SUPPLEMENTARY MATERIAL

SUPPLEMENTARY MATERIAL Valuable Building Block for the Synthesis of Lunularic Acid, Hydrangeic Acid and their Analogues Ramesh Mukkamla a, Asik Hossain a & Indrapal Singh Aidhen a * a Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India E-mail address: isingh@iitm.ac.in. Corresponding author: Tel. 0091-44-22574219; Fax: 0091-44 22574202 Abstract: A new functionalized sulfone based building block has been synthesized that enabled C-C bond formation through Julia olefination. The utility of developed building block was demonstrated by successful synthesis of two natural products Lunularic acid, Hydrangeic acid and initial libraries of their analogues. Keywords: Lunularic acid; Hydrangeic acid; Amorfrutin; Cajaninstilbene acid; Julia olefination; bi-benzyl natural products. 1

Table of contents S.No Title Page Numbers 1 General procedure 3 2 Synthesis of 5-((benzo[d]thiazol-2ylthio) methyl)-2, 2-dimethyl- 4H-benzo[d][1,3]dioxin-4-one (13) 3 3 Synthesis of 5-((benzo[d]thiazol-2-ylsulfonyl) methyl)-2,2-3-4 dimethyl-4h-benzo[d][1,3]dioxin-4-one (9) 4 General procedure for olefination of building block 9 with 4 aldehydes (14a-i) 5 Spectral description for 15a-i 5-9 6 General procedure for hydrolysis of the olefinated compounds 15ai 9-12 and Spectral description for 8 &18a-h 7 General procedure for hydrogenation of intermediates 15a-i and 12-16 Spectral description for 16a-h 8 General procedure for hydrolysis of compounds 16a-h and Spectral 16-19 description for 7&17a-f 9 1 H-NMR and 13 C-NMR spectra 20-54 2

Experimental section: General procedure: All the reactions were carried out by oven dried glassware under an inert atmosphere of nitrogen. Tetrahydrofuran was dried and distilled over Na Ph 2 CO, whereas, dichloromethane (CH 2 Cl 2 ) and N, N-dimethylformamide (DMF) were distilled over Calcium hydride. Thinlayer chromatography was performed on pre-coated silica gel F 254 aluminium plates with visualization under short UV light or by staining with Hanessian reagent. Melting points were obtained using a melting point apparatus and are uncorrected. NMR experiments were recorded on BRUKER AV 400 and 500 FT NMR instrument operating at 400 and 500 MHz respectively using tetramethylsilane (TMS) as the internal standard. HRMS were recorded on a MICRO Q TOF mass spectrometer by using ESI technique at 10 ev. Synthesis of 5-((benzo[d]thiazol-2ylthio) methyl)-2, 2-dimethyl-4H-benzo[d][1,3]dioxin- 4-one (13): To a solution of 12 (2.64 g, 9.79 mmol), 2-mercaptobenzothiazole (1.96 g, 11.75 mmol) in CH 2 Cl 2 (25 ml) at 0 C was added triethylamine (2.74 ml, 19.58 mmol), then stirring was continued at room temperature and progress of the reaction was monitored by TLC, after complete consumption of starting material the reaction mixture was diluted with water (50 ml) then extracted in to CH 2 Cl 2 (3 x 30 ml). The combined organic layers were washed with water (50 ml), brine (50 ml), and dried over anhydrous sodium sulphate and then filtered. The filtrate was concentrated under vacuum; the resulting crude product was purified by silica gel column chromatography gave the sulphide 13 as white crystalline solid. Yield = 3.15g (91%); mp = 135-137 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.89 (d, J = 8.0 Hz, 1H, BTH); 7.71 (d, J = 8.0 Hz, 1H, BTH); 7.43-7.36 (m, 3H, ArH); 7.29-7.25 (m, 1H, ArH); 6.88 (dd, J 1 = 7.6 Hz, J 2 = 2.0 Hz, 1H, ArH); 5.05 (s, 2H, CH 2 ); 1.72 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 167.0 (C); 160.7 (C); 157.4 (C); 153.2 (C); 142.2 (C); 135.5 (CH); 126.0 (CH); 125.8 (CH); 124.3 (CH); 121.6 (CH); 121.1 (CH); 117.3 (CH); 111.7 (C); 105.8 (C); 35.6 (CH 2 ); 25.8 (CH 3 ) ppm. HRMS-ESI: Calcd. For C 18 H 16 N O 3 S 2 [M+H]: 358.0572 found 358.0562. Synthesis of 5-((benzo[d]thiazol-2-ylsulfonyl) methyl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (9): To a solution of compound 13 in methanol (30 ml) was added sodium 3

tungstate dihydrate (Na 2 WO 4 2H 2 O) (1.975 g, 6.01 mmol), 30% hydrogen peroxide (H 2 O 2 ) (9 ml, 90.15 mmol) and stirred at room temperature for 12 h. After complete consumption of starting material, methanol in reaction mixture was evaporated under reduced pressure and the reaction residue was dissolved in water (50 ml) and extracted into CH 2 Cl 2 (3 x 40 ml). The combined organic layers were dried over anhydrous sodium sulphate, filtered and the filtrate was concentrated under reduced pressure. The obtained crude product was purified by silica-gel column chromatography provided the building block 9 as white crystalline solid. Yield = 2.039 g (87%); mp = 167 168 C. 1 H NMR (400 MHz, CDCl 3 ) δ: 8.21 (d, J = 8.4 Hz, 1H, BTH); 7.96 (d, J = 8.4 Hz, 1H, BTH); 7.62 (m, 1H, BTH); 7.57 (m, 1H, BTH); 7.42 (t, J = 7.6 Hz, 1H, ArH); 7.03 (d, J = 7.6 Hz, 1H, ArH); 7.00 (d, J = 8.4 Hz, 1H, ArH); 5.62 (s, 2H, CH 2 ); 1.68 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 165.7 (C); 160.6 (C); 157.4 (C); 152.6 (C); 137.2 (C); 135.4 (CH); 129.6 (C); 128.2 (CH); 127.9 (CH); 127.7 (CH); 125.6 (CH); 122.4 (CH); 119.1 (CH); 114.0 (C); 106.2 (C); 57.6 (CH 2 ); 25.5 (CH 3 ) ppm. HRMS-ESI: Calcd. For C 18 H 16 N O 5 S 2 [M+H]: 390.0470 found 390.0486. General procedure for olefination of building block 9 with aldehydes (14a-i): To a solution of building block 9 (0.2 g, 0.51 mmol) in dry DMF (3 ml) at 0 º C, under nitrogen atmosphere was added sodium hydride (0.04 g, 0.769 mmol). The solution turned reddish orange colour indicating the formation of carbanion. After 5 min of stirring, corresponding aldehydes (14a-i) (0.765 mmol) was added directly. The temperature of the reaction was gradually raised from 0 C to room temperature and stirring continued at room temperature for 4-5 h. The progress of the reaction was monitored by TLC and after complete consumption of starting material; the reaction mixture was quenched with saturated NH 4 Cl (15 ml) solution followed by extracted with ethyl acetate (3 x 15 ml). The combined organic extracts were washed with 10% aqueous solution of NaOH (3 x 15 ml) to remove by-product hydroxybenzothiazole, followed by water (20 ml), brine (20 ml) and dried over anhydrous sodium sulphate, filtered, and the filtrate was concentrated under vacuum. The obtained crude compounds were subjected to column chromatography using silica gel as stationary phase, and combination of hexane/ethyl acetate as mobile phase gave the protected olefinated products 15a-i as presented below. 4

(E)-4-(2-(2, 2-dimethyl-4oxo-4H-benzo[d] [1, 3] dioxin-5-yl) vinyl) phenyl acetate (15a): Yield = 132 mg (76%); R f = 0.4 in 30% EtOAc/Hexane; 1 H NMR (400 MHz, CDCl 3 ) δ: 8.21 (d, J = 16.0 Hz, 1H, CH); 7.57 (d, J = 8.4 Hz, 2H, ArH); 7.48 (t, J = 8.0 Hz, 1H, ArH); 7.39 (d, J = 7.6 Hz, 1H, ArH); 7.1 7.08 (m, 2H, ArH); 7.05 (d, J = 16.4 Hz, 1H, CH); 6.88 6.86 (m, 1H, ArH); 2.30 (s, 3H, COCH 3 ); 1.72 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 169.5 (C); 160.6 (C); 157.1 (C); 150.6 (C); 141.9 (C); 135.3 (CH); 135.0 (C); 131.7 (CH); 128.2 (CH); 127.1 (CH); 121.9 (CH); 121.1 (CH); 116.4 (CH); 111.1 (C); 105.4 (C); 25.7 (CH 3 ); 21.2 (CH 3 ) ppm. IR (KBr Pellet): 1765, 1721, 1602, 1471, 1364, 1323, 1275, 1187, 1050, and 1016 cm -1. HRMS-ESI: Calcd. For C 20 H 18 O 5 Na [M+Na]: 361.1052 found 361.1056. (E)-5-(2-(benzo[d] [1, 3] dioxol-5-yl) vinyl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (15b): Yield = 165 mg (98%); R f = 0.4 (EtOAc-Hexane 2:8); mp = 131 132 C 1 H NMR (400 MHz, CDCl 3 ) δ: 8.10 (d, J = 16.0 Hz, 1H, CH); 7.46 (t, J = 8.0 Hz, 1H, ArH); 7.37 (d, J = 7.6 Hz, 1H, ArH); 7.14 (s, 1H, ArH); 6.99 (d, J = 16.4 Hz, 1H, CH) ; 6.98 (d, J = 7.6 Hz, 1H, ArH); 6.84 (d, J = 8.0 Hz, 1H, ArH); 6.79 (d, J = 8.0 Hz, 1H, ArH); 5.97 (s, 2H, CH 2 ); 1.72 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.6 (C); 157.0 (C); 148.3 (C), 147.9 (C), 142.1 (C); 135.2 (CH); 132.5 (CH); 131.8 (C); 125.1 (CH); 122.4 (CH); 120.8 (CH); 116.0 (C); 110.9 (C); 108.4 (CH); 106.3 (CH); 105.3 (C); 101.3 (CH 2 ); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 3084, 2897, 1727, 1593, 1577, 1493, 1471, 1442, 1381, 1318, 1253, 1226, 1044, 964, 930, and 776 cm -1. HRMS-ESI: Calcd. For C 19 H 17 O 5 [M+H]: 325.1076 found 325.1068. 5

