3.2.2. General Procedure for Cyclization of Acetylated Thioglycosides to Tetracyclic Conjugates **17a**–**d**–**20a**–**d**

Acetylated thioglycoside, **13a**–**d**–**16a**–**d** (0.25 mM), was suspended in 15 mL of dried MeOH and 0.9 mL MeONa solution (0.5 N) was added. The mixture was stirred at room temperature for 1 h until TLC analysis indicated complete consumption of initial thioglycoside. During the reaction, the formation of a new polar compound precipitate was also observed. The reaction mixture was acidified with 0.25 mL HCl solution (2 N) and the precipitate was filtered off, washed with water, cold MeOH, and gave high purity quinone-tioglycosidic conjugates **17a**–**d**–**20a**–**d**.

*(2R,3S,4S,4aR,12aS)-3,4-Dihydroxy-2-hydroxymethyl-7,10-dimethoxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3 b]pyrano[2,3-e][2,5]oxathiine-6,11-dione* (**17a**); yield 88 mg (86.1%), red solid, R*<sup>f</sup>* 0.35 (C), m.p. 332–335 ◦C27. 1H-NMR(700 MHz, DMSO-*d*6), δ: 3.30 (m, 1H, H-3), 3.47 (m, 3H, H-2, H-4a, H-13a), 3.57 (m, 1H, H-4), 3.74 (m,1H, H-13b), 3.84 (s, 3H, -OCH3), 3.85 (s, 3H, -OCH3), 4.72 (br s, 1H, C13OH), 4.92 (d, 1H, *J* = 8.3 Hz, H-12a), 5.37 (br s, 1H, C3OH), 5.58 (br s, 1H, C4OH), 7.52 (d, 1H, *J* = 9.6 Hz, Ar-H), 7.54 (d, 1H, *J* = 9.6 Hz, Ar-H). 13C-NMR (176 MHz, DMSO-*d*6), δ: 56.7 (-OCH3), 56.8 (-OCH3), 60.8 (C-13), 70.5 (C-3), 73.7 (C-12a), 73.9 (C-4), 79.2 (C-4a), 82.1 (C-2), 118.6, 118.9, 121.7, 122.0, 122.4, 149.7, 153.3, 153.8, 174.7, 179.9. IR (KBr): 3444, 1638, 1614, 1561, 1476, 1405, 1266, 1181, 1075, 935 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C18H18NaO9S 433.0564, found 433.0562.

*(2R,3R,4S,4aR,12aS)-3,4-Dihydroxy-2-hydroxymethyl-7,10-dimethoxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3 b]pyrano[2,3-e][2,5]oxathiine-6,11-dione* (**17b**); yield 95 mg (93%), orange solid, R*<sup>f</sup>* 0.30 (C), m.p. > 350 ◦C. 1H-NMR(500 MHz, DMSO-*d*6), δ: 3.55 (m, 2H, H-13), 3.72 (t, 1H, *J* = 6.0 Hz, H-2), 3.77 (m, 2H, H-4, H-4a), 3.83 (m, 1H, H-3), 3.84 (s, 3H, -OCH3), 3.85 (s, 3H, -OCH3), 4.74 (t, 1H, *J* = 5.6 Hz, C13OH), 4.88 (d, 1H, *J* = 7.6 Hz, H-12a), 4.89 (d, 1H, *J* = 4.6 Hz, C3OH), 5.31 (d, 1H, *J* = 6.3 Hz, C4OH), 7.52 (d, 1H, *J* = 9.7 Hz, Ar-H), 7.55 (d, 1H, *J* = 9.7 Hz, Ar-H). 13C-NMR (125 MHz, DMSO-*d*6), δ: 56.7 (-OCH3), 56.8 (-OCH3), 60.5 (C-13), 69.4 (C-3), 70.4 (C-4), 74.4 (C-12a), 77.7 (C-4a), 80.6 (C-2), 118.6, 118.9, 121.7, 122.0, 122.4, 150.3, 153.3, 153.8, 174.4, 179.8. IR (KBr): 3487, 3289, 3016, 2968, 2935, 2838, 1649, 1611, 1581, 1562, 1476, 1434, 1407, 1384, 1349, 1325, 1267, 1213, 1196, 1180, 1110, 1082, 1056, 1041, 1019, 1008, 936, 904, 873, 824, 803, 755 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C18H18NaO9S 433.0564, found 433.0565.

