ml) and triethylamine (0.557 ml, 4 mmol) and the mixture cooled to 0° C. whereupon phosphorous oxychloride (0.102 ml, 1.1 mmol) was added dropwise with stirring under an atmosphere of nitrogen. The mixture was allowed to warm to room temperature and stirred for 2 hours. The solvent was evaporated and the residue diluted with ether and centrifuged to remove insoluble salts. The supernatant was then evaporated and redissolved in a 1:1 mixture of acetone and water (20 ml) and kept at 45-50° C. for 2 hours. The solvent was removed under reduced pressure to give 3-(2-tert-butoxycarbonylamino-4-methyl-pentanoylamino)-N-{2-methyl-1-[3-(3,4,5-tris-benzyloxy-6-phosphonooxymethyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]-propyl}-succinamic acid benzyl ester, ESMS (−ve) 1088 (M−H). This compound was dissolved with 1% formic acid in a 1:1 mixture of tetrahydrofuran and water (100 ml), 10% palladium on carbon (100 mg) added and hydrogenated at 40 psi overnight. The mixture was filtered through celite and the filtrate evaporated to dryness to give 3-(2-tert-butoxycarbonylamino-4-methyl-pentanoylamino)-N-{2-methyl-1-[3-(3,4,5-trihydroxy-6-phosphonooxymethyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]-propyl}-succinamic acid, ESMS (−ve) 728 (M−H). From this was prepared the mono sodium salt by dissolving this compound in a 1:1 solution of water and ethanol (2 ml) and dropwise addition of this solution to sodium acetate (270 mg, 3.3 mmol) dissolved in ethanol (50 ml). The resulting solution was evaporated to dryness to give 3-(2-tert-butoxycarbonylamino-4-methyl-pentanoylamino)-N-{2-methyl-1-[3-(3,4,5-trihydroxy-6-phosphonooxymethyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]-propyl}-succinamic acid, monosodium salt as a white solid (490 mg, 80%). 1Hnmr (500 MHz, D2O): δ 0.73-0.84 (m, 12H), 1.28 (s, 9H), 1.35-1.70 (m, 7H), 1.97 (m, 1H), 2.45 2.69 (m, 2H), 3.00-3.19 (m, 2H), 3.45-3.98 (m, 9H), 4.53 (m, 1H).