(E)-5-(4-methoxystyryl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (15c): Yield = 88 mg (56%); R f = 0.5 in 30% EtOAc/Hexane; mp = 109 110 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 8.15 (d, J = 16.4 Hz, 1H, CH); 7.52 (d, J = 8.8 Hz, 2H, ArH); 7.46 (t, J = 8.0 Hz, 1H, ArH); 7.40 (d, J = 8.0 Hz, 1H, ArH), 7.05 (d, J = 16.4 Hz, 1H, CH); 6.9 (d, J = 8.8 Hz, 2H, ArH); 6.84 (d, J = 7.6 Hz, 1H, ArH); 3.82 (s, 3H, OCH 3 ); 1.72 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.7 (C); 159.8 (C); 157.0 (C); 142.3 (C); 135.2 (CH); 132.5 (CH); 130.0 (C); 128.6 (CH); 124.6 (CH); 120.8 (CH); 115.8 (CH); 114.2 (CH); 110.8 (C); 105.2 (C); 55.4 (CH 3 ); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 2993, 1727, 1595, 1509, 1467, 1387, 1322, 1248, 1176, 1041, 957, 922, and 821 cm -1. HRMS-ESI: Calcd. For C 19 H 19 O 4 [M+H]: 311.1283 found 311.1278. (E)-5-(4-butoxystyryl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (15d): Yield = 122 mg (68%); R f = 0.6 in 30% EtOAc/Hexane; mp = 101 102 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 8.15 (d, J = 16.0 Hz, 1H, CH); 7.49 (d, J = 6.8 Hz, 2H, ArH); 7.46 (t, J = 8.0 Hz, 1H, ArH); 7.40 (dd, J 1 = 8.0 Hz, J 2 = 0.8 Hz, 1H, ArH); 7.05 (d, J = 16.0 Hz, 1H, CH); 6.89 (d, J = 6.8 Hz, 2H, ArH); 6.83 (dd, J 1 = 7.8 Hz, J 2 = 1.6 Hz, 1H, ArH); 3.98 (t, J = 6.4 Hz, 2H, OCH 2 ); 1.81-1.74 (m, 2H, Alkyl CH 2 ); 1.72 (s, 6H, 2 x CH 3 ); 1.54-1.45 (m, 2H, Alkyl CH 2 ); 0.98 (t, J = 7.6 Hz, 3H, Alkyl CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.7 (C); 159.5 (C); 157.1 (C); 142.5 (C); 135.2 (CH); 132.6 (CH); 129.8 (C); 128.6 (CH); 124.5 (CH); 120.8 (CH); 115.7 (CH); 114.8 (CH); 110.9 (C); 105.3 (C); 67.9 (OCH 2 ); 31.4 (CH 2 ); 25.8 (2 x CH 3 ); 19.3 (CH 2 ); 13.9 (CH 3 ) ppm. IR (KBr Pellet): 2959, 2926, 2360, 1723, 1596, 1509, 1467, 1386, 1318, 1249, 1042, 960 cm -1. HRMS-ESI: Calcd. For C 22 H 24 O 4 Na [M+Na]: 375.1572 found 375.1576. (E)-2, 2-dimethyl-5-(4-(octyloxy)styryl)-4H-benzo[d][1,3]dioxin-4-one (15e): 6

Yield = 116 mg (55%); R f = 0.7 in 30% EtOAc/Hexane; mp = 83 84 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 8.15 (d, J = 16.0 Hz, 1H, CH); 7.51-7.49 (m, 2H, ArH); 7.46 (t, J = 8.0 Hz, 1H, ArH); 7.40 (dd, J 1 = 7. 8 Hz, J 2 = 0.8 Hz, 1H, ArH); 7.05 (d, J = 16.4 Hz, 1H, CH); 6.89 (d, J = 8.8 Hz, 2H, ArH); 6.83 (dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, 1H, ArH); 3.97 (t, J = 6.8 Hz, 2H, OCH 2 ); 1.82-1.75 (m, 2H, Alkyl CH 2 ); 1.72 (s, 6H, 2 x CH 3 ); 1.48-1.29 (m, 10H, 5 x CH 2 ); 0.89 (t, J = 7.2 Hz, 3H, Alkyl CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.7 (C); 159.5 (C); 157.1 (C); 142.4 (C); 135.1 (CH); 132.6 (CH); 129.8 (C); 128.6 (C); 128.5 (CH); 128.5 (C); 124.4 (CH); 120.8 (CH); 115.7 (CH); 114.9 (C); 114.8 (CH); 114.8 (C); 110.9 (C); 105.2 (C); 68.2 (OCH 2 ); 31.9 (CH 2 ); 29.5 (CH 2 ); 29.4 (CH 2 ); 29.3 (CH 2 ); 26.1 (CH 2 ); 25.8 (CH 3 ); 22.8 (CH 2 ); 14.2 (CH 3 ) ppm. IR (KBr Pellet): 2920, 2852, 1724, 1598, 1509, 1472, 1384, 1351, 1321, 1272, 1248, 1204, 1172, 1044, 830, 776 cm -1. HRMS-ESI: Calcd. For C 26 H 32 O 4 Na [M+Na]: 431.2198 found 431.2202. (E)-5-(3, 4-dichlorostyryl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (15f): Yield = 158 mg (89 %); R f = 0.6 in 30% EtOAc/Hexane; mp = 103-104 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 8.22 (d, J = 16.0 Hz, 1H, CH); 7.62 (d, J = 1.6 Hz, 1H, ArH); 7.5 (t, J = 7.8 Hz, 1H, ArH); 7.41-7.4 (m, 3H, ArH); 6.93 (d, J = 16.0 Hz, 1H, CH); 6.91 (d, J = 8.2 Hz, 1H, ArH); 1.73 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.6 (C); 157.1 (C); 141.2 (C); 137.4 (C); 135.5 (CH); 132.9 (C); 131.8 (C); 130.7 (CH); 130.2 (CH); 128.9 (CH); 126.2 (CH); 121.2 (CH); 116.9 (CH); 111.2 (C); 105.5 (C); 25.8 (CH 3 ) ppm. IR (KBr Pellet): 1724, 1595, 1477, 1384, 1352, 1318, 1273, 1046, 814, 774 cm -1. HRMS-ESI: Calcd. For C 18 H 14 O 3 Na Cl 2 [M+Na]: 371.0218 found 371.0227. (E)-5-(2, 4-difluorostyryl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (15g): 7

Yield = 74 mg (91%); R f = 0.6 in 30% EtOAc/Hexane; mp = 119 120 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 8.22 (d, J = 16.4 Hz, 1H, CH); 7.7 (m, 1H, ArH); 7.49 (t, J = 8.0 Hz, 1H, ArH); 7.4 (d, J = 7.6 Hz, 1H, ArH); 7.18 (d, J = 16.4 Hz, 1H, CH); 6.9-6.81 (m, 3H, ArH); 1.73 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ:162.9 (dd, 1 J 1C-F = 210 Hz, 2 J 2C-F = 12 Hz, C); 160.6 (C); 160.2 (dd, 1 J 1C-F = 170 Hz, 2 J 2C-F = 12 Hz, C); 157.1 (C); 141.7 (C); 135.4 (CH); 128.5 128.3 (m, CH); 123.6 (C); 121.6 121.5 (m, C); 121.3 (CH); 116.7 (CH); 111.8 (dd, J 1 = 21.5 Hz, J 2 = 4 Hz, CH); 111.1 (C); 105.4 (C); 104.1 (m, CH); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 2361, 2338, 1725, 1592, 1499, 1470, 1385, 1319, 1267, 1234, 1210, 1043, 965, 846, 808, 774 cm -1. HRMS-ESI: Calcd. For C 18 H 14 O 3 K F 2 [M+K]: 355.0548 found 355.0567. (E)-5-(4-(benzyloxy)styryl)-2,2-dimethyl-4-methylene-4H-benzo[d][1,3]dioxin-4-one (15h): Yield = 118 mg (76%); R f = 0.6 in 30% EtOAc/Hexane; mp = 137 138 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 8.16 (d, J = 16.4 Hz, 1H, CH); 7.52 (d, J = 8.8 Hz, 2H, ArH); 7.49-7.33 (m, 7H, ArH); 7.05 (d, J = 16.4 Hz, 1H, CH); 6.98 (d, J = 8.8 Hz, 2H, ArH); 6.85 (d, J = 8.0 Hz, 1H, ArH); 5.09 (s, 2H, CH 2 ); 1.73 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.7 (C); 159.1 (C); 157.1 (C); 142.4 (C); 136.9 (C); 135.2 (CH); 132.5 (CH); 130.3 (C); 128.7 (CH); 128.6 (CH); 128.1 (CH); 127.6 (CH); 124.8 (CH); 120.8 (CH); 115.8 (CH); 115.2 (CH); 110.9 (C); 105.3 (C); 70.1 (CH 2 ); 25.8 (CH 3 ) ppm. IR (KBr Pellet): 1719, 1596, 1509, 1468, 1386, 1352, 1321, 1250, 1043, 998 cm -1. HRMS-ESI: Calcd. For C 25 H 23 O 4 [M+H]: 387.1596 found 387.1598. (E)-2, 2-dimethyl-5-(3, 4, 5-trimethoxystyryl)-4H-benzo[d] [1, 3] dioxin-4one (15i): Yield = 184 mg (99 %); R f = 0.3 in 20% EtOAc/Hexane; mp = 120 121 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 8.15 (d, J = 16.0 Hz, 1H, CH); 7.46 (d, J = 8.0 Hz, 1H, ArH); 7.39 (d, J = 7.6 Hz, 1H, ArH); 7.00 (d, J = 16.4 Hz, 1H, CH); 6.86 (dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, 1H, ArH); 8