*(3R,4S,4aR,12aS)-3,4-Dihydroxy-7,10-dimethoxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano[2,3-e][2,5] oxathiine-6,11-dione* (**17c**); yield 80 mg (83.9%), orange solid, *Rf* 0.47 (C), m.p. 329–332 ◦C. 1H-NMR(700 MHz, DMSO-*d*6), δ: 3.37 (m, 1H, H-2a), 3.48 (m, 1H, H-4a), 3.52 (m, 2H, H-3, H-4), 3.84 (s, 3H, -OCH3), 3.85 (s, 3H, -OCH3), 3.91 (dd, 1H, *J* = 11.1, 4.8 Hz, H-2b), 4.85 (d, 1H, *J* = 8.1 Hz, H-12a), 5.38 (d, 1H, *J* = 4.8 Hz, C3OH), 5.61 (d, 1H, *J* = 5.3 Hz, C4OH), 7.52 (d, 1H, *J* = 9.6 Hz, Ar-H), 7.54 (d, 1H, *J* = 9.6 Hz, Ar-H). 13C-NMR (176 MHz, DMSO-*d*6), δ: 56.7 (-OCH3), 56.8 (-OCH3), 70.0 (C-3), 70.3 (C-2), 74.1 (C-4), 74.6 (C-12a), 79.2 (C-4a), 118.6, 118.9, 121.7, 122.1, 122.3, 149.7, 153.4, 153.9, 174.6, 179.8. IR (KBr): 3502, 3470, 3296, 3013, 2981, 2939, 2877, 2836, 1661, 1636, 1611, 1581, 1562, 1478, 1459, 1431, 1408, 1359, 1281, 1267, 1253, 1223, 1196, 1164, 1125, 1095, 1060, 1042, 1023, 975, 935, 887, 818, 797, 755, 718 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C17H16NaO8S 403.0458, found 403.0459.

*(3S,4S,4aR,12aS)-3,4-Dihydroxy-7,10-dimethoxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano[2,3-e][2,5] oxathiine-6,11-dione* (**17d**); yield 88 mg (92.3%), yellow solid, *Rf* 0.43 (C), m.p. 317–320 ◦C. 1H-NMR(700 MHz, DMSO-*d*6), δ: 3.77 (m, 3H, H-2a, H-4, H-4a), 3.84 (m, 1H, H-3), 3.85 (s, 3H, -OCH3), 3.86 (s, 3H, -OCH3), 3.88 (dd, 1H, *J* = 12.2, 1.7 Hz, H-2b), 4.82 (d, 1H, *J* = 7.7 Hz, H-12a), 5.02 (d, 1H, *J* = 4.1 Hz, C3OH), 5.31 (d, 1H, *J* = 6.6 Hz, C4OH), 7.52 (d, 1H, *J* = 9.6 Hz, Ar-H), 7.55 (d, 1H, *J* = 9.6 Hz, Ar-H). 13C-NMR (176 MHz, DMSO-*d*6), δ: 56.7 (-OCH3), 56.8 (-OCH3), 69.4 (C-3), 69.8 (C-4), 71.4 (C-2), 74.8 (C-12a), 77.6 (C-4a), 118.6, 118.9, 121.7, 122.0, 122.4, 150.2, 153.4, 153.8, 174.6, 179.8. IR (KBr): 3496, 3449, 3094, 3012, 2979, 2932, 2864, 2837, 1659, 1642, 1613, 1479, 1459, 1433, 1409, 1352, 1338, 1325, 1280, 1259, 1206, 1188, 1166, 1123, 1097, 1080, 1069, 1048, 1022, 1007, 955, 934, 910, 866, 833, 815, 800, 747 cm−1. HRMS (ESI, *m*/*z*): [M + Na]<sup>+</sup> calcd. for C17H16NaO8S 403.0458, found 403.0453.

