Biomolecules 2020, 10, 369
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was purified by flash chromatography using a gradient elution system of 10%–30% EtOAc in
1
hexanes. Compound 8 was obtained as a white solid in 44% yield (0.437 mmol, 138 mg). H NMR (400
MHz, CDCl3) δ ppm 8.50 (s, 1 H), 7.49 (d, J = 8.72 Hz, 1 H), 6.88 (dd, J = 8.67, 2.20 Hz, 1 H), 6.80 (d, J =
2.06 Hz, 1 H), 4.40 (q, J = 7.15 Hz, 2 H), 4.08 (t, J = 6.22 Hz, 2 H), 2.30 (td, J = 6.91, 2.55 Hz, 2 H), 1.97
13
(m, 3 H), 1.74 (tt, J = 7.30 Hz, 2 H), 1.40 (t, J = 7.10 Hz, 3 H). C NMR (100 MHz, CDCl3) δ ppm 164.6,
163.5, 157.6, 157.2, 149.0, 130.7, 114.0, 114.0, 111.6, 100.8, 83.7, 68.9, 68.3, 61.7, 27.9, 24.9, 18.1, 14.3.
+
HRMS (ESI): calcd for C18H18O5Na ([MNa] ): 337.1052, found: 337.1074. mp: 92.6–93.6 °C.
Compound 9: To a solution of 8 (0.437 mmol, 138 mg) dissolved in acetonitrile, NaOH (4.93
mmol, 197 mg, 10 eq) was added as a 2 M solution in water (2.5 mL). The reaction was stirred for 3.5
h after which it was partitioned between water (10 mL), 1 M HCl (10 mL) and EtOAc (30 mL). The
aqueous phase was extracted with EtOAc (3 × 30 mL) and the combined organic phases were dried
with MgSO4. The remaining EtOAc was removed using a rotary evaporator to obtain compound 9 as
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a white solid in 97% yield (0.425 mmol, 122 mg). H NMR (400 MHz, DMSO) δ ppm 12.97 (br. s., 1 H),
8.71 (s, 1 H), 7.82 (d, J = 8.72 Hz, 1 H), 7.01 (m, 2 H), 4.14 (t, J = 6.22 Hz, 2 H), 2.79 (t, J = 2.55 Hz, 1 H),
13
2.24 (td, J = 6.69, 2.20 Hz, 2 H), 1.83 (tt, J = 8.50, 7.70 Hz, 2 H), 1.61 (tt, J = 7.30 Hz, 2 H). C NMR (100
MHz, DMSO) δ ppm 164.1, 163.9, 157.2, 156.8, 148.9, 131.5, 113.7, 113.5, 111.5, 100.6, 84.1, 71.4, 68.0,
+
27.4, 24.4, 17.3. HRMS (ESI): calcd for C16H14O5Na ([MNa] ): 309.0739, found: 309.0727. mp: 170.0–
170.9 °C.
Compound 6: Compound 9 (0.349 mmol, 100 mg) was dissolved in SOCl2 (6 mL). The solution
was brought to reflux and stirred for 6 h before removing excess SOCl2 using the rotary evaporator.
