Characteristic Fluctuations in Glycosidically Bound Volatiles during Tea Processing and

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Characteristic Fluctuations in Glycosidically Bound Volatiles during Tea Processing and Identification of Their Unstable Derivatives Jilai Cui a,b, Tsuyoshi Katsuno c, Kojiro Totsuka d, Toshiyuki Ohnishi d,e, Hiroyuki Takemoto e, Nobuyuki Mase e,f, Mitsuo Toda f, Tetsuo Narumi f, Kohei Sato f, Testuaki Matsuo f, Kenta Mizutani f, Ziyin Yang g, Naoharu Watanabe b,f,, Huarong Tong a, a College of Food Science, Southwest University, No.2 Tiansheng Road, BeiBei District, Chongqing, 400715, P. R. China b Graduate School of Science and Technology, Shizuoka University, 3-5-1 Johoku, Naka-ku, Hamamatsu 432-8561, Japan c Shizuoka Prefectural Research Institute of Agriculture and Forestry, Tea Research Center, 1709-11 Kurasawa, Kikugawa, Shizuoka 439-0002, Japan d Graduate School of Agriculture, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan e Research Institute of Green Science and Technology, 836 Ohya, Suguga-ku, Shizuoka 422-8529, Japan f Graduate School of Engineering, Shizuoka University, 3-5-1 Johoku, Naka-ku, Hamamatsu 432-8561, Japan g Key Laboratory of Plant Resource Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Xingke Road 723, Tianhe District, Guangzhou 510650, China Corresponding authors: Tel.: +81 (0)53 478 1160 (N.Watanabe); fax: +81 (0)53 478 1160 (N.Watanabe); Tel.: +86 151 2318 0688 (H. Tong); fax: +86 023 6825 1947 (H. Tong) E-mail addresses: watanabe.naoharu@shizuoka.ac.jp (N.Watanabe); huart@swu.edu.cn (H. Tong) 1

Authentic compounds and their corresponding numbers in the Supplementary information benzyl β-d-glucopyranoside (1), benzyl β-primeveroside (2), 2-phenylethyl β-d-glucopyranoside (3), 2-phenylethyl β-primeveroside (4), (Z)-3-hexenyl β-d-glucopyranoside(5), (Z)-3-hexenyl β-primeveroside (6), geranyl β-d-glucopyranoside (7), geranyl β-primeveroside (8), linalyl β-d-glucopyranoside (9), linalyl β-primeveroside (10), 4-Isopropylbenzyl β-d-glucopyranoside (11), Phenyl β-d-glucopyranoside (12), benzyl 6 -O-malonyl-β-D-glucopyranoside (13), 2-phenylethenyl 6 -O-malonyl-β-D-glucopyranoside (14), (Z)-3-hexenyl 6 -O-malonyl-β-D-glucopyranoside (15), phenyl 6 -O-malonyl-β-D-glucopyranoside (16) 2

