# Design, Synthesis, and Cell Lines Studies of Oleanolic Acid--Hydrogen Sulfide Donor Hybrids
## 2 Materials and Methods
### General Procedure for the Synthesis of Targeted Compounds
#### 2.1.5 General Procedure for the Preparation of **14a-c**  
Compound **1** was treated in acetone at 0 \({}^{\circ}\)C with Jones reagent to form the C-3 oxidized derivative **13** in an almost quantitative yield. Then, using compound **13** as a starting material, the target products **14a-c** were obtained according to the method of preparing **2a-c** described above. _Compound 3-oxo-leanolic acid 28-[4-(4-thiocarbamoyl!)] benzoate_ **(14a)**. Yield: 45%. Yellow solid, m.p. : 144.5-145.0 \({}^{\circ}\)C: \({}^{1}\)H NMR (CDCl\({}_{3}\), 400 MHz) \(\delta\) ppm 7.66 (d, 2H, \(J\) = 8.2 Hz, Ar-H), 7.13 (d, 2H, \(J\) = 8.2 Hz, Ar-H), 5.37 (t, 1H, \(J\) = 3.2 Hz, 12-H), 2.95 (dd, 1H, \(J\) = 13.6, 2.4 Hz, 18-H), 2.53 (m, 1H, 2-Ha), 2.35 (m, 1H, 2-Hb), 1.20-2.20 (m, methylene and methine protons), 1.19 (s, 3H, 29-H), 1.07 (s, 3H, 30-H), 1.03 (s, 3H, 26-H), 1.03 (s, 3H, 23-H), 0.97 (s, 3H, 25-H), 0.93 (s, 3H, 27-H), 0.83 (s, 3H, 24-H), NH\({}_{2}\) shows no signal; \({}^{13}\)C NMR (CDCl\({}_{3}\), 100 MHz) \(\delta\) ppm 217.4, 175.5, 154.5, 145.0, 133.6, 122.8, 122.5, 109.4, 55.2, 47.4, 46.7, 46.4, 42.2, 42.1, 39.3, 39.1, 38.6, 36.7, 34.1, 32.9, 32.7, 31.8, 30.7, 27.3, 26.4, 25.6, 23.7, 23.6, 23.5, 19.5, 16.8, 15.0; HRMS (ESI) Calcd for C\({}_{37}\)H\({}_{52}\)NO\({}_{5}\)S [M + H]\({}^{+}\) 590.3662, found: 590.3667. _Compound 3-oxo-leanolic acid 28-[4-(5-thioxo-5H-1,2-dithiol-3-yl)] benzoate_ **(14b)**. Yield: 58%. Orange solid, m.p. : 197.4-198.7 \({}^{\circ}\)C: \({}^{1}\)H NMR (CDCl\({}_{3}\), 400 MHz) \(\delta\) ppm 7.63 (d, 2H, \(J\) = 8.2 Hz, Ar-H), 7.38 (s, 1H, \(J\) = 8.2 Hz, Ar-H), 7.33 (s, 1H, \(J\) = 3.2 Hz, 12-H), 2.95 (dd, 1H, \(J\) = 13.6, 2.4 Hz, 18-H), 2.53 (m, 1H, 2-Ha), 2.35 (m, 1H, 2-Hb), 1.20-2.20 (m, methylene and methine protons), 1.19 (s, 3H, 29-H), 1.08 (s, 3H, 29-H), 1.08 (s, 3H, 29-H), 1.03 (s, 3H, 29-H), 1. 2.1.6. General Procedure for the Preparation of 18a-f Using compound 13 instead of compound 1 as raw material, the target products 18a-f were obtained according to the method of preparing 12a and 12b described above. _Compound 3-oxo-oleanolic acid 28-(4-thioacarbamoyl) glycinate_ (18a). Yield: 19%. Bright yellow solid, m.p. : 139.0-140.3 \({}^{\circ}\)C: \({}^{1}\)H NMR (CDCl\({}_{3}\), 400 MHz) \(\delta\) ppm 7.91 (d, 2H, \(J\) = 8.8 Hz, Ar-H), 7.15 (d, 2H, \(J\) = 8.8 Hz, Ar-H), 6.55 (t, 1H, \(J\) = 4.8 Hz, NH), 5.45 (t, 1H, \(J\) = 3.2 Hz, 12-H), 4.38 (dd, 1H, \(J\) = 18.4, 5.2 Hz, 1\({}^{\prime}\)-H), 4.08 (dd, 1H, \(J\) = 18.4, 4.0 Hz, 1\({}^{\prime}\)-H), 2.65 (dd, 1H, \(J\) = 12.8, 3.2 Hz, 18-H), 2.54 (m, 1H, 2-Ha), 2.36 (m, 1H, 2-Hb), 1.19-2.20 (m, 20H, methylene and methine protons), 1.18 (s, 3H, 29-H), 1.08 (s, 3H, 30-H), 1.04 (s, 3H, 26-H), 1.03 (s, 3H, 23-H), 0.91 (s, 3H, 25-H), 0.91 (s, 3H, 27-H), 0.80 (s, 3H, 24-H), NH\({}_{2}\) shows no signal; \({}^{13}\)C NMR (CDCl\({}_{3}\), 100 MHz) \(\delta\) ppm 217.4, 171.6, 171.2, 154.5, 145.0, 133.6, 122.8, 122.5, 109.4, 55.2, 47.4, 46.8, 46.7, 46.4, 42.2, 42.1, 39.3, 39.1, 38.6, 36.7, 34.1, 32.9, 32.7, 31.8, 30.7, 27.3, 26.4, 25.6, 23.7, 23.6, 23.5, 19.5, 16.8, 15.0; HRMS (ESI) Calcd for C\({}_{39}\)H\({}_{55}\)N\({}_{2}\)O\({}_{4}\)S [M + H]\({}^{+}\) 647.3877, found: 647.3872. _Compound 3-oxo-oleanolic acid 28-(4-(5-thioaxo-5H-1,2-dithiol-3-yl) phenyl! glycinate_ (18b). Yield: 28%. Brick red solid, m.p.