*(2R,3S,4S,4aR,12aS)-8,9-Dichloro-3,4-dihydroxy-2-hydroxymethyl-7,10-dimethoxy-3,4,4a,12a-tetrahydro-2Hnaphtho[2,3-b]pyrano[2,3-e][2,5]oxathiine-6,11-dione* (**18a**); yield 100 mg (83.4%), orange solid, R*<sup>f</sup>* 0.51 (C), m.p. 222–224 ◦C27. 1H-NMR(500 MHz, DMSO-*d*6), δ: 3.32 (m, 1H, H-3), 3.50 (m, 2H, H-2, H-13a), 3.54 (m, 1H, H-4a), 3.60 (m, 1H, H-4), 3.75 (m, 1H, H-13b), 3.82 (s, 3H, -OCH3), 3.83 (s, 3H, -OCH3), 4.74 (t, 1H, *J* = 5.3 Hz, C13OH), 4.96 (d, 1H, *J* = 8.1 Hz, H-12a), 5.40 (d, 1H, *J* = 5.7 Hz, C3OH), 5.67 (d, 1H, *J* = 5.8 Hz, C4OH). 13C-NMR (125 MHz, DMSO-*d*6), <sup>δ</sup>: 60.7 (C-13), 61.5 (2 <sup>×</sup> -OCH3), 70.4 (C-3), 73.6 (C-12a), 73.9 (C-4), 79.3 (C-4a), 82.2 (C-2), 123.1, 123.4, 123.9, 135.1, 135.3, 149.9, 152.3, 152.9, 173.4, 178.9. IR (KBr): 3432, 2941, 1653, 1603, 1625, 1458, 1381, 1333, 1275, 1209, 1131, 1025, 951 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C18H16Cl2NaO9S 500.9784, found 500.9784.

*(2R,3R,4S,4aR,12aS)-8,9-Dichloro-3,4-dihydroxy-2-(hydroxymethyl)-7,10-dimethoxy-3,4,4a,12a-tetrahydro-2Hnaphtho[2,3-b]pyrano[2,3-e][2,5]oxathiine-6,11-dione* (**18b**); yield 98 mg (81.7%), orange solid, R*<sup>f</sup>* 0.47 (C), m.p. 276–279 ◦C. 1H-NMR(700 MHz, DMSO-*d*6), δ: 3.56 (m, 2H, H-13), 3.75 (t, 1H, *J* = 6.0 Hz, H-2), 3.79 (dd, 1H, *J* = 9.6, 3.3 Hz, H-4), 3.82 (s, 3H, -OCH3), 3.83 (s, 3H, -OCH3), 3.85 (m, 2H, H-3, H-4a), 4.80 (br s, 2H, 2 <sup>×</sup> OH), 4.92 (d, 1H, *<sup>J</sup>* <sup>=</sup> 7.9 Hz, H-12a), 5.40 (br s, 1H, OH). 13C-NMR (176 MHz, DMSO-*d*6), δ: 60.5 (C-13), 61.5 (2 × -OCH3), 69.5 (C-3), 70.4 (C-4), 74.3 (C-12a), 77.9 (C-4a), 80.8 (C-2), 123.2, 123.4, 123.9, 135.1, 135.2, 150.5, 152.3, 152.9, 173.4, 178.9. IR (KBr): 3413, 2940, 2855, 1652, 1603, 1542, 1524, 1457, 1380, 1336, 1274, 1236, 1207, 1121, 1090, 1024, 945, 876, 839, 805, 762 cm−1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C18H16Cl2NaO9S 500.9784, found 500.9783.

*(3R,4S,4aR,12aS)-8,9-Dichloro-3,4-dihydroxy-7,10-dimethoxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano [2,3-e][2,5]oxathiine-6,11-dione* (**18c**); yield 102 mg (90.7%), orange solid, R*<sup>f</sup>* 0.59 (C), m.p. 277–279 ◦C. 1H-NMR(700 MHz, DMSO-*d*6), δ: 3.40 (m, 1H, H-2a), 3.54 (m, 3H, H-4a, H-4, H-3), 3.81 (s, 3H, -OCH3), 3.83 (s, 3H, -OCH3), 3.93 (dd, 1H, *J* = 11.2, 4.6 Hz, H-2b), 4.90 (d, 1H, *J* = 7.5 Hz, H-12a), 5.42 (d, 1H, *J* = 4.4 Hz, C3OH), 5.72 (d, 1H, *J* = 4.9 Hz, C4OH). 13C-NMR (176 MHz, DMSO-*d*6), <sup>δ</sup>: 61.5 (2 <sup>×</sup> -OCH3), 69.9 (C-3), 70.4 (C-2), 74.0 (C-4), 74.5 (C-12a), 79.4 (C-4a), 123.0, 123.4, 123.8, 135.1, 135.3, 149.9, 152.3, 152.9, 173.4, 178.9. IR (KBr): 3482, 3385, 3003, 2938, 2880, 2855, 1651, 1604, 1544, 1524, 1458, 1382, 1330, 1307, 1272, 1237, 1225, 1208, 1124, 1090, 1074, 1061, 1054, 1024, 975, 948, 898, 869, 838, 816, 802, 763, 741 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C17H14Cl2NaO8S 470.9679, found 470.9673.

