A new ent-kaurane diterpene from Euphorbia stracheyi Boiss

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SUPPLEMENTARY MATERIAL A new ent-kaurane diterpene from Euphorbia stracheyi Boiss Tie Liu a, Qian Liang a,b, Na-Na Xiong a, Lin-Feng Dai a, Jun-Ming Wang a,b, Xiao-Hui Ji c, Wen-Hui Xu a, * a Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 65224, PR China b Department of Medicinal Plant, School of Forestry, Southwest Forestry University, Kunming 65224, PR China c Department of Applied Chemistry, School of Chemistry and Environment Science, Shaanxi University of Technology, Hanzhong 723, PR China Corresponding author: To whom correspondence should be addressed: Tel: 86-87-6386242;Fax: 86-87-6386345; E-mail address: Wenhuix@ hotmail.com Abstract: The chemical investigation of whole plants Euphorbia stracheyi Boiss from China led to the isolation of one new ent-kaurane diterpene, ent-kaurane-6β,7,9-triol-3-one (), along with three known ent-kaurane diterpenoids (2 4) as ent-kaurane-3α,6β,7-triol (2), ent-6s,7-dihydroxy-kaurane-3-one (3), and ent-3s,6s,7-trihydroxy-kaurane-2-one (4). Their structures were elucidated by extensive spectroscopic analyses including D, 2D NMR, HR-ESI-MS, and by comparison with the literature. Compound 2 was a new natural product and firstly isolated from nature, while compounds (3 4) were isolated from E. stracheyi for the first time. All isolated compounds ( 4) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-772, HL-6, MCF-7, and SW-48).

Contents of supplementary data Figure S. H -NMR spectrum of compound (5MHz, Pyridine-d 5 ) Figure S2. 3 C-NMR spectrum of compound (25MHz, Pyridine-d 5 ) Figure S3. DEPT-9,35 NMR spectrum of compound (Pyridine-d 5 ) Figure S4. H - H COSY spectrum of compound (Pyridine-d 5 ) Figure S5. HMQC NMR spectrum of compound (Pyridine-d 5 ) Figure S6. HMBC NMR spectrum of compound (Pyridine-d 5 ) Figure S7. ROESY NMR spectrum of compound (Pyridine-d 5 ) Figure S8. ESI-MS spectrum of compound Figure S9. ESI-HR-MS spectrum of compound Figure S. H -NMR spectrum of compound 2 (5MHz, Pyridine-d 5 ) Figure S. 3 C-NMR spectrum of compound 2 (25MHz, Pyridine-d 5 ) Figure S2. H -NMR spectrum of compound 3 (5MHz, Methanol-d4) Figure S3. 3 C-NMR spectrum of compound 3 (25MHz, Methanol-d4) Figure S4. H -NMR spectrum of compound 4 (5MHz, Pyridine-d 5 ) Figure S5. 3 C-NMR spectrum of compound 4 (25MHz, Pyridine-d 5 ) Figure S6. Key HMBC and COSY correlations of compound Table S. 3 C NMR data for compounds -4

gs64a.2..r gs64a H 8.72 7.58 7.58 7.58 7.2 7.2 6.39 6.7 5.8 4.33 4.3 3.88 3.86 3.85 3.82 3.8 3.78 2.82 2.79 2.77 2.5 2.46 2.45 2.43 2.4 2.2 2.8 2. 2..99.98.79.76.76.73.7.6.59.58.57.57.53.44.43.4.4.37.36.34.26.24.2.6 -. 3 2 9 8 7 6 5 4 3 2.84.98 3.3....98.98.3 2.5.99.98..99 3.5.96 3.6..6 3.9.4-4 3 2 9 8 7 6 5 4 Figure S. H -NMR spectrum of compound (5MHz, Pyridine-d 5 ) 3 2

2 3 4 5 6 7 8 9 2 3 4 5 6 7 8 9 2 2 22-5 5 5 2 25 3 35 4 45 5 55 gs64a.22..r gs64a c3 8.3 2. 2.8 2.9 27.8 35.9 38.7 39.4 4.6 42. 42.5 44. 53.5 55. 56.9 57.4 65.3 7.8 8. 23.7 23.9 24. 35.7 35.9 36. 5. 5.2 5.4 25.5

