Reaction Steps
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%).
