# 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**
: 107.9-109.1 \({}^{\circ}\)C: \({}^{1}\)H NMR (CDCl\({}_{3}\), 400 MHz) \(\delta\) ppm 7.57 (d, 2H, \(J\) = 8.8 Hz, Ar-H), 7.14 (d, 2H, \(J\) = 8.8 Hz, Ar-H), 7.13 (s, 1H, \(8^{\prime\prime}\)-H), 6.41 (t, 1H, \(J\) = 4.8 Hz, NH), 5.33 (t, 1H, \(J\) = 3.2 Hz, 12-H), 4.28 (dd, 1H, \(J\) = 18.4, 5.6 Hz, \(1^{\prime}\)-H), 3.96 (dd, 1H, \(J\) = 18.4, 4.0 Hz, \(1^{\prime}\)-H), 2.52 (dd, 1H, \(J\) = 12.8, 3.2 Hz, 18-H), 2.42 (m, 1H, 2-Ha), 2.23 (m, 1H, 2-Hb), 1.06-2.20 (m, 20H, methylene and methine protons), 1.05 (s, 3H, 29-H), 0.95 (s, 3H, 30-H), 0.91 (s, 3H, 26-H), 0.90 (s, 3H, 23-H), 0.78 (s, 3H, 25-H), 0.78 (s, 3H, 27-H), 0.68 (s, 3H, 24-H), 1\({}^{3}\)C NMR (CDCl\({}_{3}\), 100 MHz) \(\delta\) ppm 217.5, 215.5, 178.6, 171.3, 168.3, 153.0, 144.5, 136.1, 129.6, 128.3, 123.0, 122.6, 55.2, 47.4, 46.8, 46.6, 46.4, 42.2, 42.1, 41.8, 39.3, 39.1, 36.7, 34.1, 34.0, 32.9, 32.4, 31.8, 30.7, 27.3, 26.4, 25.6, 23.9, 23.6, 23.5, 19.5, 16.5, 15.0; HRMS (ESI) Calcd for C\({}_{41}\)H\({}_{54}\)NO\({}_{4}\)S\({}_{3}\) [M + H]\({}^{+}\) 720.3209, found: 720.3215. _Compound 3-oxo-oleanolic acid 28-(4-carbamoyltioylphenyl!) carboxamide propanoate_ (18c). Yield: 15%. Yellow solid, m.p. : 161.6-162.9 \({}^{\circ}\)C: \({}^{1}\)H NMR (CDCl\({}_{3}\), 400 MHz) \(\delta\) ppm 7.90 (d, 2H, \(J\) = 8.8 Hz, Ar-H), 7.12 (d, 2H, \(J\) = 8.8 Hz, Ar-H), 6.06 (t, 1H, \(J\) = 5.2 Hz, NH), 5.34 (t, 1H, \(J\) = 3.2 Hz, 12-H), 3.50 (m, 1H, \(I\)'-H), 3.14 (m, 1H, 1\({}^{\prime}\)-H), 2.80 (m, 1H, 18-H), 2.66 (m, 1H, 2-Ha), 2.40 (m, 2H, 2\({}^{\prime}\)-H), 2.26 (m, 1H, 2-Hb), 2.40 (m, 2H, 2\({}^{\prime}\)-H), 2.22 (m, 1H, 2-Hb), 1.18-2.20 (m, 20H, methylene and methine protons), 1.17 (s, 3H, 29-H), 1.08 (s, 3H, 30-H), 1.03 (s, 3H, 26-H), 1.01 (s, 3H, 23-H), 0.90 (s, 3H, 25-H), 1.08 (s, 3H, 25-H), 1.08 (s, 3H, 25-H), 1.08 (s, 3H, 25-H), 1.08 (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, 46.7, 46.6, 44.2, 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\({}_{40}\)H\({}_{57}\)N\({}_{2}\)O\({}_{4}\)S [M + H]\({}^{+}\) 661.4034, found: 661.4036. _Compound 3-oxo-oleanolic acid 28-(4-(5-thioaxo-5H-1,2-dithiol-3-yl) phenyl!) carboxamide propanoate_ (18d). Yield: 23%. Brick red solid, m.p. : 113.5-114.7 \({}^{\circ}\)C: \({}^{1}\)H NMR (CDCl\({}_{3}\), 400 MHz) \(\delta\) ppm 7.55 (d, 2H, \(J\) = 8.4 Hz, Ar-H), 7.12 (s, 1H, \(8^{\prime\prime}\)-H), 7.11 (d, 2H, \(J\) = 8.4 Hz, Ar-H), 6.28 (t, 1H, \(J\) = 5.6 Hz, NH), 5.24 (t, 1H, \(J\) = 3.2 Hz, 12-H), 3.62 (m, 1H, \(1^{\prime}\)-H), 3.31 (m, 1H, \(1^{\prime}\)-H), 2.73 (m, 1H, 18-H), 2.66 (m, 1H, 2-Ha), 2.40 (m, 2H, \(2^{\prime}\)-H), 2.22 (m, 1H, 2-Hb), 1.04-2.20 (m, 20H, methylene and methine protons), 1.03 (s, 3H, 29-H), 0.94 (s, 3H, 30-H), 0.90 (s, 3H, 26-H), 0.86 (s, 3H,and methine protons), 1.17 (s, 3H, 29-H), 1.08 (s, 3H, 30-H), 1.03 (s, 3H, 26-H), 1.03 (s, 3H, 23-H), 0.90 (s, 3H, 25-H), 0.88 (s, 3H, 27-H), 0.81 (s, 3H, 24-H); 13C NMR (CDCl\({}_{3}\), 100 MHz) 8 ppm 217.4, 171.6, 171.2, 154.5, 145.0, 133.6, 122.8, 122.5, 109.4, 55.2, 47.4, 46.7, 46.6, 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, 24.6, 23.7, 23.6, 23.5, 21.4, 19.5, 16.8, 15.0; HRMS (ESI) Calcd for C\({}_{41}\)H\({}_{59}\)N\({}_{2}\)O\({}_{4}\)S [M + H]\({}^{+}\) 675.4190, found: 675.4189. _Oleanolic acid 28-[4-(5-thiazol-3-yl) phenyl] carboxamido butanoate_ (**18f**). Yield: 25%. Red brown solid, m.p.