*(3S,4S,4aR,12aS)-8,9-Dichloro-3,4-dihydroxy-7,10-dimethoxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano [2,3-e][2,5]oxathiine-6,11-dione* (**18d**); yield 97 mg (86.3%), orange solid, R*<sup>f</sup>* 0.56 (C), m.p. 286–289 ◦C. 1H-NMR(500 MHz, DMSO-*d*6), δ: 3.80 (m, 2H, H-2a, H-4), 3.82 (s, 3H, -OCH3), 3.83 (s, 3H, -OCH3), 3.85 (m, 2H, H-3, H-4a), 3.90 (dd, 1H, *J* = 12.2, 1.7 Hz, H-2b), 4.86 (d, 1H, *J* = 8.1 Hz, H-12a), 5.05 (br s, 1H, C3OH), 5.40 (br s, 1H, C4OH). 13C-NMR (125 MHz, DMSO-*d*6), <sup>δ</sup>: 61.5 (2 <sup>×</sup> -OCH3), 69.4 (C-3), 69.8 (C-4), 71.5 (C-2), 74.7 (C-12a), 77.8 (C-4a), 123.2, 123.4, 123.9, 135.1, 135.2, 150.4, 152.3, 152.9, 173.4, 178.9. IR (KBr): 3391, 2980, 2940, 2856, 1654, 1603, 1543, 1525, 1458, 1381, 1334, 1305, 1272, 1237, 1211, 1128, 1092, 1048, 1026, 967, 944, 913, 876, 839, 805, 757 cm−1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C17H14Cl2NaO8S 470.9679, found 470.9675.

*(2R,3S,4S,4aR,12aS)-3,4,10-Trihydroxy-2-hydroxymethyl-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano[2,3 e][2,5]oxathiine-6,11-dione* (**19a**); yield 86 mg (93.7%), orange solid, R*<sup>f</sup>* 0.56 (C), decomposition > 342 ◦C. 1H-NMR(700 MHz, DMSO-*d*6), δ: 3.32 (m, 1H, H-3), 3.50 (m, 2H, H-2, H-13a), 3.60 (m, 2H, H-4, H-4a), 3.75 (m, 1H, H-13b), 4.74 (t, 1H, *J* = 5.5 Hz, C13OH), 5.01 (d, 1H, *J* = 7.7 Hz, H-12a), 5.41 (d, 1H, *J* = 5.8 Hz, C3OH), 5.69 (d, 1H, *J* = 5.7 Hz, C4OH), 7.30 (dd, 1H, *J* = 8.4, 0.7 Hz, H-9), 7.54 (dd, 1H, *J* = 7.4, 0.7 Hz, H-7), 7.70 (dd, 1H, *J* = 8.4, 7.4 Hz, H-8), 11.52 (s, 1H, C10OH). 13C-NMR (176 MHz, DMSO-*d*6), δ: 60.7 (C-13), 70.4 (C-3), 73.5 (C-12a), 73.9 (C-4), 79.4 (C-4a), 82.3 (C-2), 113.8 (C-10a), 119.2 (C-7), 122.9 (C-11a), 124.2 (C-9), 130.8 (C-6a), 136.5 (C-8), 151.0 (C-5a), 159.8 (C-10), 175.1 (C-6), 186.1 (C-11). IR (KBr): 3464, 3351, 3233, 2955, 2881, 1646, 1616, 1580, 1517, 1477, 1455, 1416, 1383, 1356, 1324, 1297, 1280, 1252, 1229, 1219, 1194, 1165, 1148, 1133, 1092, 1055, 1037, 1000, 973, 889, 863, 836, 828, 816, 755, 728 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C16H14NaO8S 389.0302, found 389.0300.

