Mar. Drugs 2017, 15, 58
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129.34, 128.61, 127.95, 127.51, 114.84, 108.74, 75.41, 70.05, 69.40, 35.59, 31.19, 27.08, 25.83 ppm; HRMS
(ESI) calculated for C20H24O3 [M + Na]+ 335.1725, found 335.1744.
Compound 16 (0.50 g, 1.60 mmol) was dissolved in methanol (10 mL) and cooled to 0 ◦C, after
PTSA (30 mg, 0.16 mmol) was added, the reaction mixture was stirred at room temperature for 16 h.
The reaction solution was concentrated in vacuo, the residue was dissolved in ethyl acetate (50 mL)
and washed with saturated aqueous solution of sodium bicarbonate (50 mL) and brine (50 mL). The
organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was
purified by flash chromatography to afford the desired diol compound S1 (0.43 g, 99%) as clear oil.
20
[
α
]
=
−
14.7 (c 1.0, MeOH); 1H-NMR (500 MHz, CDCl3)
δ 7.47–7.29 (m, 5H), 7.12 (d, J = 8.5 Hz, 2H),
D
6.91 (d, J = 8.6 Hz, 2H), 5.04 (s, 2H), 3.78–3.57 (m, 2H), 3.46 (dd, J = 11.1, 7.6 Hz, 1H), 2.80–2.55 (m, 2H),
2.28 (s, 1H), 2.08 (s, 1H), 1.72 (m, 2H). 13C NMR (125 MHz, CDCl3)
δ
157.16, 137.20, 134.01, 129.33,
129.31, 128.57, 128.55, 127.89, 127.47, 127.44, 114.92, 114.88, 77.27, 77.01, 76.76, 71.52, 70.12, 66.82, 34.87,
30.90 ppm; HRMS (ESI) calculated for C17H20O3 [M + Na]+ 295.1412, found 295.1456.
Diol compound S1 (136 mg, 0.50 mmol) was dissolved in DCM (5 mL) and cooled to 0 ◦C, after
triethyl amine (0.35 mL, 2.5 mmol) and triphenylmethyl chloride (0.15 g, 0.53 mmol) were added, the
reaction mixture was stirred at room temperature for 4 h. The reaction was diluted with DCM (50 mL)
and extracted with brine (50 mL). Layers were separated, the organic phase was dried over anhydrous
sodium sulfate, concentrated in vacuo, and purified by flash chromatography to afford compound 17
(0.24 g, 93%) as clear oil. [α] δ 7.52–7.21 (m, 20H),
20 = 2.7 (c 1.0, CHCl3); 1H-NMR (500 MHz, CDCl3)
D
7.09 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.5 Hz, 2H), 5.06 (s, 2H), 3.81 (s, 1H), 3.21 (dd, J = 9.4, 3.3 Hz, 1H), 3.09
(dd, J = 9.4, 7.3 Hz, 1H), 2.74–2.52 (m, 2H), 2.36 (s, 1H), 1.83–1.64 (m, 2H). 13C-NMR (125 MHz, CDCl3)
δ 157.08, 143.90, 137.30, 134.31, 129.37, 128.72, 128.59, 127.90, 127.48, 127.15, 114.83, 86.73, 70.23, 70.12,
67.71, 35.20, 30.83 ppm; HRMS (ESI) calculated for C36H34O3 [M + Na]+ 537.2508, found 537.2553.
To a solution of compound 17 (0.43 g, 0.84 mmol) dissolved in THF (3 mL), NaH (0.1g, 4.17 mmol)
was added at 0 ◦C. The reaction mixture was stirred at 0 ◦C for 0.5 h, then benzyl bromide (0.15 mL,
1.25 mmol) was added. Upon completion of the addition, the reaction mixture was brought to room
temperature and stirred for 16 h. The reaction was quenched by saturated aqueous solution of NH4Cl
(5 mL). Volatiles were removed in vacuo. The residue was extracted with ethyl acetate (50 mL × 2).
The combined organic phases were washed with brine (50 mL), dried over anhydrous sodium sulfate
and concentrated in vacuo. The residue was purified by flash chromatography to give the desired
20
fully protected compound S2 (0.48 g, 95%) as clear oil. [
CDCl3)
J = 11.6 Hz, 1H), 4.50 (d, J = 11.6 Hz, 1H), 3.54 (dt, J = 9.2, 4.7 Hz, 1H), 3.21 (qd, J = 9.9, 4.8 Hz, 2H),
2.67–2.48 (m, 2H), 1.93–1.80 (m, 2H). 13C-NMR (100 MHz, CDCl3)
156.95, 144.13, 138.88, 137.24,
α
]
=
−
2.3 (c 1.0, CHCl3); 1H-NMR (400 MHz,
D
δ
7.56–7.17 (m, 25H), 7.09 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.5 Hz, 2H), 5.04 (s, 2H), 4.71 (d,
δ
134.58, 129.32, 128.75, 128.56, 128.35, 127.88, 127.77, 127.47, 126.94, 114.71, 86.61, 77.73, 72.04, 70.06,
65.79, 34.02, 30.71 ppm; HRMS (ESI) calculated for C43H40O3 [M + Na]+ 627.2977, found 627.2941.
The above intermediate S2 (0.50 g, 0.83 mmol) was dissolved in methanol–DCM (4 mL, 1:1) and
cooled to 0 ◦C. After PTSA (16 mg, 0.08 mmol) was added, the reaction mixture was stirred at room
temperature for 4 h. Then the reaction was concentrated in vacuo. The residue was purified by flash
20
chromatography to produce compound 18 (0.21 g, 71%). [
CDCl3)
2H), 3.75 (dd, J = 11.2, 3.1 Hz, 1H), 3.64–3.48 (m, 2H), 2.66 (ddd, J = 8.8, 6.6, 4.7 Hz, 2H), 2.03–1.76 (m,
2H). 13C-NMR (100 MHz, CDCl3)
157.08, 138.38, 137.18, 134.17, 129.27, 128.57, 128.53, 127.92, 127.86,
α
]
= 2.0 (c 1.1, CHCl3); 1H-NMR (400 MHz,
D
δ
7.49–7.29 (m, 10H), 7.09 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.5 Hz, 2H), 5.06 (s, 2H), 4.66–4.53 (m,
δ
127.83, 127.48, 114.85, 78.96, 71.58, 70.08, 64.13, 32.81, 30.70 ppm; HRMS (ESI) calculated for C24H26O3
[M + Na]+ 385.1882, found 385.1920.
◦
Compound 18 (0.21 g, 0.59 mmol) was dissolved in DCM–H2O (3 mL, 2:1) at 0 C. DAIB (16
mg, 0.08 mmol) and TEMPO (5 mg, 0.29 mmol) were sequentially added, the reaction mixture was
stirred in dark for 16 h at room temperature. The reaction was diluted by DCM (50 mL) and washed
with brine (20 mL). The organic layer was separated, dried over sodium sulfate, and concentrated in
vacuo. The residue was purified by flash chromatography to provide acid S-2 (0.19 g, 84%) as clear oil.