Supplemental data Benzyl 6 -O-malonyl-β-D-glucopyranoside (13) δ C (ppm, 125 MHz, d 6 -DMSO) 41.52 (C2 ), 64.44 (C6 ), 69.61 (C1), 70.06 (C4 ), 73.33 (2 ), 73.57 (C5 ), 76.41 (C3 ), 102.06 (C1 ), 127.37 (C5), 127.74 (C3, C7), 128.10 (C4, C6), 137.85 (C2), 166.88 (C1 ), 167.91 (C3 ); δ H (ppm, 500 MHz, d 6 -DMSO) 3.06 (1H, dd, J =8.5. 8.0 Hz, H2 ), 3.10 (1H, dd, J =8.9, 8.5 Hz, H4 ), 3.17 (1H, dd, J =8.9, 8.5 Hz, H3 ), 3.36 (1H, ddd, J =8.6, 6.0, 2.0 Hz, H5 ), 3.42 (2H, brs, H2 ), 4.15 (1H, dd, J =11.0, 6.0 Hz, H6 a), 4.25 (1H, d, J =8.0 Hz, H1 ), 4.35 (1H, dd, J =11.0, 2.0 Hz, H6 b), 7.28 (1H, m, H5), 7.36 (5H, m, H3, H4, H6, H7). Significant HMBC cross peaks were detected from H1 to C1, H6 to C1, and H2 to C1. HRMS (ESI, positive) m/z 379.0994 [M+Na] + (calcd. 379.09995). 2-Phenylethyl 6 -O-malonyl-β-D-glucopyranoside (14) δ C (ppm, 125 MHz, d 6 -DMSO) 35.66 (C2), 42.52 (C2 ), 64.43 (C6 ), 69.91 (C1), 69.96 (C4 ), 73.27 (2 ), 73.55 (C5 ), 76.45 (C3 ), 102.90 (C1 ), 126.03 (C6), 128.21 (C4, C8), 128.89 (C5, C7), 137.74 (C3), 166.93 (C1 ), 167.91 (C3 ); δ H (ppm, 500 MHz, d 6 -DMSO) 2.86 (2H, ddd, J = 11.0, 6.2, 2.0 Hz, H2), 2.98 (1H, dd, J =8.0. 8.0 Hz, H2 ), 3.08 (1H, dd, J =8.8, 8.4 Hz, H4 ), 3.17 (1H, dd, J =8.4, 8.0 Hz, H3 ), 3.38 (2H, brs, H2 ), 3.39 (1H, m, overlapped with water, H5 ), 3.69 (1H, ddd, J =10.5, 6.0, 2.0 Hz, H1a), 3.82 (1H, ddd, J =10.5, 6.0, 6.0 Hz, H1b), 4.11 (1H, dd, J =10.5, 6.0 Hz, H6 a), 4.23 (1H, d, J =8.0 Hz, H1 ), 4.34 (1H, dd, J =10.5, 2.0 Hz, H6 b), 7.20 (1H, m, H6), 7.27 (5H, m, H4, H5, H7, H8). Significant HMBC cross peaks were detected from H1 to C1, H6 to C1, and H2 to C1. HRMS (ESI, positive) m/z 393.1152 [M+Na] + (calcd. 393.11560). (Z)-3-Hexenyl 6 -O-malonyl-β-D-glucopyranoside (15) δ C (ppm, 125 MHz, CD 3 OD) 14.61 (C6), 21.51 (C5), 28.77 (C2), 42.48 (C2 ), 65.42 (C6 ), 70.50 (C1), 71.55 (C4 ), 74.99 (C2 ), 75.14 (C5 ), 77.95 (C3 ), 104.32 (C1 ), 125.86 (C3 ), 134.51 (C4 ), 137.74 (C3), 169.02 (C1 ), 170.33 (C3 ); δ H (ppm, 500 MHz, CD 3 OD) 0.97 (3H, t, J = 7.8 Hz, H6), 2.07 (2H, dq, J =7.8, 7.5 Hz, H5), 2.37 (2H, 3

dt, J =7.2,6.3 Hz, H2), 3.18 (1H, dd, J =8.5, 8.0 Hz, H2 ), 3.32 (1H, dd, J =8.5, 8.4 Hz H4 ), 3.36 (1H, dd, J =8.5, 8.4 Hz H3 ), 3.47 (1H, m, H5 ), 3.53 (1H, dt, J =9.6, 7.2 Hz, H1a), 3.80 (1H, dt, J =9.6, 7.2 Hz, H1b), 4.27 (1H, dd, J =11.0, 7.0 Hz, H6 a), 4.45 (1H, dd, J =11.0, 2.0 Hz, H6 b), 5.39 (1H, m, H3), 5.41 (1H, m, H4). H2 were exchanged with deuterium atoms of CD 3 OD. Significant HMBC cross peaks were detected from H1 to C1 and H6 to C1. HRMS (ESI, positive) m/z 371.1314 [M+Na] + (calcd. 371.13125). Phenyl 6 -O-malonyl-β-D-glucopyranoside (16) δ H (ppm, 300 MHz, d 4 - CH 3 OH) 3.38 (3H, m, overlapped with solvent, H2, H3, H4 ), 3.67 (1H, m, H5 ), 4.26 (1H, dd, J =10.5, 7.2 Hz, H6 a), 4.54 (1H, d, J =11.7 Hz, H6 b), 4.88 (1H, d, overlapped with water, H1 ), 7.00 (1H, t, J =7.2 Hz, H3), 7.07 (2H, d, J =7.8 Hz, H1, H5), 7.29 (2H, t, J =7.2 Hz, H2, H4); HRMS (ESI, positive) m/z 365.0856 [M+Na] + (calcd. 365.08541). 4