*(2R,3R,4S,4aR,12aS)-3,4,10-Trihydroxy-2-hydroxymethyl-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano- [2,3-e][2,5]oxathiine-6,11-dione* (**19b**); yield 75 mg (81.7%), dark orange solid, R*<sup>f</sup>* 0.52 (C), decompose above > 346 ◦C. 1H-NMR(500 MHz, DMSO-*d*6), δ: 3.57 (m, 2H, H-13), 3.76 (t, 1H, *J* = 6.0 Hz, H-2), 3.80 (m, 1H, H-4), 3.85 (m, 1H, H-3), 3.90 (t, 1H, *J* = 9.5, 8.0 Hz, H-4a), 4.77 (t, 1H, *J* = 5.6 Hz, C13OH), 4.96 (d, 1H, *J* = 4.8 Hz, C3OH), 4.98 (d, 1H, *J* = 8.0 Hz, H-12a), 5.43 (d, 1H, *J* = 6.8 Hz, C4OH), 7.30 (dd, 1H, *J* = 8.4, 0.9 Hz, H-9), 7.54 (dd, 1H, J = 7.4, 0.9 Hz, H-7), 7.70 (dd, 1H, *J* = 8.4, 7.4 Hz, H-8), 11.53 (s, 1H, C10OH). 13C-NMR (125 MHz, DMSO-*d*6), δ: 60.5 (C-13), 69.5 (C-3), 70.4 (C-4), 74.1 (C-12a), 78.1 (C-4a), 80.8 (C-2), 113.8 (C-10a), 119.2 (C-7), 122.9 (C-11a), 124.2 (C-9), 130.8 (C-6a), 136.5 (C-8), 151.5 (C-5a), 159.8 (C-10), 175.1 (C-6), 186.1 (C-11). IR (KBr): 3456, 3338, 2984, 2938, 2888, 1644, 1616, 1580, 1476, 1456, 1431, 1401, 1384, 1327, 1296, 1279, 1250, 1208, 1165, 1136, 1105, 1085, 1056, 1024, 979, 903, 879, 860, 833, 813, 754, 734, 690 cm−1. HRMS (ESI, *m*/*z*): [M + Na]<sup>+</sup> calcd. for C16H14NaO8S 389.0302, found 389.0295.

*(3R,4S,4aR,12aS)-3,4,10-Trihydroxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano[2,3-e][2,5]oxathiine-6,11 dione* (**19c**); yield 76 mg (90.1%), orange solid, *Rf* 0.67 (C), m.p. 348–350 ◦C with decomposition. 1H-NMR(700 MHz, DMSO-*d*6), δ: 3.41 (m, 1H, H-2), 3.55 (m, 2H, H-3, H-4), 3.60 (m, 1H, H-4a), 3.94 (dd, 1H, *J* = 11.1, 4.7 Hz, H-2- ), 4.95 (d, 1H, *J* = 8.0 Hz, C-12a), 5.42 (d, 1H, *J* = 4.7 Hz, C3OH), 5.73 (d, 1H, *J* = 5.3 Hz, C4OH), 7.30 (dd, 1H, *J* = 8.4, 0.9 Hz, H-9), 7.54 (dd, 1H, *J* = 7.4, 0.9 Hz, H-7), 7.70 (dd, 1H, *J* = 8.4, 7.4 Hz, H-8), 11.51 (s, 1H, C10OH). 13C-NMR (176 MHz, DMSO-*d*6), δ: 70.0 (C-3), 70.4 (C-2), 74.0 (C-4), 74.3 (C-12a), 79.4 (C-4a), 113.8 (C-10a), 119.2 (C-7), 122.8 (C-11a), 124.2 (C-9), 130.8 (C-6a), 136.6 (C-8), 151.0 (C-5a), 159.8 (C-10), 175.1 (C-6), 186.1 (C-11). IR (KBr): 3381, 3300, 2940, 2899, 2867, 1652, 1625, 1621, 1581, 1516, 1475, 1462, 1454, 1417, 1378, 1323, 1306, 1295, 1239, 1222, 1200, 1168, 1146, 1136, 1074, 1056, 1044, 1035, 1002, 976, 962, 900, 868, 833, 818, 789, 756 cm−1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C15H12NaO7S 359.0196, found 359.0197.