6.79 (s, 2H, ArH); 3.90 (s, 6H, 2 x OCH 3 ); 3.86 (s, 3H, OCH 3 ); 1.72 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.7 (C); 157.1 (C); 153.5 (C); 141.9 (C); 138.5 (C); 135.3 (CH); 133.0 (C); 132.7 (CH); 126.4 (CH); 121.0 (CH); 116.2 (CH); 111.0 (C); 105.4 (C); 104.3 (CH); 61.0 (CH 3 ); 56.2 (CH 3 ); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 3000, 2929, 2361, 2337, 1724, 1583, 1504, 1472, 1385, 1344, 1321, 1241, 1125, 1045, 775 cm -1. HRMS-ESI: Calcd. For C 21 H 23 O 6 [M+H]: 371.1495 found 371.1502. General procedure for hydrolysis of the olefinated compounds 15a-i: The general hydrolysis procedure was followed on all the substrates; (15a-i) is illustrated with substrate 15b as a representative example. The compound 15b (0.149 mg, 0.46 mmol) dissolved in THF (3 ml) followed by KOH (128.8 mg, 2.3 mmol) solution in 3 ml of water was added. The reaction mixture was refluxed for overnight, cooled to room temperature, acidified to ph 1, and extracted with EtOAc (3 x 10 ml). The combined organic layers were, washed with brine, dried over Na 2 SO 4 and concentrated. The obtained crude compound was purified by column chromatography gave the hydrolysed product (18a). (E)-2-hydroxy-6-(4-hydroxystyryl) benzoic acid (8): Yield = 130 mg (80%); R f = 0.1 in 40% EtOAc-Hexane; mp = 140 142 C; 1 H NMR (500 MHz, CD 3 OD) δ: 7.60 (d, J = 16.0 Hz, 1H, -CH); 7.35 7.29 (m, 3H); 7.12 (d, J = 7.6 Hz, 1H, ArH); 6.86 (d, J = 16.0 Hz, 1H, -CH); 6.80 6.76 (m, 3H) ppm. 13 C NMR (125 MHz, CD 3 OD) δ: 174.3 (C); 161.8 (C); 158.5 (C); 142.0 (C); 133.9 (CH); 131.6 (CH); 130.7 (C); 129.0 (CH); 126.9 (CH); 119.0 (CH); 116.5 (CH) ppm. IR (KBr Pellet): 3451, 1594, 1483, 1446, 1380, 1352, 1255, 1213, 1039, 932 cm -1. Positive mode ESI-MS (m/z): 257 (M+H)+. (E)-2-(2-(benzo[d] [1, 3] dioxol-5yl) vinyl)-6-hydroxybenzoic acid (18a): Yield = 130 mg (75%); R f = 0.1 in 40% EtOAc-Hexane; mp = 127 128 C; 1 H NMR (400 MHz, DMSO-d 6 ) δ: 7.24 (t, J = 8.0 Hz, 1H, ArH); 7.22 (d, J = 16.0 Hz, 1H, CH); 7.14 (d, J = 8.0 Hz, 1H, ArH); 7.09 (d, J = 1.2 Hz, 1H, ArH); 7.03 (d, J = 16.4 Hz, 1H, CH); 6.98 (dd, J 1 = 8.2 Hz, J 2 = 1.2 Hz, 1H, ArH); 6.92 (d, J = 8.0 Hz, 1H, ArH); 6.79 (d, J = 8.0 Hz, 1H, ArH); 6.04 (s, 2H, CH 2 ) ppm. 13 C NMR (100 MHz, DMSO-d 6 ) δ: 170.1 (C); 156.5 (C); 147.8 (C); 9

147.1 (C); 136.5 (C); 131.5 (C); 130.6 (CH); 129.9 (CH); 125.0 (CH); 121.3 (CH); 119.7 (C); 116.1 (CH); 114.8 (CH); 108.5 (CH); 105.4 (CH); 101.1 (CH 2 ) ppm. IR (KBr Pellet): 3451, 1594, 1483, 1446, 1380, 1352, 1255, 1213, 1039, 932 cm -1. HRMS-ESI: Calcd. For C 16 H 12 O 5 [M+Na]: 307.0582 found 307.0566. (E)-2-hydroxy-6-(4-methoxystyryl) benzoic acid (18b): Yield = 52 mg (70%); R f = 0.1 in 40% EtOAc-Hexane; 1 H NMR (400 MHz, DMSO-d 6 ) δ: 7.44 (d, J = 7.6 Hz, 2H, ArH); 7.26-7.10 (m, 4H, ArH); 6.95 (d, J = 7.6 Hz, 2H, ArH); 6.83-6.82 (m, 1H, ArH); 3.77 (s, 3H, OCH 3 ) ppm. 13 C NMR (100 MHz, DMSO-d 6 ) δ: 159.1 (C); 136.3 (C); 130.6 (CH); 130.0 (CH); 129.5 (C); 127.7 (CH); 123.9 (CH); 116.1 (CH); 114.7 (CH); 114.2 (CH); 55.1 (CH 3 ) ppm. IR (KBr Pellet): 3446, 2833, 1665, 1592, 1509, 1461, 1375, 1292, 1235, 1174, 1118, 1017, 826, 778 cm -1. HRMS-ESI: Calcd. For C 16 H 14 O 4 K [M+K]: 309.0529 found 309.0531. (E)-2-(4-butoxystyryl)-6-hydroxybenzoic acid (18c): Yield = 104 mg (79%); R f = 0.1 in 30% EtOAc/Hexane; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.70 (d, J = 16.0 Hz, 1H, CH); 7.45-7.40 (m, 3H, ArH); 7.11 (d, J = 7.6 Hz, 1H, ArH); 6.93 (d, J = 8.4 Hz, 1H, ArH); 6.89 (d, J = 8.4 Hz, 2H, ArH); 6.83 (d, J = 16.0 Hz, 1H, CH); 3.98 (t, J = 6.4 Hz, 2H, CH 2 ); 1.79-1.74 (m, 2H, CH 2 ); 1.53-1.47 (m, 2H, CH 2 ); 0.98 (t, J = 7.2 Hz, 3H, CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 175.6 (C); 163.3 (C); 159.3 (C); 142.9 (C); 135.5 (CH); 131.5 (CH); 130.0 (C); 128.2 (CH); 127.2 (CH); 119.8 (CH); 116.9 (CH); 114.9 (CH); 114.8 (C); 67.9 (CH 2 ); 31.4 (CH 2 ); 19.3 (CH 2 ); 13.9 (CH 3 ) ppm. IR (KBr Pellet): 3443, 2957, 2930, 2361, 2336, 1653, 1596, 1510, 1458, 1380, 1352, 1254, 1137, 968, 827 cm -1. HRMS-ESI: Calcd. For C 19 H 21 O 4 [M+H]: 313.1440 found 313.1423. (E)-2 hydroxy-6-(4-(octyloxy)styryl)benzoic acid (18d): 10