Figure S1 5

Figure S1. Total ion chromatography and SIM of standard compounds (a), of withered tea leaves (b) and calibration curves for each GBV (c). In (a) and (b), Y axis denotes peak intensity. 1. Total ion chromatography. 2. m/z 315, Rt 9.5 min, 1. 3. m/z 447, Rt 11.8 min, 2. 4. m/z 329, Rt 18.6, 3. 5. m/z 307, Rt 20.8 min, 5. 6. m/z 461, Rt 23 min, 4. 7. m/z 439 Rt 27.1 min, 6. 8. m/z 357, Rt 48.3 min, 11 (IS). 9. m/z 493, Rt 52.4 min, 10, Rt 54.6 min, 8. 10. m/z 361, Rt 55.6 min, 9, Rt 59.1 min, 7. In (c), the Y axis denotes ion intensity of each authentic glycoside divided by that of internal standard. The X axis denotes concentration of the authentic compound (µm). 6

Figure S2 7

Figure S2. Identification of malonyl esters of GBVs in tea leaves based on the LC-HRMS analysis. Traces at m/z 371.1263-371.1363 for [M+Na] + of 15, (a) synthetic compound; (b) in fresh leaves; (c) in indoor withered tea leaves; m/z 379.0985-379.1005 for [M+Na] + of 13, (d) synthetic compound; (e) in fresh leaves; (f) in indoor withered tea leaves; trace m/z 393.1142-393.1162 for [M+Na] + of 14, (g) synthetic compound; (h) in fresh leaves; (i) in withered tea leaves. The Y axis denotes the peak area of each compound. 8

Figure S3 9

10

11

Figure S3. Mass spectra of standard reference compounds. Figures a-k are the mass spectra of GBVs (a-j) and internal standard (k) obtained by LC-HRMS. Figures l-o are MS, MS 2 and MS 3 of 15, 13, 14 and 16, respectively. The corresponding precursor ions are indicated with a vertical arrow. 12

Figure S4 Figure S4. Conversion of 16 to 12 after heating at 230 o C for 2 min. Compounds 12 and 16 were detected at 5.9 min and 20.1 min, respectively. HPLC conditions: Shiseido CAPCELL PAK C18 UG120; mobile phases were (A) 0.1% (v/v) formic acid in water and (B) 0.1% (v/v) formic acid and acetonitrile. Solvent B was maintained at 9%. Detection wavelength was 254 nm and flow rate was 1.0 ml/min. 13

Figure S5. Figure S5. LC analyses of methanol extract from the tea powders heated at 230 o C for 4 min in the presence of phenol and glucose. Retention time of phenol and 16 were 25.3 and 18.0 min, respectively, under the conditions shown below. Glucose cannot be detected under 254 nm. HPLC conditions: Shiseido CAPCELL PAK C18 UG120; mobile phases were (A) 0.1% (v/v) formic acid in water and (B) 0.1% (v/v) formic acid in acetonitrile. Solvent B was maintained 3% for 20 min and then increased to 70% in 10 min and kept for 5 min. Detection wavelength was 254 nm and flow rate was 1.0 ml min -1. Phenyl glucoside was not detected in the reaction mixture. 14

Table S1. Content of GBVs in fresh tea leaves (µmol / 100 g DW) Yabukita Koshun Tsuyuhikari Qingxindamao Okuhikari Sayamakaori Yamanoibuki 1 32.7±9.98 32.1±1.01 42.6±1.68 69.87±5.09 49.97±2.84 23.78±0.85 50.37±8.08 3 1.51±0.5 1.09±0.00 3.59±0.38 3.50±0.02 2.36±1.61 3.96±0.25 9.02±0.77 5 13.02±1.82 9.65±0.60 3.62±0.19 2.02±0.44 6.17±0.05 6.58±0.29 7.00±0.05 7 0.2±0.06 0.12±0.00 0.14±0.03 1.77±0.11 n.d. 0.37±0.03 0.2±0.07 9 n.d. 0.03±0.02 0.01±0.03 0.14±0.00 n.d. n.d. n.d. Glucosides 47.42±10.41 42.98±1.60 49.97±1.78 77.30±5.41 58.49±4.45 34.69±1.37 66.59±8.73 2 33.39±1.98 21.15±0.82 20.9±0.58 38.95±3.85 20.17±0.65 19.00±0.95 14.09±0.72 4 14.36±1.66 9.50±0.25 10.31±1.73 27.60±1.65 3.45±0.14 23.10±0.41 21.2±2.38 6 9.08±0.48 10.18±0.51 2.89±0.10 5.45±0.45 2.42±0.11 6.33±0.17 3.94±0.19 8 44.87±5.54 28.09±2.16 41.09±1.39 145.38±4.20 16.32±0.14 29.49±0.65 14.43±0.85 10 17.39±1.35 14.24±0.29 26.52±0.94 16.39±0.54 24.88±0.95 5.39±0.28 9.18±0.44 Primeverosides 119.09±10.37 83.16±1.05 101.71±2.24 233.77±10.68 67.24±0.85 83.30±0.93 62.84±4.24 Total 166.51±18.70 126.14±1.46 151.67±3.89 311.07±16.08 125.73±5.22 117.98±0.47 129.43±9.16 The results are expressed as mean±sd, n=3. N.d, not detected. 15