*(3S,4S,4aR,12aS)-3,4,10-Trihydroxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano[2,3-e][2,5]oxathiine-6,11 dione* (**19d**); yield 78 mg (92.5%), orange solid, *Rf* 0.62 (C), m.p. 319–321 ◦C. 1H-NMR(500 MHz, DMSO-*d*6), δ: 3.79 (m, 2H, H-4, H-2a), 3.86 (m, 1H, H-3), 3.90 (m, 2H, H-4a, H-2b), 4.91 (d, 1H, *J* = 8.0 Hz, H-12a), 5.10 (d, 1H, *J* = 4.0 Hz, C3OH), 5.44 (d, 1H, *J* = 7.0 Hz, C4OH), 7.30 (dd, 1H, *J* = 8.4, 1.0 Hz, H-9), 7.53 (dd, 1H, *J* = 7.5, 1.0 Hz, H-7), 7.70 (dd, 1H, *J* = 8.4, 7.5 Hz, H-8), 11.54 (s, 1H, C10OH). 13C-NMR (125 MHz, DMSO-*d*6), δ: 69.4 (C-3), 69.7 (C-4), 71.5 (C-2), 74.5 (C-12a), 77.9 (C-4a), 113.8 (C-10a), 119.2 (C-7), 122.9 (C-11a), 124.2 (C-9), 130.7 (C-6a), 136.5 (C-8), 151.4 (C-5a), 159.8 (C-10), 175.1 (C-6), 186.1 (C-11). IR (KBr): 3511, 3196, 2987, 2925, 2892, 1654, 1624, 1578, 1475, 1463, 1444, 1378, 1356, 1333, 1308, 1279, 1237, 1177, 1164, 1139, 1109, 1084, 1071, 1022, 1004, 982, 938, 911, 837, 861, 835, 815, 754 cm<sup>−</sup>1. HRMS (ESI, *m*/*z*): [M + Na]<sup>+</sup> calcd. for C15H12NaO7S 359.0196, found 359.0192.

*(2R,3S,4S,4aR,12aS)-3,4,7-Trihydroxy-2-(hydroxymethyl)-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano-[2,3 e][2,5]oxathiine-6,11-dione* (**20a**); yield 80 mg (87.1%), orange solid, R*<sup>f</sup>* 0.56 (C), m.p. 274–276 ◦C. 1H-NMR(700 MHz, DMSO-*d*6), δ: 3.33 (m, 1H, H-3), 3.50 (m, 2H, H-2, H-13a), 3.60 (m, 2H, H-4, H-4a), 3.75 (m, 1H, H-13b), 4.73 (t, 1H, *J* = 5.6 Hz, C13OH), 5.01 (d, 1H, *J* = 7.7 Hz, H-12a), 5.41 (d, 1H, *J* = 5.7 Hz, C3OH), 5.68 (d, 1H, *J* = 5.7 Hz, C4OH), 7.32 (dd, 1H, *J* = 8.5, 0.9 Hz, H-8), 7.51 (dd, 1H, *J* = 7.4, 0.9 Hz, H-10), 7.70 (dd, 1H, *J* = 8.5, 7.4 Hz, H-9), 11.72 (s, 1H, C7OH). 13C-NMR (176 MHz, DMSO-*d*6), δ: 60.7 (C-13), 70.4 (C-3), 73.6 (C-12a), 73.9 (C-4), 79.2 (C-4a), 82.2 (C-2), 113.4 (C-6a), 118.7 (C-10), 124.1 (C-11a), 124.5 (C-8), 131.2 (C-10a), 136.5 (C-9), 150.0 (C-5a), 160.7 (C-7), 180.4 (C-11), 180.5 (C-6). IR (KBr): 3493, 3474, 3415, 3365, 3264, 2959, 2931, 2892, 1658, 1628, 1585, 1481, 1457, 1403, 1457, 1380, 1296, 1280, 1246, 1223, 1198, 1156, 1143, 1124, 1096, 1077, 1048, 1035, 1009, 952, 895, 869, 834, 816, 796, 747 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C16H14NaO8S 389.0302, found 389.0297.