Yield = 53 mg (73%); R f = 0.1 in 30% EtOAc/Hexane; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.69 (d, J = 16.0 Hz, 1H, CH); 7.45-7.41 (m, 3H, ArH); 7.12 (d, J = 7.6 Hz, 1H, ArH); 6.93 (d, J = 8.4 Hz, 1H, ArH); 6.90 (d, J = 8.4 Hz, 2H, ArH); 6.84 (d, J = 16.0 Hz, 1H, CH); 3.98 (t, J = 6.4 Hz, 2H, OCH 2 ); 1.81-1.75 (m, 2H, CH 2 ); 1.47-1.26 (m, 10H, 5 x CH 2 ); 0.89 (t, J = 4.0 Hz, 3H, CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 175.6 (C); 163.4 (C); 159.3 (C); 142.9 (C); 135.6 (CH); 131.5 (CH); 130.0 (C); 128.2 (CH); 127.1 (CH); 119.9 (CH); 116.9 (CH); 114.9 (CH); 109.6 (C); 68.3 (CH 2 ); 31.9 (CH 2 ); 29.5 (CH 2 ); 29.4 (CH 2 ); 26.1 (CH 2 ); 22.8 (CH 2 ); 14.2 (CH 3 ) ppm. IR (KBr Pellet): 3445, 2960, 2933, 2363, 2326, 1663, 1598, 1510, 1459, 1381, 1353, 1255, 1138, 967, 828 cm -1. HRMS-ESI: Calcd. For C 23 H 28 O 4 K [M+K]: 407.1623 found 407.1625. (E)-2-(3, 4-dichlorostyryl)-6-hydroxybenzoic acid (18e): Yield = 50 mg (53%); R f = 0.1 in 30% EtOAc/Hexane; 1 H NMR (400 MHz, DMSO-d 6 ) δ:7.75 (s, 1H, ArH); 7.62 (d, J = 8 Hz, 1H, ArH); 7.50 (d, J = 8 Hz, 1H, ArH); 7.36 (d, J = 16.4 Hz, 1H, CH); 7.30 (t, J = 7.6 Hz, 1H, ArH); 7.19 (d, J = 7.2 Hz, 1H, ArH); 7.10 (d, J = 16 Hz, 1H, CH); 6.86 (d, J = 7.6 Hz, 1H, ArH) ppm. 13 C NMR (100 MHz, DMSO-d 6 ) δ: 176.9 (C); 169.8 (C); 156.3 (C); 137.8 (C); 135.8 (C); 131.5 (C); 131.0 (CH); 130.9 (CH); 129.9 (C); 128.9 (CH); 128.2 (CH); 127.8 (CH); 126.2 (CH); 116.7 (CH); 115.7 (CH) ppm. HRMS-ESI: Calcd. For C 15 H 11 O 3 Cl 2 [M+H]: 309.0072 found 309.0085. (E)-2-(2, 4-difluorostyryl)-6-hydroxybenzoic acid (18f): Yield = 61 mg (83%); R f = 0.1 in 40% EtOAc/Hexane; mp = 138-140 C; 1 H NMR (400 MHz, DMSO-d 6 ) δ:7.68 (d, J = 6.4 Hz, 1H, ArH); 7.47 7.46 (bs, 1H, ArH); 7.29-7.24 (m, 2H); 7.19 (d, J = 7.6 Hz, 1H, ArH); 7.14 7.06 (m, 2H); 6.90 (d, J = 7.2 Hz, 1H, ArH) ppm. 13 C NMR (100 MHz, DMSO-d 6 ) δ:161.8 (dd, 1 J 1C-F = 182 Hz, 2 J 2C-F = 13 Hz, C); 159.3 (dd, 1 J 1C-F = 184 Hz, 2 J 2C-F = 13 Hz, C); 136.2 (C); 130.9 (CH); 129.5 (CH); 129.2 129.1 (m, CH); 129.0 (C); 121.6 (CH); 121.3 (C); 121.2 (C); 116.5 (CH); 115.8 (CH); 112.0 (dd, J 1 = 11

21 Hz, J 2 =3 Hz, CH); 104.2 (t, J = 26 Hz, CH) ppm. HRMS-ESI: Calcd. For C 15 H 10 O 3 F 2 Na [M+Na]: 299.0496 found 299.0468. (E)-2-(4-(benzyloxy)styryl)-6-hydroxybenzoic acid (18g): Yield = 110 mg (88%); R f = 0.1 in 50% EtOAc/Hexane; mp = 128 130 C; 1 H NMR (500 MHz, CD 3 OD) δ: 7.73 (d, J = 16.0 Hz, 1H, -CH); 7.41-7.40 (m, 4H); 7.34 (t, J = 7.0 Hz, 2H, ); 7.30 7.27 (m, 2H); 7.10 (d, J = 7.5 Hz, 1H, ArH); 6.92 (d, J = 8.5 Hz, 2H, ArH); 6.85 (d, J = 16.0 Hz, 1H, -CH); 6.79 (d, J = 8.0 Hz, 1H, ArH); 5.04 (s, 2H, -OCH 2 Ph) ppm. 13 C NMR (125 MHz, CD 3 OD) δ: 162.0 (C); 159.8 (C); 141.9 (C); 138.5 (C); 133.8 (CH); 132.1 (C); 131.0 (CH); 129.4 (CH); 128.9 (CH); 128.8 (CH); 128.5 (CH); 128.2 (CH); 119.1 (CH); 116.6 (CH); 116.0 (CH); 71.0 (CH 2 ) ppm. IR (KBr Pellet): 3452, 1651, 1589, 1505, 1455, 1418, 1343, 1250, 1128, 1028, 997, 960, 830, 773 cm -1. Positive mode ESI-MS (m/z): 347 (M+H) +. (E)-2-hydroxy-6-(3, 4, 5-trimethoxystyryl) benzoic acid (18h): Yield = 95 mg (72%); R f = 0.1 in 40% EtOAc/Hexane; mp = 155 156 C; 1 H NMR (400 MHz, DMSO-d 6 ) δ: 7.31 (d, J = 16.0 Hz, 1H, CH); 7.25 (t, J = 8.0 Hz, 1H, ArH); 7.15 (d, J = 7.6 Hz, 1H, ArH); 7.03 (d, J = 16.4 Hz, 1H, CH); 6.82-6.80 (m, 3H, ArH); 3.81 (s, 6H, 2 x OCH 3 ); 3.67 (s, 3H, OCH 3 ) ppm. 13 C NMR (100 MHz, DMSO-d 6 ) δ: 170.0 (C); 156.4 (C); 153.0 (C); 137.5 (C); 136.5 (C); 132.7 (C); 130.7 (CH); 130.3 (CH); 126.2 (CH); 119.8 (C); 116.3 (CH); 114.9 (CH); 103.8 (CH); 60.0 (CH 3 ); 55.8 (CH 3 ) ppm. IR (KBr Pellet): 3452, 1651, 1589, 1505, 1455, 1418, 1343, 1250, 1128, 1028, 997, 960, 830, 773 cm -1. HRMS-ESI: Calcd. For C 18 H 19 O 6 [M+H]: 331.1182 found 331.1172. General procedure for hydrogenation of intermediates 15a-i: The general hydrogenation procedure was followed on all the substrates; 15a-h is illustrated with substrate 15b as a representative example. To a solution of 15b (81 mg, 0.25 mmol) in MeOH (2 ml), 10% Pd/C (26.6 mg, 0.025 mmol) was added. Then de-gassed the reaction mixture with H 2, and then stirred the reaction mixture at room temperature under hydrogen 12

atmosphere (balloon) for overnight. After complete hydrogenation, the catalyst was filtered through celite pad; obtained filtrate was evaporated under reduced pressure to get reduced compound 16b. 4-(2-(2, 2-dimethyl-4-oxo-4H-benzo[d] [1, 3] dioxin-5yl) ethyl) phenyl acetate (16a): Yield = 47 mg (99%); R f = 0.4 in 30% EtOAc/Hexane; mp = 67-69 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.38 (t, J = 8.0 Hz, 1H, ArH); 7.26-7.24 (m, 2H, ArH); 6.98 (d, J = 8.4Hz, 2H, ArH); 6.86 (d, J = 7.6 Hz, 1H, ArH); 6.83-6.81(m, 1H, ArH); 3.38-3.34(m, 2H, CH 2 ); 2.90-2.86 (m, 2H, CH 2 ); 2.28 (s, 3H, CH 3 ); 1.69 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 169.8 (C); 160.4 (C); 157.3 (C); 148.9 (C); 146.9 (C); 139.4 (C); 135.3 (CH); 129.7 (CH); 125.5 (CH); 121.4 (CH); 115.7 (CH); 112.2 (C); 105.2 (C); 36.9 (CH 2 ); 36.8 (CH 2 ); 25.7 (CH 3 ); 21.2 (CH 3 ) ppm. IR (KBr Pellet): 1762, 1725, 1598, 1381, 1351, 1317, 1272, 1216, 1193, 1050, 1013, 915 cm -1. HRMS-ESI: Calcd. For C 20 H 20 O 5 Na [M+Na] 363 1208 found 363.1219. (E)- (2-benzo[d] [1, 3] dioxol-5yl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (16b): Yield = 53 mg (66%); R f = 0.6 in 30% EtOAc/Hexane; mp = 96 97 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.38 (t, J = 8.0 Hz, 1H, ArH); 6.87-6.77 (m, 3H, ArH); 6.72-6.66 (m, 2H, ArH); 5.90 (s, 2H, CH 2 ); 3.33 (t, J = 8.0 Hz, 2H, CH 2 ); 2.81 (t, J = 8.0 Hz, 2H, CH 2 ); 1.69 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.4 (C); 157.3 (C); 147.6 (C); 147.0 (C); 145.7 (C); 135.7 (C); 135.3 (CH); 125.5 (CH); 121.5 (CH); 115.6 (CH); 112.2 (C); 109.3 (CH); 108.1 (CH); 105.2 (C); 100.8 (CH 2 ); 37.3 (CH 2 ); 37.1 (CH 2 ); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 2922, 2817, 1726, 1608, 1588, 1499, 1481, 1444, 1382, 1353, 1309, 1240, 1045, 925, 855, 806, 771 cm -1. HRMS-ESI: Calcd. For C 19 H 19 O 5 [M+H] 327.1232 found 327.1247. 13