Table S2. Changes in GBV contents during black tea manufacturing process (µmol / 100 g DW) Fresh Withered Rolled 1h 2h 3h 4h 1 54.42±4.85 65.08±18.27 53.64±1.37 50.42±6.19 57.85±5.32 49.88±4.08 68.65±13.71 3 50.10±2.16 57.65±6.43 47.82±1.00 37.71±5.45 48.14±10.01 39.85±1.57 51.29±8.84 5 17.55±1.02 17.67±3.34 8.21±0.20 5.48±1.23 7.76±2.07 5.34±0.18 7.65±2.52 7 9.66±0.47 9.68±1.06 8.24±0.46 7.91±0.31 9.03±0.92 8.14±0.32 10.16±1.31 9 0.40±0.03 0.33±0.05 0.16±0.01 0.16±0.01 0.22±0.05 0.16±0.02 0.24±0.05 Glucoside 132.14±8.37 150.41±27.91 118.07±0.96 101.68±12.49 122.99±17.24 103.38±3.76 137.99±26.33 2 38.61±2.71 50.28±8.70 n.d. n.d. n.d. n.d. n.d. 4 137.94±4.52 157.90±34.47 n.d. n.d. n.d. n.d. n.d. 6 7.27±0.29 11.94±2.03 0.56±0.04 0.59±0.08 0.62±0.04 0.56±0.03 0.68±0.01 8 135.08±2.53 168.96±35.50 n.d. n.d. n.d. n.d. n.d. 10 n.d. 2.63±2.11 n.d. n.d. n.d. n.d. n.d. Primeverosides 318.90±9.75 391.71±81.96 2.58±0.16 0.59±0.08 0.62±0.04 0.56±0.03 0.68±0.01 Total 451.03±18.04 542.12±109.72 120.65±1.09 102.27±12.49 123.61±17.22 103.94±3.78 138.68±26.32 The results are expressed as mean±sd, n=3. N.d, not detected. 16

Table S3. Changes in GBV content during oolong tea manufacturing process (µmol / 100 g DW) Fresh Solar Indoor 1st turnover 2nd turnover 3rd turnover fixed made tea 1 50.20±3.65 45.62±3.04 81.40±1.49 61.62±7.08 58.13±5.15 58.85±1.71 130.49±11.53 98.97±0.96 3 21.28±1.46 18.01±1.09 57.89±1.59 29.56±5.40 25.26±5.36 32.61±1.17 93.50±8.68 72.39±1.26 5 55.12±2.47 64.27±1.05 202.03±8.07 170.11±21.04 198.16±18.36 239.27±4.70 317.99±21.83 272.64±4.67 7 0.86±0.15 0.88±0.18 1.62±0.22 0.58±0.17 0.49±0.04 0.66±0.08 1.53±0.03 1.05±0.04 9 n.d. n.d. n.d. n.d. n.d. n.d. 0.28±0.14 0.03±0.07 Glucoside 127.46±5.69 128.77±5.19 342.94±9.55 261.87±33.63 282.04±28.68 331.39±7.13 543.78±42.11 445.06±3.55 2 5.03±1.03 3.70±0.37 4.33±0.29 6.79±0.75 6.49±0.33 6.09±0.77 18.76±3.44 9.05±0.22 4 4.31±0.72 4.30±0.15 4.83±0.13 6.35±0.63 6.14±0.08 6.52±0.93 44.83±2.37 31.58±1.59 6 0.05±0.03 0.01±0.06 1.02±0.15 0.53±0.16 0.91±0.12 1.01±0.17 26.05±0.68 17.18±0.92 8 6.18±0.79 6.18±1.18 4.33±0.31 5.53±0.70 5.39±0.28 4.39±0.17 8.45±1.41 6.24±0.24 10 n.d. n.d. n.d. n.d. n.d. n.d. 23.37±1.44 12.90±1.47 Premiveroside 15.57±2.44 14.18±1.70 14.51±0.64 19.20±2.22 18.93±0.54 18.01±1.74 121.47±7.96 76.95±2.83 Total 143.03±8.11 142.95±6.63 357.45±9.86 281.08±35.85 300.97±28.63 349.40±8.81 665.24±50.08 522.00±4.64 The results are expressed as mean±sd, n=3. N.d, not detected. 17