ACCEPTED MANUSCRIPT
13C NMR: 177.8, 177.7, 177.2, 176.8, 85.4, 71.5, 71.2, 69.8, 67.0, 61.2, 39.0, 38.7, 38.6, 38.6,
27.1, 27.0; HRMS (ESI): m/z calcd for C26H46NO9 [M+H]+: 516.3173, found: 516.3181.
4.3. D-24-2’,3’,4’,6’-Tetra-O-pivaloyl-β-D-galactopyranosyl-amino-24-cyano-3-hydroxy-
5β-cholane (8)
A solution of 7 (543 mg, 1.05 mmol) and lithocholic aldehyde 3 (500 mg, 1.05 mmol) was
stirred in n-pentane (60 mL) in the presence of 4 Å molecular sieves (1 g) at room
temperature for 20 h. The molecular sieves were filtered off, and the solvent was evaporated
in vacuo. The crude aldimine 7 was used in the next step without further purification.
To a solution of trimethylsilyl cyanide (0.22 mL, 1.76 mmol) and SnCl4 (0.22 mL, 1.76
mmol) in THF (20 mL) at -40 °C, a solution of the imine 7 (1.043 g, 1.22 mmol) in THF (10
mL) was added within 5 min. The mixture was then stirred at -18 °C for 3 h. The reaction was
monitored by TLC, when completed, the mixture was washed with 1 M HCI, saturated
aqueous NaHCO3, and water, dried over NaSO4, and concentrated in vacuo. The crude
product was separated by column chromatography (hexane - ethyl acetate v/v 8.5 : 1.5) and
549 mg (51%, a mixture 24R/24S 3:1) of a white solid was isolated. During chromatography a
partial separation of isomers was obtained and more polar 24R-stereoisomer was isolated in
pure form. Data for 24R product: Mp 104-106 °C; IR (ATR, cm-1) ν: 3603, 3361, 2974, 1732,
1480, 1280, 1150, 1031; 1H NMR (400 MHz, CDCl3): δ 5.44 (1H, d, J = 3.2 Hz), 5.18 (1H,
dd, J = 10.3, 3.2 Hz), 5.03 (1H, dd, J = 10.3, 8.9 Hz), 4.19 (1H, dd, J = 11.5, 8.9 Hz ), 4.16
(1H, dd, J = 10.3, 6.6 Hz ), 4.04 (1H, m), 3.98 (1H, m), 3.63 (1H, m, CH-O), 3.55 (1H, m,
CH-CN), 2.23 (1H, dd, J = 11.2, 9.5 Hz, N-H), 1.27 (9H, s, Piv), 1.19 (9H, s, Piv), 1.17 (9H,
s, Piv), 1.12 (9H, s, Piv), 0.92 (3H, s, CH3), 0.91 (3H, d, J = 7.0 Hz, CH3), 0.64 (3H, s, CH3);
13C NMR (100 MHz, CDCl3): δ 177.9, 177.7, 177.1, 176.8, 120.5, 88.9, 72.0, 71.8, 71.0, 68.4,
66.9, 61.2, 56.5, 55.9, 48.3, 42.7, 42.1, 40.4, 40.2, 39.1, 38.8, 38.73, 38.69, 36.4, 35.8, 35.5,
35.3, 34.6, 31.70, 31.67, 30.5, 28.3, 27.18, 27.15, 27.08, 26.4, 24.1, 23.3, 20.8, 18.6, 12.0;
HRMS (ESI): m/z calcd for C51H85N2O10 [M+H]+: 885.6204, found: 885.6213.
4.4. Tert-Butyl (R)-2,2-dimethyl-4-vinyloxazolidine-3-carboxylate (11)
To a suspension of methyltriphenylphosphonium bromide (1.87 g, 5.2 mmol) in dry THF (20
mL) was added 2 M standard solution of BuLi in THF (2.6 mL, 5.2 mmol). The mixture was
stirred at room temperature for 1 h under argon atmosphere. A solution of Garner’s aldehyde
10 (1 g, 4.4 mmol) in THF was added dropwise and the reaction mixture was allowed to
stand at rt for 12 h. The solvent was evaporated to dryness, and the residue was dissolved in
CH2Cl2, washed with brine (2 x 15 mL) and water (10 mL), dried over Na2SO4 and
concentrated in vacuo. The crude product was purified by column chromatography (hexane -
1
13
ethyl acetate v/v 20 : 1) and 650 mg (66%) of a colorless oil was isolated. H and C NMR
1
spectra were consistent with literature data.58 IR (ATR, cm-1) ν: 2978, 1694, 1375, 1088; H
NMR (400 MHz, CDCl3, rotamers) δ: 5.77 (m, 1H, =CH-), 5.11 (m, 2H, =CH2), 4.40 (br s,
0.4H, CH-N), 4.27 (br s, 0.6H, CH-N), 4.06 (dd, J = 8.8, 6.1 Hz, 1H, CH2-O), 3.75 (dd, J=8.8,
2.3 Hz, 1H, CH2-O), 1.61 and 1.51 (2s, 6H, C(CH3)2), 1.43 (s, 9H, Boc); 13C NMR (100 MHz,
CDCl3, minor rotamer marked with *) δ: 152.0, 137.4, 136.8*, 116.0*, 115.8, 93.9, 93.6*,
80.2*, 79.6, 68.1, 59.7, 28.4, 27.2*, 26.5, 24.8*, 23.7; HRMS (ESI): m/z calcd for
C12H21NO3Na [M+Na]+: 250.1419, found: 250.1423.
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