*(2R,3R,4S,4aR,12aS)-3,4,7-Trihydroxy-2-hydroxymethyl-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano[2,3 e][2,5]oxathiine-6,11-dione* (**20b**); yield 75 mg (81.7%), orange solid, R*<sup>f</sup>* 0.52 (C), m.p. 293–295 ◦C. 1H-NMR(500 MHz, DMSO-*d*6), δ: 3.56 (m, 2H, H-13), 3.76 (t, 1H, *J* = 6.0 Hz, H-2), 3.80 (dd, 1H, *J* = 9.5, 3.2 Hz, H-4), 3.85 (dd, 1H, *J* = 3.3, 1.2 Hz, H-3), 3.89 (d, 1H, *J* = 9.5, 7.9 Hz, H-4a), 4.83 (br s, 3H, C3OH,

C4OH, C13OH), 4.97 (d, 1H, *J* = 7.9 Hz, H-12a), 7.32 (dd, 1H, *J* = 8.5, 1.0 Hz, H-8), 7.51 (dd, 1H, *J* = 7.5, 1.0 Hz, H-10), 7.70 (dd, 1H, *J* = 8.5, 7.5 Hz, H-9), 11.72 (s, 1H, C7OH). 13C-NMR (125 MHz, DMSO-*d*6), δ: 60.5 (C-13), 69.5 (C-3), 70.4 (C-4), 74.2 (C-12a), 77.9 (C-4a), 80.8 (C-2), 113.4 (C-6a), 118.7 (C-10), 124.1 (C-11a), 124.5 (C-8), 131.3 (C-10a), 136.5 (C-9), 150.6 (C-5a), 160.7 (C-7), 180.4 (C-11), 180.5 (C-6). IR (KBr): 3412, 2941, 1627, 1581, 1475, 1454, 1385, 1297, 1282, 1241, 1208, 1192, 1155, 1129, 1074, 1049, 986, 954, 937, 870, 832, 813, 745, 698 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C16H14NaO8S 389.0302, found 389.0296.

*(3R,4S,4aR,12aS)-3,4,7-Trihydroxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano[2,3-e][2,5]oxathiine-6,11 dione* (**20c**); yield 70 mg (83.0%), orange solid, R*<sup>f</sup>* 0.67 (C), m.p. 334–336 ◦C. 1H-NMR(500 MHz, DMSO-*d*6), δ: 3.41 (m, 1H, H-2a), 3.56 (m, 3H, H-3, H-4, H-4a), 3.94 (dd, 1H, *J* = 11.0, 4.7 Hz, H-2b), 4.95 (d, 1H, *J* = 7.5 Hz, H-12a), 5.42 (d, 1H, *J* = 4.8 Hz, C3OH), 5.73 (d, 1H, *J* = 5.1 Hz, C4OH), 7.32 (dd, 1H, *J* = 8.5, 1.0 Hz, H-8), 7.51 (dd, 1H, *J* = 7.5, 1.0 Hz, H-10), 7.70 (dd, 1H, *J* = 8.5, 7.5 Hz, H-9), 11.71 (s, 1H, C7OH). 13C-NMR (125 MHz, DMSO-*d*6), δ: 69.4 (C-3), 69.7 (C-4), 71.5 (C-2), 74.5 (C-12a), 77.9 (C-4a), 113.8 (C-10a), 119.2 (C-7), 122.9 (C-11a), 124.2 (C-9), 130.7 (C-6a), 136.5 (C-8), 151.4 (C-5a), 159.8 (C-10), 180.4 (C-11), 180.5 (C-6). IR (KBr): 3401, 2887, 1653, 1622, 1579, 1476, 1454, 1407, 1390, 1297, 1277, 1251, 1220, 1207, 1194, 1156, 1134, 1090, 1063, 1048, 1008, 976, 952, 902, 840, 831, 818, 745 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C15H12NaO7S 359.0196, found 359.0194.