5-(4-methoxyphenethyl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (16c): Yield = 71 mg (90%); R f = 0.6 in 30% EtOAc/Hexane; mp = 91 92 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.37 (t, J = 8.0 Hz, 1H, ArH); 7.15 (d, J = 8.4 Hz, 2H, ArH); 6.86-6.80 (m, 4H, ArH); 3.78 (s, 3H, OCH 3 ); 3.59 (t, J = 7.6 Hz, 2H, CH 2 ); 2.84 (t, J = 8.0 Hz, 2H, CH 2 ); 1.69 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.4 (C); 157.9 (C); 157.2 (C); 147.2 (C); 135.2 (CH); 133.9 (C); 129.7 (CH); 125.5 (CH); 115.5 (CH); 113.8 (CH); 112.2 (C); 105.1 (C); 55.3 (OCH 3 ); 36.9 (CH 2 ); 36.7 (CH 2 ); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 2949, 2831, 1724, 1604, 1584, 1511, 1479, 1380, 1353, 1322, 1258, 1057, 923, 828 cm -1. HRMS- ESI: Calcd. For C 19 H 21 O 4 [M+H]: 313.1440 found 313.1426. 5-(4-butoxyphenethyl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (16d): Yield = 74 mg (82%); R f = 0.5 in 30% EtOAc/Hexane; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.37 (t, J = 7.6 Hz, 1H, ArH); 7.13 (d, J = 8.4 Hz, 2H, ArH); 6.84 (d, J = 7.6 Hz, 1H, ArH); 6.81-6.79 (m, 3H, ArH); 3.39 (t, J = 6.4 Hz, 2H, OCH 2 ); 3.35 (t, J = 7.6 Hz, 2H, CH 2 ); 2.83 (t, J = 8.4 Hz, 2H, CH 2 ); 1.78-1.71 (m, 2H, CH 2 ); 1.69 (s, 6H, 2 x CH 3 ); 1.53-1.43 (m, 2H, CH 2 ); 0.97 (t, J = 7.6 Hz, 3H, CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.4 (C); 157.5 (C); 157.3 (C); 147.3 (C); 135.2 (CH); 133.8 (C); 129.6 (CH); 125.6 (CH); 115.5 (CH); 114.5 (CH); 112.3 (C); 105.2 (C); 67.8 (OCH 2 ); 37.0 (CH 2 ); 36.7 (CH 2 ); 31.5 (CH 2 ); 25.8 (CH 3 ); 19.4 (CH 2 ); 14.0 (CH 3 ) ppm. IR (KBr Pellet): 2936, 2869, 1725, 1600, 1510, 1475, 1385, 1351, 1315, 1264, 1239, 1048, 824 cm -1. HRMS-ESI: Calcd. For C 22 H 26 O 4 Na [M+Na]: 377.1729 found 377.1717. 2, 2-dimethyl-5-(4-(octyloxy) phenethyl)-4h-benzo[d] [1, 3] dioxin-4-one (16e): 14

Yield = 80 mg (99%); R f = 0.7 in 30% EtOAc/Hexane; mp = 69 70 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.37 (t, J = 8.0 Hz, 1H, ArH); 7.14 7.12 (m, 2H, ArH); 6.85 (d, J = 8.0 Hz, 1H, ArH); 6.82 6.79 (m, 3H, ArH); 3.92 (t, J = 6.8 Hz, 2H, OCH 2 ); 3.37 3.33 (m, 2H, CH 2 ); 2.85 2.81 (m, 2H, CH 2 ); 1.79 1.72 (m, 2H, CH 2 ); 1.69 (s, 6H, 2 x CH 3 ); 1.36 1.25 (m, 10H, 5 x CH 2 ); 0.90 0.87 (m, 3H, CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.4 (C); 157.5 (C); 157.3 (C); 147.3 (C); 135.2 (CH); 133.7 (C); 129.6 (CH); 125.6 (CH); 115.5 (CH); 114.4 (CH); 112.3 (C); 105.2 (C); 68.1 (CH 2 ); 37.0 (CH 2 ); 36.7 (CH 2 ); 31.9 (CH 2 ); 29.5 (CH 2 ); 29.4 (CH 2 ); 29.3 (CH 2 ); 26.2 (CH 2 ); 25.7 (CH 3 ); 22.8 (CH 2 ); 14.2 (CH 3 ) ppm. IR (KBr Pellet): 2924, 2853, 1720, 1602, 1582, 1509, 1476, 1388, 1377, 1351, 1321, 1260, 1240, 1056, 818 cm -1. HRMS-ESI: Calcd. For C 26 H 34 O 4 Na [M+Na]: 433.2355 found 433.2355. 5-(3, 4-dichlorophenethyl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (16f): Yield = 66 mg (83%); R f = 0.6 in 30% EtOAc/Hexane; mp = 109 110 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.39 (t, J = 8.0 Hz, 1H, ArH); 7.33-7.31 (m, 2H, ArH); 7.09 (dd, J 1 = 8.4 Hz, J 2 = 2.0 Hz, 1H, ArH); 6.84 (d, J = 7.6 Hz, 2H, ArH); 3.32 (t, J = 8.0 Hz, 2H, CH 2 ); 2.84 (t, J = 7.6 Hz, 2H, CH 2 ); 1.69 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 160.4 (C); 157.4 (C); 146.2 (C); 142.1 (C); 135.5 (CH); 132.2 (C); 130.7 (CH); 130.3 (CH); 129.9 (C); 128.3 (CH); 125.5 (CH); 116.0 (CH); 112.1 (C); 105.3 (C); 36.6 (CH 2 ); 36.5 (CH 2 ); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 1725, 1599, 1472, 1387, 1352, 1308, 1131, 1049 cm -1. HRMS- ESI: Calcd. For C 18 H 16 O 3 Na Cl 2 [M+Na] 373.0374 found 373.0370. 5-(2, 4-difluorophenethyl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (16g): Yield = 73 mg (82%); R f = 0.6 in 30% EtOAc/Hexane; mp = 75 76 C; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.35 (t, J = 8.0 Hz, 1H, ArH); 7.22-7.16 (m, 1H, ArH); 6.83-6.69 (m, 4H, ArH); 3.34 (t, J = 7.2 Hz, 2H, CH 2 ); 2.91 (t, J = 8.0 Hz, 2H, CH 2 ); 1.70 (s, 6H, 2 x CH 3 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ:161.5 (dd, 1 J 1C-F = 240 Hz, 2 J 2C-F = 12 Hz, C); 161.0 (dd, 1 J 1C-F = 245 Hz, 2 J 2C-F = 12 Hz, C); 157.3 (C); 146.3 (C); 135.3 (CH); 131.7 131.6 (m, CH); 125.6 15

(CH); 124.4 (C); 124.3 (C); 124.2 (C); 115.8 (CH); 112.2 (C); 111.0 (dd, J 1 = 20.5 Hz, J 2 = 3 Hz, CH); 105.3 (C); 103.7 (t, J = 26 Hz, CH); 35.3 (CH 2 ); 29.6 (CH 2 ); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 1725, 1603, 1587, 1503, 1479, 1383, 1353, 1321, 1273, 1204, 1132, 1060, 961, 808 cm -1. HRMS-ESI: Calcd. For C 18 H 16 O 3 F 2 Na [M+Na] 341.0965 found 341.0940. 5-(4-hydroxyphenethyl)-2, 2-dimethyl-4H-benzo[d] [1, 3] dioxin-4-one (16h): Yield = 59 mg (98%); R f = 0.3 in 30% EtOAc/Hexane; mp = 151 152 C; 1 H NMR (500 MHz, CDCl 3 ) δ: 7.39 (t, J = 8.0 Hz, 1H, ArH); 7.09 (d, J = 8.5 Hz, 2H, ArH); 6.88 (d, J = 7.5 Hz, 1H, ArH); 6.82 (d, J = 8.0 Hz, 1H, ArH); 6.77 (d, J = 8.5 Hz, 2H, ArH); 5.7 (s, 1H, OH); 3.35 (t, J = 8.0 Hz, 2H, CH 2 ); 2.82 (t, J = 7.5 Hz, 2H, CH 2 ); 1.69 (s, 6H, 2 x CH 3 ) ppm.. 13 C NMR (125 MHz, CDCl 3 ) δ: 160.9 (C); 157.3 (C); 154.1 (C); 147.3 (C); 135.4 (CH); 133.7 (C); 129.8 (C); 129.8 (CH); 129.7 (C); 125.5 (CH); 115.5 (CH); 115.3 (CH); 112.1 (C); 105.3 (C); 37.0 (CH 2 ); 36.8 (CH 2 ); 25.7 (CH 3 ) ppm. IR (KBr Pellet): 3330, 2361, 2338, 1710, 1602, 1517, 1478, 1448, 1384, 1478, 1448, 1384, 1350, 1316, 1264, 1051, 828 cm -1. HRMS-ESI: Calcd. For C 18 H 19 O 4 [M+H] 299.1283 found 299.1269. General procedure for hydrolysis of compounds 16a-h The general hydrolysis procedure was followed on all the substrates; (16a-h) is illustrated with substrate 16a as a representative example. The compound 16a (46 mg, 0.14 mmol) in THF (2 ml) was added KOH (39.2 mg, 0.70 mmol) solution in H 2 O (2 ml). Then the reaction mixture was refluxed for overnight, cooled to room temperature, neutralized with 5% HCl, and extracted with EtOAc (3 x 10 ml). The combined organic extracts were dried over anhydrous Na 2 SO 4 and concentrated. The crude compound was purified by column chromatography provided the titled compound (17a). 2-hydroxy-6-(4-hydroxyphenethyl) benzoic acid (7): Yield = 40 mg (83%); R f = 0.1 in 30% EtOAc/Hexane; mp = 172-174 C; 1 H NMR (400 MHz, DMSO-d 6 ) δ:9.12 (bs, 1H, OH); 7.17 7.13 (m, 1H, ArH); 6.98 (d, J = 7.6 Hz, 2H, ArH); 6.72 (d, J = 7.6 Hz, 1H, ArH); 6.69-6.65 (m, 3H, ArH); 2.83-2.81 (m, 2H, CH 2 ); 16

