Reaction SMILES: [CH2:1]([O:8][P:9]([C@@:19]1([O:57][C@H:56]([CH2:58][O:59][C@@H:60]2[O:110][C@H:109]([CH2:111][O:112][CH2:113][C:114]3[CH:119]=[CH:118][CH:117]=[CH:116][CH:115]=3)[C@@H:95]([O:96][P:97]3(=[O:108])[O:103][CH2:102][C:101]4[CH:104]=[CH:105][CH:106]=[CH:107][C:100]=4[CH2:99][O:98]3)[C@H:62]([O:63][C:64](=[O:94])[CH2:65][C@H:66]([O:78][C:79](=[O:93])[CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH2:89][CH2:90]CC)[CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75]CC)[C@H:61]2[NH:120][C:121](=[O:149])[CH2:122][C@H:123]([O:135][C:136](=[O:148])[CH2:137][CH2:138][CH2:139][CH2:140][CH2:141][CH2:142][CH2:143][CH2:144][CH2:145][CH2:146][CH3:147])[CH2:124][CH2:125][CH2:126][CH2:127][CH2:128][CH2:129][CH2:130][CH2:131][CH2:132][CH2:133][CH3:134])[C@@H:47]([O:48][CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C@H:22]([O:23][C:24](=[O:46])[CH2:25][C@H:26]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]CC)[C@H:21]1[NH:150][C:151](=[O:173])[CH2:152][C@H:153]([O:165][CH2:166][C:167]1[CH:172]=[CH:171][CH:170]=[CH:169][CH:168]=1)[CH2:154][CH2:155][CH2:156][CH2:157][CH2:158][CH2:159][CH2:160][CH2:161][CH2:162][CH2:163][CH3:164])[OH:20])([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CCCCCC.C(OCC)(=O)C>[CH2:1]([O:8][P:9]([C@@:19]1([O:57][C@H:56]([CH2:58][O:59][C@@H:60]2[O:110][C@H:109]([CH2:111][O:112][CH2:113][C:114]3[CH:119]=[CH:118][CH:117]=[CH:116][CH:115]=3)[C@@H:95]([O:96][P:97]3(=[O:108])[O:98][CH2:99][C:100]4[CH:107]=[CH:106][CH:105]=[CH:104][C:101]=4[CH2:102][O:103]3)[C@H:62]([O:63][C:64](=[O:94])[CH2:65][C@H:66]([O:78][C:79](=[O:93])[CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH2:89][CH3:90])[CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH3:75])[C@H:61]2[NH:120][C:121](=[O:149])[CH2:122][C@H:123]([O:135][C:136](=[O:148])[CH2:137][CH2:138][CH2:139][CH2:140][CH2:141][CH2:142][CH2:143][CH2:144][CH2:145][CH2:146][CH3:147])[CH2:124][CH2:125][CH2:126][CH2:127][CH2:128][CH2:129][CH2:130][CH2:131][CH2:132][CH2:133][CH3:134])[C@@H:47]([O:48][CH2:49][C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=2)[C@H:22]([O:23][C:24](=[O:46])[CH2:25][C@H:26]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[C@H:21]1[NH:150][C:151](=[O:173])[CH2:152][C@H:153]([O:165][CH2:166][C:167]1[CH:172]=[CH:171][CH:170]=[CH:169][CH:168]=1)[CH2:154][CH2:155][CH2:156][CH2:157][CH2:158][CH2:159][CH2:160][CH2:161][CH2:162][CH2:163][CH3:164])[OH:20])([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)O[C@@H]1[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@H](OC[C@H]2O[C@@](O)(P(=O)(OCc3ccccc3)OCc3ccccc3)[C@H](NC(=O)C[C@@H](CCCCCCCCCCC)OCc3ccccc3)[C@@H](OC(=O)C[C@@H](CCCCCCCCCCC)OCc3ccccc3)[C@@H]2OCc2ccccc2)O[C@H](COCc2ccccc2)[C@H]1OP1(=O)OCc2ccccc2CO1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)N[C@H]1[C@H](OC[C@H]2O[C@@](O)(P(=O)(OCc3ccccc3)OCc3ccccc3)[C@H](NC(=O)C[C@@H](CCCCCCCCCCC)OCc3ccccc3)[C@@H](OC(=O)C[C@@H](CCCCCCCCC)OCc3ccccc3)[C@@H]2OCc2ccccc2)O[C@H](COCc2ccccc2)[C@@H](OP2(=O)OCc3ccccc3CO2)[C@@H]1OC(=O)C[C@@H](CCCCCCCCC)OC(=O)CCCCCCCCCCC
Yield: 72 %

Procedure:
Compound 43 (16 mg, 0.72 μmol) was deprotected in a manner similar to the synthesis of 32 with HF/pyridine (50 μL) in THF (3 mL) to yield the intermediate lactol as a white solid (13 mg, 86%). Rf=0.35 (hexane/ethyl acetate, 1/1, v/v). 1H NMR (500 MHz, CDCl3): δ 7.40-7.18 (m, 24H, aromatic), 6.37 (d, 1H, JNH′,2′=7.5 Hz, NH′), 6.26 (d, 1H, JNH,2=9.5 Hz, NH), 5.55 (d, 1H, =8.0 Hz, H-1′), 5.52 (t, 1H, J2′,3′=J3′,4′=9.5 Hz, H-3′), 5.42 (t, 1H, J2,3=J3,4=10.0 Hz, H-3), 5.28-5.24 (m, 1H, H-3L), 5.15-4.96 (m, 6H, H-1, H-3L, C6H4(CH2O)2P), 4.65-4.43 (m, 9H, H-4′, 4×CH2Ph), 4.24-4.19 (m, 1H, H-2), 4.13-4.09 (m, 1H, H-5), 3.94-3.82 (m, 4H, H-6a, H-6′a, 2×H-3S), 3.77-3.68 (m, 3H, H-5′, H-6b, H-6′b), 3.37-3.31 (m, 2H, H-2′, H-4), 2.69-2.27 (m, 12H, 2×H-2L, 2×H-2S, 2×H-20, 1.59 (broad, 12H, 2×H-4L, 2×H-4S, 2×H-3L′), 1.26 (broad, 80H, 40×CH2, lipid), 0.91-0.88 (m, 18H, 6×CH3, lipid). HR MS (m/z) calculated for C124H195N2O22PSi[M+Na]+, 2118.3837; found, 2118.6284. The anomeric hydroxyl of the resulting lactol (16.0 mg, 0.0073 mmol) was phosphorylated in a manner similar to the synthesis of 34 to afford 45 as a white solid (11.0 mg, 72%).