4.9 57.4 56.9 gs64a.23..r gs64a c3 6E+6 4E+6 2E+6 E+ 9 8 7 6 5 4 3 2 9 8 7 7.8 gs64a.24..r gs64a c3 6 5 4 3 2 42.5 42. 4.6 38.7 35.9 27.7 2.8 2.8 9.9 8.3 2 57.4 56.9 53.5 2 65.3 22 - -2 7 6 5 5.4 5.2 5. 25.5 gs64a.22..r gs64a c3 4 3 2 9 8 7 6 5 4 3 2 65.3 57.4 56.9 55. 53.5 44. 42.5 42. 4.6 39.4 38.7 35.9 27.8 2.9 2.8 2. 8.3 8 7.8 9 8. 2 24. 23.9 23.7 2 36. 35.9 35.7 22 5 4 3 2 22 2 2 9 8 7 6 5 4 3 2 9 8 7 6 5 Figure S3. DEPT-9,35 NMR spectrum of compound (Pyridine-d5) 4 3 2

gs64a.26..2rr gs64a cosy 2 3 4 6 7 8 9 9.5 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 (ppm) of compound (Pyridine-d ) Figure S4. H -H COSYf2 spectrum 5 2..5..5 5

gs64a.27..2rr gs64a hsqc 2 3 4 5 6 7 8 2 3 4 5 6 7 8 9 2 2 22 9 8 7 6 5 4 f2 compound (ppm) Figure S5. HMQC NMR spectrum of (Pyridine-d5) 3 2 9

gs64a.28..2rr gs64a hmbc 2 3 4 5 6 7 8 2 3 4 5 6 7 8 9 2 2 22.5..5. 9.5 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. f2 (ppm) Figure S6. HMBC NMR spectrum of compound (Pyridine-d5) 2.5 2..5..5. 9

gs64a.29..2rr gs64a roesy 2 3 4 6 7 8 9.5. 9.5 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 f2 (ppm) Figure S7. ROESY NMR spectrum of compound (Pyridine-d5) 3. 2.5 2..5..5. 5

Sample Name GS-64A Position P-C3 Instrument Name Instrument User Name Inj Vol. InjPosition SampleType Sample IRM Calibration Status Success Data Filename GS-64A.d ACQ Method SIBU.m Comment Acquired Time 2/29/25 :8:5 AM

Qualitative Analysis Report Data Filename GS-64A.d Sample Name GS-64A Sample Type Sample Position P-C3 Instrument Name Instrument User Name Acq Method SIBU.m Acquired Time IRM Calibration Status Success DA Method ESI+.m Comment Column3 Sample Group Acquisition SW Version Column4 62 series TOF/65 series Q-TOF B.5. (B525.2) Column3 Info. 2/29/25 :8:5 AM User Spectra Fragmentor Voltage 35 Collision Energy Ionization Mode ESI Peak List m/z 229.24 337.2378 359.297 36.2228 375.936 462.264 695.45 696.4533 z 2 Abund 3378 373.38 2636.34 52787.57 82.98 2796.5 8737.9 7546.84 Formula C2 H32 O4 C2 H32 O4 Ion (M+Na)+ (M+Na)+ Formula Calculator Element Limits Element Min Max C 3 6 H 2 O 3 N Formula Calculator Results Formula CalculatedMass CalculatedMz Mz Diff. (mda) C2 H32 O4 336.23 359.293 359.297 -.4 Diff. (ppm) -.2 DBE 5. --- End Of Report ---

..5..5 2. 2.5 3. 3.5 4. 4.5 5. 5.5 6. 6.5 7. 7.5 8. 8.5 9. 9.5..5..5 2. -5 5 5 2 25 3 35 4 45 5 55 6 pdata/.99. 3.3 2.92.9 3.4.99.8.75.82.7. 2.3.2..7..5 2. 3.9.68.69.64 -.8.773.797.82.9.92.48.75.3.52.227.354.373.458.466.483.488.546.573.657.693.72.756.796.82.83.856.88.89.96 2. 2.45 2.224 2.47 2.48 3.44 3.468 3.63 3.798 3.825 3.88 3.97 5.8 5.8 5.33 5.82 6.474 7.24 7.58 8.733

2 3 4 5 6 7 8 9 2 3 4 5 6 7 8 9 2 2 22-2 - 2 3 4 5 6 7 8 9 2 3 4 5 6 7 8 9 2 gs54f.2..r gs54f c3 6.8 8.3 9.65 2.66 27.99 28.64 29.33 38.95 39.54 39.77 39.8 42.8 42.73 44. 53.78 55.8 57.86 7.87 78.56 8.5 23.64 23.89 24.4 35.66 35.9 36.6 49.97 5.24 5.5