2.70-2.68 (m, 2H, CH 2 ) ppm. 13 C NMR (100 MHz, DMSO-d 6 ) δ: 170.4 (C); 156.3 (C); 155.3 (C); 141.0 (C); 131.7 (C); 130.7 (CH); 128.9 (CH); 120.2 (CH); 115.0 (CH); 113.8 (CH); 36.4 (CH 2 ) ppm. IR (KBr Pellet): 3462, 1648, 1596, 1513, 1448, 1354, 1245, 1203, 825, 771 cm -1. Negative mode ESI-MS (m/z): 257 (M-H)-. 2-(2-(benzo[d] [1, 3] dioxol-5-yl) ethyl)-6-hydroxybenzoic acid (17a): Yield = 30 mg (75%); R f = 0.1 in 30% EtOAc/Hexane; 1 H NMR (500 MHz, DMSO-d 6 ) δ: 7.16 (t, J = 7.5 Hz, 1H, ArH); 6.79 (d, J = 8.0 Hz, 1H, ArH); 6.77 (s, 1H, ArH); 6.75 (d, J = 8.0 Hz, 1H, ArH); 6.64 (d, J = 8.0 Hz, 1H, ArH); 5.95 (s, 2H, CH 2 ); 2.86 (bs, 2H, CH 2 ); 2.719 (bs, 2H, CH 2 ) ppm. 13 C NMR (125 MHz, DMSO-d 6 ) δ: 170.3 (C); 156.6 (C); 147.2 (C); 145.3 (C); 140.8 (C); 135.6 (C); 130.8 (C); 128.7 (C); 121.0 (CH); 120.3 (CH); 114.0 (CH); 108.6 (CH); 108.1 (CH); 100.6 (CH 2 ); 36.9 (CH 2 ); 36.5 (CH 2 ) ppm. HRMS-ESI: Calcd. For C 16 H 14 O 5 Na [M+Na] 309.0739 found 309.0748. 2-hydroxy-6-(4-methoxyphenethyl) benzoic acid (17b): Yield = 42 mg (77%); R f = 0.1 in 30% EtOAc/Hexane; mp = 116-118 C; 1 H NMR (400 MHz, CDCl 3 ) δ:7.35 (t, J = 8.0 Hz, 1H, ArH); 7.11 (d, J = 8.4 Hz, 2H, ArH); 6.90 (d, J = 8.0 Hz, 1H, ArH); 6.83 (d, J = 8.4Hz, 2H, ArH); 6.74 (d, J =7.6Hz, 1H, ArH); 3.79 (s, 3H, OCH 3 ); 3.29-3.25 (m, 2H, CH 2 ); 2.89-2.85 (m, 2H, CH 2 ) ppm. 13 C NMR (100 MHz, CDCl 3 ) δ: 175.6 (C); 163.7 (C); 157.9 (C); 146.5 (C); 135.6 (CH); 134.0 (C); 129.5 (CH); 123.1 (CH); 116.3 (CH); 113.9 (CH); 110.7 (C); 55.4 (CH 3 ); 38.9 (CH 2 ); 37.5 (CH 2 ) ppm. IR (KBr Pellet): 3449, 2929, 2362, 1659, 1602, 1512, 1467, 1378, 1285, 1242, 1214, 1180, 1117, 1024, 822, 760 cm -1. HRMS-ESI: Calcd. For C 16 H 16 O 4 Na [M+Na] 295.0946 found 295.0940. 2-(4-butoxyphenethyl)-6-hydroxybenzoic acid (17c): 17

Yield = 49 mg (87%); R f = 0.1 in 30% EtOAc/Hexane; mp = 112-114 C; 1 H NMR (500 MHz, CDCl 3 ) δ: 7.31-7.29 (m, 1H, ArH); 7.07 (d, J = 8.0 Hz, 2H, ArH); 6.87 (d, J = 8.0 Hz, 1H, ArH); 6.78 (d, J = 8.0 Hz, 2H, ArH); 6.70 (d, J = 7.5 Hz, 1H, ArH); 3.92 (t, J = 6.5 Hz, 2H, OCH 2 ); 3.24 (t, J = 7.5 Hz, 2H, CH 2 ); 2.83 (t, J = 7.5 Hz, 2H, CH 2 ); 1.77-1.67 (m, 2H, CH 2 ); 1.50-1.44 (m, 2H, CH 2 ); 0.97 (t, J = 7.5 Hz, 3H, CH 3 ) ppm. 13 C NMR (125 MHz, CDCl 3 ) δ: 175.5 (C); 163.4 (C); 157.5 (C); 146.4 (C); 135.3 (CH); 133.8 (C); 129.4 (CH); 123.1 (CH); 116.2 (CH); 114.5 (CH); 114.3 (C); 67.8 (CH 2 ); 38.8 (CH 2 ); 37.4 (CH 2 ); 31.5 (CH 2 ); 19.3 (CH 2 ); 14.0 (CH 3 ) ppm. IR (KBr Pellet): 3455, 2957, 2933, 2360, 2337, 1598, 1511, 1460, 1381, 1352, 1300, 1243, 822 cm -1. HRMS-ESI: Calcd. For C 19 H 22 O 4 Na [M+Na] 337.1416 found 337.1416. 2-hydroxy-6-(4-(octyloxy) phenethyl) benzoic acid (17d): Yield = 38 mg (62%); R f = 0.1 in 30% EtOAc/Hexane; mp = 82 84 C; 1 H NMR (500 MHz, CDCl 3 ) δ: 7.35 (t, J = 8.0 Hz, 1H, ArH); 7.09 (d, J = 8.0 Hz, 2H, ArH); 6.89 (d, J = 8.5 Hz, 1H, ArH); 6.82 (d, J = 8.5 Hz, 2H, ArH); 6.73 (d, J = 7.0 Hz, 1H, ArH); 3.92 (t, J = 6.5 Hz, 2H, OCH 2 ); 3.26 (t, J = 7.5 Hz, 2H, CH 2 ); 2.85 (t, J = 8.5 Hz, 2H, CH 2 ); 1.77-1.74 (m, 2H, CH 2 ); 1.44-1.28 (m, 10H, 5 x CH 2 ); 0.88 (t, J = 6.5 Hz, 3H, CH 3 ) ppm. 13 C NMR (125 MHz, CDCl 3 ) δ: 175.4 (C); 163.7 (C); 157.5 (C); 146.5 (C); 135.6 (CH); 133.8 (C); 129.4 (CH); 123.1 (CH); 116.3 (CH); 114.5 (CH); 110.6 (C); 68.2 (CH 2 ); 38.9 (CH 2 ); 37.5 (CH 2 ); 31.9 (CH 2 ); 29.5 (CH 2 ); 29.4 (CH 2 ); 26.2 (CH 2 ); 22.8 (CH 2 ); 14.2 (CH 3 ) ppm. HRMS-ESI: Calcd. For C 23 H 30 O 4 Na [M+Na] 393.2042 found 393.2029. 2-(3, 4-dichlorophenethyl)-6-hydroxybenzoic acid (17e): Yield = 47 mg (88%); R f = 0.1 in 30% EtOAc/Hexane; 1 H NMR (400 MHz, DMSO-d 6 ) δ:7.51 (d, J = 8.0 Hz, 1H, ArH); 7.43 (s, 1H, ArH); 7.18-7.14 (m, 2H, ArH); 6.77 (d, J = 8.0 Hz, 1H, ArH); 6.68 (d, J = 7.2 Hz, 1H, ArH); 2.91 (bs, 2H, CH 2 ); 2.82 (bs, 2H, CH 2 ) ppm. 13 C NMR (100 MHz, DMSO-d 6 ) δ: 156.7 (C); 142.8 (C); 140.3 (C); 130.9 (CH); 130.7 (C); 18

130.3 (CH); 130.2 (CH); 128.6 (CH); 120.4 (CH); 114.2 (CH); 35.9 (CH 2 ); 35.5 (CH 2 ) ppm. HRMS-ESI: Calcd. For C 15 H 13 O 3 Cl 2 [M+H] 311.0242 found 311.0261. 2-(2, 4-difluorophenethyl)-6-hydroxybenzoic acid (17f): Yield = 42 mg (79%); R f = 0.1 in 30% EtOAc/Hexane; mp = 140-142 C; 1 H NMR (400 MHz, DMSO-d 6 ) δ: 7.29 7.28(bs, 1H, ArH); 7.16 7.09 (m, 2H, ArH); 6.98 (bs, 1H, ArH); 6.75 (d, J = 7.2 Hz, 1H, ArH); 6.62 (d, J = 7.2 Hz, 1H, ArH); 2.95 (bs, 2H, CH 2 ); 2.82 (bs, 2H, CH 2 ) ppm. 13 C NMR (100 MHz, DMSO-d 6 ) δ: 172.3 (C); 161.9 161.8 (m, C); 159.4 (C); 140.7 (C); 131.6 131.4 (CH); 130.7 (CH); 124.4 (C); 120.1 (CH); 114.4 (CH); 110.0 (d, J = 21 Hz, CH); 103.4 (t, J = 26 Hz, CH); 34.5 (CH 2 ); 29.5 (CH 2 ) ppm. HRMS-ESI: Calcd. For C 15 H 12 O 3 F 2 Na [M+Na] 301.0652 found 301.0647. 19