The residue was dissolved in pyridine (5 mL) to which compound 5 (0.349 mmol, 149 mg, 1.0 eq)
dissolved in pyridine (5 mL) was added and the mixture was left to stir overnight. The solution was
then taken up in EtOAc (20 mL) and then washed with 1 M HCl (3 × 20 mL), 5% CuSO4 (20 mL) and
brine (20 mL). The organic layer was dried with MgSO4 and the solvent was removed on a rotary
evaporator to obtain the crude residue, which was purified by flash chromatography using a 5:4:1
hexanes/DCM/EtOAc mixture. Compound 6 was obtained as a pale‐yellow solid in 12% yield (0.0431
1
mmol, 25 mg). H NMR (400 MHz, CDCl3) δ ppm 10.96 (s, 1 H), 8.92 (s, 1 H), 7.85 (d, J = 1.86 Hz, 2 H),
7.62 (d, J = 8.72 Hz, 1 H), 7.28 (t, J = 1.86 Hz, 1 H), 6.96 (dd, J = 8.72, 2.35 Hz, 1 H), 6.89 (d, J = 2.25 Hz,
1 H), 6.50 (q, J = 1.67 Hz, 2 H), 4.11 (t, J = 6.27 Hz, 2 H), 2.31 (td, J = 6.96, 2.65 Hz, 2 H), 2.18 (d, J = 1.86
13
Hz, 6 H), 1.99 (m, 3 H), 1.75 (m, 2 H). C NMR (100 MHz, CDCl3) δ ppm 170.1, 168.9, 164.7, 162.1,
160.1, 156.9, 149.3, 145.9, 138.9, 132.7, 131.2, 127.6, 118.4, 116.4, 114.7, 114.3, 112.4, 100.8, 83.7, 69.0, 68.4,
+
27.9, 24.8, 18.1, 11.2. HRMS (ESI): calcd for C32H25N3O8Na ([MNa] ): 602.1539, found: 602.1550. mp:
decomp. at 192.9–194.2 °C.
Compound 12: To a solution of 3‐aminophenol (1 g, 9.2 mmol, 2.0 eq) in THF (20 mL) was added
4‐ethynylbenzaldehyde. The solution was stirred for 1.5 h at r.t. prior to adding STAB (1.36 g, 6.44
mmol, 1.4 eq). After stirring for 3 h at r.t., the reaction was quenched with sat. NaHCO3 (60 mL) and
extracted with ether (3 × 20 mL). Compound 12 was purified using flash chromatography with a 2:8
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EtOAc/hexanes eluent and obtained as a transparent viscous oil in 75% yield. H NMR (400 MHz,
CDCl3) δ ppm 7.51–7.39 (m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.01 (t, J = 8.0 Hz, 1H), 6.20 (dddd, J = 10.4,
13
8.0, 2.3, 0.8 Hz, 2H), 6.08 (t, J = 2.3 Hz, 1H), 4.32 (s, 2H), 3.06 (s, 1H). C NMR (100 MHz, CDCl3) δ
156.8, 149.6, 140.4, 132.6, 130.4, 127.4, 121.1, 106.2, 104.9, 99.8, 83.6, 48.1. HRMS (EI): calcd for
C15H13NO: 223.09971, found: 223.09831.
Compound 13: Compound 12 (460 mg, 2.06 mmol) was dissolved in MeOH and cooled to 0 °C.
Once cooled, acetaldehyde (4.0 eq, 0.461 mL, 8.24 mmol) was added and the solution was stirred for
2 h. After, the solution was removed from ice and then NaBH4 (6.0 eq., 468 mg, 12.4 mmol) was added
and the mixture stirred at room temperature overnight. Purification by flash chromatography by
gradient elution (0%–30% EtOAc in hexane) yielded compound 13 in 50% yield as a transparent
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viscous oil. H NMR (400 MHz, CDCl3) δ ppm 7.43 (d, J = 8.23 Hz, 2 H), 7.18 (d, J = 7.84 Hz, 2 H), 7.02
(t, J = 8.28 Hz, 1 H), 6.25 (m, 1 H), 6.15 (m, 2 H), 4.62 (s, 1 H), 4.48 (s, 2 H), 3.43 (q, J = 7.09 Hz, 2 H),
13
3.04 (s, 1 H), 1.19 (t, J = 7.05 Hz, 3 H). C NMR (100 MHz, CDCl3) δppm 156.7, 149.9, 140.1, 132.4,
+
130.2, 126.5, 120.5, 105.1, 103.3, 99.2, 83.6, 53.8, 45.4, 12.2. HRMS (ESI): calcd for C17H18NO ([MH] ):
252.1388, found: 252.1362.