..5. 9.5 9. 8.5 8. 7.5 Figure S2. 7. H 6.5 6. -NMR spectrum of compound 3 (5MHz, Methanol-d4) 5.5 5. 4.5 4. 3.5 3. 2.5 2..5..5.. 2.6.2..95 6.3.99.4 3.9 3.4 3.2 2.. 4.87 3.383 3.355 3.274 3.264 3.247 2.477 2.464 2.45 2.43 2.82 2.65 2.46 2.32 2.6.999.983.932.9.86.8.784.559.543.57.473.444.43.47.393.377.338.93.72.96.84.67.24.98 4.E+8 3.5E+8 3.E+8 2.5E+8 2.E+8.5E+8.E+8 5.E+7.E+

7.675 57.33 55.628 52.95 49.788 49.575 49.362 49.5 48.936 48.724 48.5 48.383 44.73 42.279 42.6 4.6 39.863 38.97 35.43 27.94 27.874 22.449 2.535 2.383 8.387 8.777 22.22 5.5E+8 5.E+8 4.5E+8 4.E+8 3.5E+8 3.E+8 2.5E+8 2.E+8.5E+8.E+8 5.E+7.E+ -5.E+7 22 2 2 9 8 7 6 Figure S3. 5 4 3C-NMR 3 2 9 8 7 spectrum of compound 3 (25MHz, Methanol-d4) 6 5 4 3 2

..5..5 2. 2.5 3. 3.5 4. 4.5 5. 5.5 6. 6.5 7. 7.5 8. 8.5 9. 9.5..5. -5 5 5 2 25 3 35 4 45 5 55 6 65 7 75 8 85 gs64c.2..r gs64c H 3.2 3..5 3..8.9.77 4.3.4 2.6..98. 2..98.99..98 2.94.2.95.77.88.2.9.98.24.22.296.36.324.34.348.362.379.427.43.452.464.47.478.485.489.52.59.549.574.728.756.775.78.87.864.868.888.893 2.5 2.75 2.3 2.5 2.424 2.43 2.46 2.476 2.72 2.745 3.785 3.87 3.86 3.88 4.7 5.52 7.22 7.58 8.725

2 3 4 5 6 7 8 9 2 3 4 5 6 7 8 9 2 2 22 23-5 5 5 2 25 3 35 4 45 5 55 6 gs64c.22..r gs64c c3 7.5 9. 9.6 2.7 27.6 3. 38.4 4.9 42. 44.2 45.8 53.4 54.3 54.8 56.8 7.8 79.9 83.8 23.7 23.9 24. 35.7 35.9 36. 5. 5.2 5.4 2.5

OH OH H O H OH Cosy Key HMBC Figure S6. Key HMBC and COSY correlations of compound Table S. 3 C-NMR (25 MHz) Data of Compounds 4 Position a 2 a 3 b 4 a 4.6 t 39.5 t 4.6 t 54.3 t 2 35.9 t 28.6 s 35. t 2.5 s 3 25.5 s 78.6 d 22.2 s 83.8. d 4 55. s 39.8 s 48.4 s 45.8 s 5 57.4 d 55.8 d 55.6 d 54.8 d 6 2.9 t 2.7 t 22.4 t 2.7 t 7 42.5 t 42.7 t 42.2 t 4.9 t 8 44. s 44. s 44.7 s 44.2 s 9 56.9 d 57.9 d 57.3 d 56.8 d 39.4 s 39.8 s 39.9 s 45.8 s 2. t 9.7 t 2.4 t 9.6 t 2 27.8 t 28. t 27.9 t 27.6 t 3 42. d 42.2 d 42.3 d 42. d 4 38.7 t 39. t 39. t 38.4 t 5 53.5 t 53.8 t 52.9 t 53.4 t 6 8. s 8. s 8.6 s 79.9 s 7 7.8 t 7.9 t 7.5 t 7.8 t 8 2.8 q 29.3 q 27.9 q 3. q 9 65.3 t 6.8 q 2.5 q 7.5 q 2 8.3 q 8.3 q 8.4 q 9. q a) Measured in Pyridine-d 5. b) Measured in Methanol-d 4.