3.1.23. ((3*S*,4*S*)-5,8-dihydroxy-4-methoxy-7-nitro-3-pentylisochroman-1-one (**15**)

To a solution of **3** (28.9 mg, 89.1 μmol) in AcOH (0.50 mL) was added the mixture of AcOH and 70% HNO3 (0.80 mL:0.20 mL) at 0 ◦C. After stirring for 10 min at the same temperature, the reaction was quenched by adding saturated aqueous NaHCO3 at 0 ◦C. The mixture was extracted with EtOAc (×3) and the combined organic layers were washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was pathed through SiO2 plug and the resultant mixture of monoMOM nitro derivative **15a** was used for the next reaction without further purification. To a solution of **15a** mixture in MeOH (7.5 mL) was added 6 M aqueous HCl (2.4 mL) at 0 ◦C. After stirring for 5 h at 40 ◦C, the reaction was quenched by adding saturated aqueous NaHCO3 at 0 ◦C. The mixture was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified with PTLC (EtOAc:*n*-hexane = 1:1) to give nitro derivative **15** (21.5 mg, 74%) as a yellow solid. m.p. 158-159; 1H-NMR (400 MHz, CDCl3) δ 11.89 (1H, s), 7.78 (1H, s), 6.80 (1H, br-s), 4.82 (1H, d, *J* = 2.6 Hz), 4.55 (1H, ddd, *J* = 2.6, 5.2, 8.3 Hz), 3.46 (3H, s), 1.96 (1H, m), 1.86 (1H, m), 1.59 (1H, m), 1.47 (1H, m), 1.40–1.25 (4H, overlapped), 0.91 (3H, t, *J* = 7.1 Hz); 13C-NMR (125 MHz, CDCl3) δ 167.5, 150.4, 144.9, 137.6, 129.4, 119.7, 110.7, 81.0, 70.3, 57.6 , 31.4, 29.4, 24.7, 22.4, 14.0; IR (KBr) 3416, 2962, 2927, 2857, 1679, 1445, 1261, 1018, 800 cm<sup>−</sup>1; HRMS (ESI) *m*/*z* (M + H)<sup>+</sup> calculated for (C15H20NO7) <sup>+</sup> 326.1240, found 326.1224.

#### 3.1.24. (3*S*,4*S*)-7-amino-5,8-dihydroxy-4-methoxy-3-pentylisochroman-1-one (**16**)

To a solution of nitro derivative **15** (5.0 mg, 15.4 μmol) in THF (0.62 mL) and MeOH (80 μL) was added PtO2 (0.3 mg, 1.54 μmol) at room temperature. After stirring for 1.5 h at the same temperature under hydrogen atmosphere (1 atm), the mixture was passed through a membrane filter to remove PtO2. The mixture was concentrated under reduced pressure and the residue was purified with PTLC (EtOAc:*n*-hexane = 3:7, developed by three times) to give nitro derivative **16** (4.3 mg, 95%) as a yellow solid. m.p. 118–119 ◦C; 1H-NMR (500 MHz, CDCl3) δ 10.72 (1H, s), 6.45 (1H, s), 5.68 (1H, br-s), 4.67 (1H, d, *J* = 2.5 Hz), 4.46 (1H, ddd, *J* = 2.5, 5.5, 8.3 Hz), 4.05 (1H, br-s), 3.32 (3H, s), 1.94 (1H, m), 1.84 (1H, m), 1.75–1.50 (1H, overlapped), 1.45 (1H, m), 1.40–1.25 (4H, overlapped), 0.90 (3H, t, *J* = 7.0 Hz); 13C-NMR (125 MHz, CDCl3) δ 169.8, 145.9, 144.5, 137.2, 109.8, 108.4, 106.8, 82.4, 69.1, 56.1, 31.6, 30.1, 24.9, 22.5, 14.0; IR (KBr) 3378, 2957, 2926, 2858, 1681, 1464, 1217, 1171 cm<sup>−</sup>1; HRMS (ESI) *m*/*z* (M + Na)<sup>+</sup> calculated for (C15H21NO5Na)<sup>+</sup> 318.1317, found 318.1321.

#### 3.1.25. (3*S*,4*S*)-7-chloro-8-hydroxy-4-methoxy-5-(methoxymethoxy)-3-pentylisochroman-1-one (**18a**)

To a solution of **3** (5.0 mg, 15.4 μmol) in DMF (0.18 mL) was added the solution of *N*-chlorosuccinimide (4.1 mg, 30.8 μmol) in DMF (31 μL) at room temperature. After stirring for 5 h at 65 ◦C, the reaction was quenched by adding saturated aqueous NaHCO3 at 0 ◦C. The mixture was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified with PTLC (EtOAc:*n*-hexane = 1:9) to give monoMOM chloro derivative **18a** (3.3 mg, 60%) as a brown solid. m.p. 79–81 ◦C; 1H-NMR (400 MHz, CDCl3) δ 11.23 (1H, s), 7.55 (1H, s), 5.18 (1H, d, *J* = 7.0 Hz), 5.16 (1H, d, *J* = 7.0 Hz), 4.59 (1H, d, *J* = 1.7 Hz), 4.39 (1H, ddd, *J* = 1.7, 6.0, 8.0 Hz), 3.50 (3H, s), 3.30 (3H, s), 2.07 (1H, m), 1.86 (1H, m), 1.70-1.50 (1H, overlapped), 1.47 (1H, m), 1.45-1.25 (4H, overlapped), 0.92 (3H, t, *J* = 7.1 Hz); 13C-NMR (125 MHz, CDCl3) δ 168.7, 152.8, 146.3, 125.1, 123.6, 123.0, 109.0, 95.7, 82.7, 67.4, 56.8, 56.4, 31.5, 30.4, 24.7, 22.5, 14.0.; IR (KBr) 2955, 2927, 2853, 2826, 1681, 1453, 1433, 1206 cm<sup>−</sup>1; HRMS (ESI) *m*/*z* (M + Na)<sup>+</sup> calculated for (C17H23O6ClNa)<sup>+</sup> 381.1081, found 381.1088.