167.01 153.25 157.38 160.73 142.20 105.85 111.73 117.30 121.11 121.62 124.30 125.80 126.07 135.57 76.84 77.16 77.48 35.61 25.80 1.22 3.13 0.98 0.98 0.99 1.98 6.00 5.058 6.873 6.878 6.892 6.897 7.254 7.257 7.260 7.272 7.274 7.275 7.292 7.295 7.366 7.371 7.385 7.390 7.409 7.412 7.428 7.431 7.708 7.709 7.711 7.728 7.729 7.731 7.879 7.880 7.881 7.899 7.900 7.902 1.724 11 10 9 8 7 6 5 4 3 2 1 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 20

165.77 152.66 157.46 160.67 106.21 113.99 119.15 122.44 125.67 127.73 127.95 128.16 129.57 135.40 137.18 76.84 77.16 77.48 57.65 25.55 1.00 1.00 1.07 2.17 2.04 6.24 5.619 6.992 6.994 7.013 7.015 7.029 7.030 7.048 7.260 7.407 7.427 7.447 7.552 7.555 7.570 7.572 7.589 7.593 7.606 7.609 7.624 7.626 7.629 7.644 7.647 7.951 7.954 7.973 8.205 8.207 8.224 8.226 1.680 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 21

169.48 157.10 160.59 150.63 105.40 111.11 116.40 121.11 121.94 127.18 128.23 131.78 135.03 135.33 141.88 76.85 77.16 77.48 21.26 25.78 1.05 1.05 0.95 2.11 1.05 1.08 2.15 3.00 6.07 6.867 6.869 6.887 6.889 7.031 7.072 7.085 7.089 7.102 7.106 7.260 7.388 7.407 7.463 7.483 7.503 7.569 7.590 8.197 8.237 2.302 1.729 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 22

157.09 160.65 101.32 105.31 106.35 108.47 110.93 115.99 120.88 122.41 125.12 131.81 132.59 135.24 142.14 147.94 148.31 76.84 77.16 77.48 25.77 1.02 1.01 1.02 2.10 1.01 1.03 1.04 6.20 5.973 6.780 6.800 6.836 6.856 6.978 6.997 7.019 7.145 7.260 7.369 7.388 7.441 7.461 7.480 8.083 8.123 1.724 11 10 9 8 7 6 5 4 3 2 1 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 23

157.07 159.86 160.70 105.28 110.86 114.24 115.82 120.82 124.62 128.59 130.03 132.51 135.22 142.38 76.84 77.16 77.48 55.44 25.76 1.01 1.06 2.12 1.15 1.06 1.13 2.12 3.00 6.08 6.832 6.835 6.851 6.854 6.890 6.895 6.907 6.912 7.036 7.077 7.260 7.397 7.415 7.417 7.446 7.466 7.485 7.512 7.516 7.529 7.533 8.134 8.175 3.828 1.727 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 24

157.12 159.54 160.71 105.29 110.91 114.86 115.78 120.82 124.50 128.61 129.88 132.65 135.21 142.50 76.84 77.16 77.48 67.92 31.45 25.81 19.38 13.99 0.94 4.04 0.98 1.98 0.98 1.97 1.94 5.92 2.05 3.00 6.828 6.832 6.848 6.851 6.882 6.886 6.899 6.904 7.035 7.075 7.260 7.397 7.399 7.417 7.419 7.444 7.464 7.484 7.490 7.497 7.502 7.514 7.519 8.132 8.172 3.972 3.988 4.004 1.456 1.474 1.479 1.492 1.497 1.511 1.516 1.530 1.549 1.593 1.728 1.742 1.759 1.774 1.778 1.789 1.796 1.813 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 25

157.10 159.53 160.69 105.27 110.89 114.81 114.85 114.88 115.77 120.80 124.47 128.56 128.59 128.63 129.85 132.64 135.19 142.48 76.84 77.16 77.48 68.23 14.22 22.78 25.79 26.17 29.37 29.39 29.49 31.94 1.04 1.02 2.08 1.03 2.21 2.05 2.04 6.07 2.24 10.78 3.11 0.876 0.894 0.903 0.911 1.293 1.297 1.305 1.320 1.324 1.329 1.338 1.349 1.369 1.375 1.442 1.462 1.480 1.614 1.727 1.752 1.769 1.789 1.806 3.959 3.975 3.992 6.827 6.830 6.847 6.850 6.880 6.885 6.897 6.902 7.034 7.075 7.260 7.396 7.398 7.415 7.418 7.442 7.462 7.481 7.490 7.497 7.501 7.514 7.519 8.135 8.175 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 26

157.17 160.61 105.56 111.24 116.95 121.26 126.24 128.94 130.20 130.72 131.88 132.97 135.47 137.41 141.24 76.84 77.16 77.48 25.79 1.00 3.07 1.01 0.95 2.02 5.93 6.900 6.903 6.915 6.921 6.923 6.955 7.260 7.356 7.375 7.382 7.386 7.403 7.407 7.412 7.432 7.480 7.480 7.500 7.520 7.520 7.617 7.622 8.203 8.243 1.735 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 27

76.84 77.16 77.48 103.86 104.11 104.37 105.50 111.20 111.77 111.81 111.99 112.02 116.72 121.33 121.52 121.64 121.68 123.63 128.37 128.42 128.47 128.52 128.59 135.45 141.72 157.13 159.32 160.61 161.46 161.58 161.83 161.94 163.95 164.07 25.79 1.00 1.01 1.02 1.03 1.03 1.03 6.00 6.791 6.798 6.814 6.819 6.823 6.840 6.846 6.876 6.882 6.890 6.902 6.910 7.162 7.203 7.260 7.399 7.418 7.479 7.500 7.519 7.680 7.702 7.718 7.739 8.201 8.242 1.733 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 28

105.30 110.92 115.23 115.86 120.85 124.82 127.61 128.13 128.63 128.73 130.34 132.49 135.22 136.98 142.40 157.10 159.09 160.68 70.18 76.84 77.16 77.48 25.79 1.05 1.05 2.08 1.11 7.39 2.20 6.24 5.099 6.840 6.842 6.860 6.862 6.972 6.994 7.037 7.078 7.260 7.316 7.333 7.339 7.351 7.378 7.397 7.417 7.439 7.451 7.456 7.470 7.490 7.516 7.537 8.146 8.187 1.734 11 10 9 8 7 6 5 4 3 2 1 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 29

153.50 157.11 160.73 126.46 132.76 133.00 135.33 138.56 141.93 121.02 116.24 104.34 105.40 111.01 76.84 77.16 77.48 61.08 56.25 25.77 1.03 2.01 1.07 1.26 1.09 1.06 3.00 6.19 6.56 6.798 6.856 6.859 6.876 6.879 6.981 7.022 7.260 7.381 7.400 7.457 7.477 7.497 8.136 8.176 3.862 3.906 1.725 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm 30

174.32 158.50 161.81 116.42 116.47 119.07 126.96 129.03 129.06 130.70 131.68 133.97 141.99 48.49 48.66 48.83 49.00 49.17 49.34 49.51 1.00 1.80 1.45 1.23 1.08 3.24 7.592 7.624 7.297 7.312 7.341 7.356 7.120 7.136 6.760 6.775 6.788 6.805 6.851 6.882 6.760 6.775 6.788 6.805 6.851 6.882 7.120 7.136 7.297 7.312 7.341 7.356 7.592 7.624 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 ppm 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 31

170.19 156.58 147.13 147.87 101.16 105.49 108.53 114.90 116.18 119.77 121.39 125.07 129.93 130.71 131.53 136.61 38.89 39.10 39.31 39.52 39.73 39.94 40.15 1.08 1.11 3.42 1.18 2.21 6.035 6.777 6.797 6.909 6.929 6.971 6.974 6.991 6.995 7.008 7.048 7.088 7.091 7.131 7.151 7.202 7.223 7.242 7.262 2.494 2.499 2.503 13 12 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 32

159.16 114.24 114.78 116.12 123.95 127.76 129.49 130.04 130.65 136.37 38.90 39.10 39.31 39.52 39.73 39.94 40.15 55.13 0.96 2.30 4.38 2.12 3.00 6.821 6.837 6.946 6.965 7.103 7.181 7.199 7.230 7.249 7.268 7.434 7.453 3.770 12 11 10 9 8 7 6 5 4 3 2 1 ppm 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm 33

175.61 159.30 163.35 114.84 114.94 116.92 119.87 127.20 128.24 130.07 131.50 135.53 142.90 76.84 77.16 77.48 67.98 31.44 19.38 13.99 1.22 2.86 0.99 2.82 0.88 2.09 2.18 3.23 6.819 6.859 6.885 6.906 6.920 6.941 7.109 7.128 7.259 7.406 7.430 7.452 7.680 7.720 3.970 3.986 4.002 0.968 0.987 1.005 1.474 1.493 1.511 1.530 1.745 1.761 1.781 1.799 11 10 9 8 7 6 5 4 3 2 1 ppm 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 34

175.64 159.33 163.43 109.64 114.96 116.95 119.91 127.17 128.25 130.05 131.57 135.62 142.94 68.31 76.85 77.16 77.48 22.81 26.19 29.40 29.52 31.97 14.24 2.88 0.95 4.10 1.02 2.11 11.24 3.22 6.825 6.865 6.891 6.912 6.926 6.947 7.115 7.134 7.260 7.415 7.437 7.458 7.679 7.719 3.963 3.980 3.996 0.914 1.265 1.297 1.324 1.326 1.340 1.351 1.427 1.444 1.463 1.478 1.758 1.775 1.794 1.812 11 10 9 8 7 6 5 4 3 2 1 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 35