*(3S,4S,4aR,12aS)-3,4,7-Trihydroxy-3,4,4a,12a-tetrahydro-2H-naphtho[2,3-b]pyrano[2,3-e][2,5]oxathiine-6,11 dione* (**20d**); yield 82 mg (97.3%), dark orange solid, *Rf* 0.62 (C), m.p. 284–286 ◦C. 1H-NMR(500 MHz, DMSO-*d*6), δ: 3.79 (dd, 1H, *J* = 12.7, 3.4 Hz, H-2a), 3.80 (m, 1H, H-3), 3.86 (m, 1H, H-4), 3.89 (t, 1H, *J* = 8.0 Hz, H-4a), 3.91 (dd, 1H, *J* = 12.7, 1.8 Hz, H-2b), 4.90 (d, 1H, *J* = 8.0 Hz, H-12a), 5.08 (d, 1H, *J* = 4.0 Hz, C3OH), 5.41 (d, 1H, *J* = 6.9 Hz, C4OH), 7.32 (dd, 1H, *J* = 8.4, 1.0 Hz, H-8), 7.51 (dd, 1H, *J* = 7.5, 1.0 Hz, H-10), 7.69 (dd, 1H, *J* = 8.4, 7.5 Hz, H-9), 11.72 (s, 1H, C7OH). 13C-NMR (125 MHz, DMSO-*d*6), δ: 69.4 (C-3), 69.7 (C-4), 71.5 (C-2), 74.6 (C-12a), 77.7 (C-4a), 113.4 (C-6a), 118.7 (C-10), 124.1 (C-11a), 124.5 (C-8), 131.2 (C-10a), 136.4 (C-9), 150.5 (C-5a), 160.6 (C-7), 180.3 (C-11), 180.4 (C-6). IR (KBr): 3541, 3268, 3167, 2998, 2936, 1648, 1627, 1621, 1618, 1581, 1474, 1453, 1405, 1384, 1330, 1299, 1284, 1245, 1215, 1191, 1173, 1153, 1115, 1088, 1068, 1049, 1037, 1007, 950, 915, 881, 869, 841, 831, 812, 790, 744, 729 cm<sup>−</sup>1. HRMS (ESI): *m*/*z* [M + Na]<sup>+</sup> calcd. for C15H12NaO7S 359.0196, found 359.0191.

#### *3.3. Biology*

#### 3.3.1. Cell Culture

Human adenocarcinoma cell line HeLa, mouse neuroblastoma cell line Neuro-2a, and mouse epithelial cells Jb6 Cl 41-5a were obtained from ATCC (Manassas, VA, USA). Mouse ascites Ehrlich carcinoma was provided by the N.N. Blokhin NMRCO (Ministry of Health of the Russian Federation, Moscow, Russia).

HeLa and Neuro-2a cells were cultured in DMEM medium containing 10% fetal bovine serum (FBS) (Biolot, Russia) and 1% penicillin/streptomycin (Biolot, Russia). Jb6 Cl 41-5a cells were cultivated in MEM medium containing 5% fetal bovine serum (FBS) (Biolot, Russia) and 1% penicillin/streptomycin (Biolot, Russia). All cell lines were incubated at 37 ◦C in a humidified atmosphere with 5% (*v*/*v*) CO2.

The cells of Ehrlich carcinoma were injected into the peritoneal cavity of 18–20 g albino CD-1 mice (male and female). Cells for experiments were collected 7 days after inoculation. The mice were killed by perivisceral dislocation and the ascitic fluid containing tumor cells was collected with a syringe. The cells were washed three times by centrifugation at 2000 rpm (450 g) for 5 min at 4 ◦C in phosphate-buffered saline (PBS; pH 7.4) followed by resuspension in RPMI-1640 culture medium with 10% FBS.

Erythrocytes were isolated from the blood of mice. Blood was taken from CD-1 mice (18–20 g). The mice were anesthetized with diethyl ether, their chests were rapidly opened, and blood was collected in cold (4 ◦C) 10 mM phosphate-buffered saline pH 7.4 (PBS) without an anticoagulant. Erythrocytes were washed by centrifugation with centrifuge LABOFUGE 400R (Heraeus, Germany) for 5 min 3 times (2000 rpm) in PBS using at least 10 vol. of washing solution. Then, the residue of erythrocytes were resuspended in ice cold phosphate-buffered saline (pH 7.4) to a final optical density of 1.0 at 700 nm and kept on ice.

All experiments were carried out in accordance with the EU Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments.