169.87 156.32 115.74 116.77 126.25 127.86 128.22 128.91 129.90 130.89 131.03 131.53 135.86 137.83 1.27 1.00 2.08 2.16 1.05 1.00 1.08 6.856 6.875 7.088 7.128 7.181 7.199 7.283 7.302 7.321 7.349 7.390 7.495 7.515 7.616 7.636 7.756 2.500 12 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 36

103.99 104.25 104.51 111.91 111.94 112.15 115.87 116.57 121.22 121.30 121.67 129.08 129.13 129.17 129.22 129.58 130.91 136.23 158.41 158.53 160.38 160.90 161.02 162.72 162.85 38.89 39.10 39.31 39.52 39.73 39.94 40.15 1.00 1.03 2.12 0.88 1.02 6.897 6.915 7.065 7.094 7.111 7.132 7.149 7.182 7.201 7.241 7.246 7.263 7.268 7.280 7.292 7.298 7.463 7.478 7.678 7.694 2.496 2.500 2.504 12 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 37

159.88 162.02 116.06 116.58 119.11 128.23 128.50 128.82 128.90 129.44 131.01 132.09 133.81 138.55 141.97 70.99 48.49 48.66 48.83 48.85 49.00 49.02 49.17 49.19 49.34 49.51 1.06 1.25 2.13 1.27 1.96 2.09 4.12 1.09 6.783 6.799 6.834 6.866 6.918 6.935 7.098 7.113 7.273 7.282 7.289 7.296 7.304 7.329 7.345 7.359 7.401 7.417 7.713 7.745 4.845 5.045 3.293 3.297 3.300 3.303 3.306-0.012 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 38

170.09 153.09 156.46 115.02 116.38 119.89 126.29 130.37 130.73 132.78 136.54 137.58 103.91 55.86 60.11 38.89 39.10 39.31 39.52 39.73 39.94 40.15 3.27 1.15 1.11 2.33 3.00 5.96 6.822 7.018 7.058 7.142 7.162 7.239 7.259 7.279 7.293 7.334 3.676 3.812 2.500 12 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 39

169.80 157.34 160.46 146.95 148.99 135.38 139.45 121.40 125.56 129.74 112.24 115.72 105.27 76.84 77.16 77.48 36.80 36.99 21.27 25.78 0.99 1.05 1.73 1.03 1.71 2.60 6.38 6.812 6.814 6.832 6.835 6.858 6.877 6.971 6.992 7.245 7.260 7.266 7.364 7.384 7.404 2.281 2.867 2.886 2.892 2.907 3.346 3.361 3.367 3.386 1.695 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 40

157.31 160.40 145.78 147.03 147.60 135.31 135.77 100.83 105.23 108.18 109.32 112.24 115.65 121.53 125.57 76.84 77.16 77.48 37.12 37.32 25.78 1.02 2.04 0.99 1.03 1.02 1.93 2.01 5.99 5.906 6.660 6.664 6.680 6.684 6.700 6.720 6.770 6.773 6.807 6.810 6.828 6.830 6.850 6.852 6.869 6.871 7.260 7.360 7.380 7.399 2.795 2.814 2.820 2.835 3.313 3.327 3.333 3.337 3.353 1.699 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 41

157.30 157.99 160.41 147.28 125.59 129.72 134.00 135.26 112.30 113.85 115.55 105.19 76.84 77.16 77.48 55.38 36.73 37.00 25.78 2.96 1.14 2.05 1.03 3.00 2.05 2.08 6.08 6.803 6.824 6.848 6.867 7.145 7.167 7.260 7.352 7.372 7.391 2.825 2.844 2.849 2.865 3.339 3.354 3.359 3.379 3.780 1.692 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 42

157.30 157.57 160.41 147.35 125.60 129.67 133.81 135.25 112.31 114.50 115.54 105.19 76.84 77.16 77.48 67.85 31.56 36.75 37.02 25.79 19.41 13.99 2.99 1.12 1.98 1.02 1.91 1.97 2.22 6.26 2.20 3.14 6.793 6.798 6.814 6.848 6.867 7.128 7.149 7.260 7.350 7.370 7.389 0.952 0.970 0.989 1.439 1.457 1.476 1.494 1.513 1.532 1.692 1.715 1.732 1.752 1.769 1.786 2.816 2.835 2.856 3.335 3.356 3.375 3.916 3.932 3.948 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 43

157.29 157.55 160.42 147.33 125.59 129.67 133.78 135.26 112.29 114.48 115.53 105.19 76.84 77.16 77.48 68.16 14.23 22.79 25.78 26.22 29.39 29.49 29.52 31.96 36.75 37.03 3.08 1.01 2.02 1.07 2.03 6.24 2.21 10.77 3.47 0.870 0.877 0.888 0.898 0.905 1.259 1.277 1.287 1.294 1.301 1.313 1.317 1.327 1.337 1.348 1.357 1.362 1.692 1.742 1.762 1.780 2.815 2.835 2.840 2.855 3.334 3.349 3.354 3.374 3.904 3.920 3.937 6.792 6.798 6.801 6.808 6.813 6.819 6.822 6.847 6.849 6.866 6.868 7.128 7.133 7.145 7.149 7.260 7.350 7.370 7.390 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 44

157.40 160.44 112.16 116.00 125.53 128.36 129.95 130.32 130.74 132.19 135.49 142.12 146.22 105.36 76.84 77.16 77.48 36.56 36.64 25.75 1.95 0.95 1.85 0.99 1.99 6.11 6.832 6.851 7.080 7.085 7.101 7.106 7.259 7.313 7.327 7.333 7.375 7.395 7.415 2.828 2.847 2.853 2.868 3.309 3.323 3.329 3.349 1.697 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 45

76.84 77.16 77.48 103.26 103.51 103.77 105.31 110.93 110.97 111.14 111.17 112.22 115.88 124.26 124.38 124.42 125.64 131.63 131.70 131.72 131.79 135.33 146.39 157.35 159.73 159.85 160.26 160.45 162.30 162.70 162.82 35.30 25.77 29.65 0.99 1.00 4.02 5.90 6.697 6.704 6.721 6.728 6.744 6.751 6.765 6.771 6.791 6.811 6.833 7.167 7.183 7.188 7.204 7.226 7.337 7.357 7.377 2.898 2.917 2.937 3.325 3.345 3.363 1.701 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 46

154.17 157.30 160.99 147.36 125.59 129.81 133.71 135.47 112.13 115.34 105.37 76.91 77.16 77.41 36.78 37.01 25.72 1.94 1.03 1.02 1.96 0.97 0.97 6.11 5.701 6.769 6.786 6.813 6.829 6.880 6.896 7.092 7.109 7.260 7.375 7.391 7.406 2.809 2.825 2.841 3.339 3.351 3.355 3.371 1.692 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 47

170.49 155.39 156.32 141.02 129.00 130.74 131.79 113.85 115.03 120.26 36.47 38.89 39.10 39.31 39.52 39.73 39.94 40.15 1.38 0.83 3.96 1.88 1.00 1.97 9.123 6.657 6.677 6.697 6.721 6.741 6.976 6.995 7.138 7.157 7.176 2.687 2.707 2.819 2.839 12 11 10 9 8 7 6 5 4 3 2 1 ppm 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 48

170.33 156.62 140.87 145.33 147.20 128.79 130.86 135.60 108.11 108.69 114.07 120.36 121.00 100.65 36.51 36.99 39.02 39.19 39.36 39.52 39.69 39.86 40.02 1.00 1.14 3.31 1.20 2.06 2.15 5.952 6.633 6.649 6.689 6.704 6.743 6.759 6.777 6.790 6.806 7.145 7.161 7.176 2.719 2.729 2.861 11 10 9 8 7 6 5 4 3 2 1 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 49

175.64 163.76 157.96 146.51 129.50 134.07 135.63 123.15 110.79 113.96 116.38 76.91 77.16 77.41 55.42 37.50 38.90 1.12 2.18 1.01 0.98 2.97 1.96 6.731 6.750 6.825 6.846 6.898 6.918 7.100 7.121 7.260 7.340 7.359 7.379 2.851 2.870 2.890 3.256 3.277 3.296 3.794 11 10 9 8 7 6 5 4 3 2 1 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 50

175.54 163.42 157.52 146.45 129.42 133.89 135.34 114.36 114.56 116.23 123.11 76.91 77.16 77.41 67.88 37.46 38.81 31.51 19.39 14.01 1.13 1.92 0.90 1.83 1.02 1.75 1.86 2.31 2.31 3.33 6.702 6.717 6.795 6.811 6.865 6.881 7.063 7.079 7.260 7.293 7.303 7.317 1.457 1.472 1.487 1.502 1.674 1.689 1.704 1.718 1.732 1.747 1.761 1.775 2.815 2.830 2.845 3.226 3.242 3.257 3.909 3.922 3.935 12 11 10 9 8 7 6 5 4 3 2 1 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 51

175.43 163.75 157.56 146.50 129.43 133.83 135.60 123.14 110.69 114.57 116.34 76.91 77.16 77.42 68.22 14.26 22.81 26.21 29.40 29.47 29.53 31.97 37.52 38.94 0.98 2.02 1.10 2.01 1.01 2.01 11.32 3.22 6.726 6.740 6.814 6.831 6.890 6.907 7.082 7.098 7.260 7.337 7.353 7.369 0.875 0.888 1.285 1.296 1.311 1.322 1.426 1.440 1.748 1.762 1.776 2.838 2.853 2.869 3.245 3.262 3.277 3.912 3.925 3.938 12 11 10 9 8 7 6 5 4 3 2 1 ppm 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 52