# 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
#### 2.1.2 General Procedure for the Preparation of **4a-d**
_Oleanolic acid 3-[((3-(4-carbamoylomethylphenoxy)-3-oxopropyl)disulfanyl)proanoyl] oxyl carboxylic acid_ (**8a**). Yield: 43%. Brown yellow solid, m.p. : 127.4-128.9 \({}^{\circ}\)C: \({}^{1}\)H NMR (CDCl\({}_{3}\), 400 MHz) \(\delta\) ppm 7.90 (d, 2H, \(J\) = 8.2 Hz, Ar-H), 7.15 (d, 2H, \(J\) = 8.2 Hz, Ar-H), 5.30 (t, 1H, \(J\) = 3.6 Hz, 12-H), 4.54 (t, 1H, \(J\) = 7.6 Hz, 3-H), 0.30 (m, 4H, \({}^{1}\)\({}^{\prime}\)-H and 3\({}^{\prime}\)-H), 2.97 (t, 2H, \(J\) = 6.8 Hz, 2\({}^{\prime}\)\({}^{\prime}\)-H), 2.82 (dd, 1H, \(J\) = 13.6, 3.2 Hz, 18-H), 2.75 (t, 2H, \(J\) = 6.8 Hz, 2\({}^{\prime}\)\({}^{\prime}\)-H), 2.82 (dd, 1H, \(J\) = 13.6, 3.2 Hz, 18-H), 2.75 (t, 2H, \(J\) = 6.8 Hz, 2\({}^{\prime}\)\({}^{\prime}\)-H), 2.82 (dd, 1H, \(J\) = 13.6, 3.2 Hz, 18-H), 2.75 (t, 2H, \(J\) = 6.8 Hz, 2\({}^{\prime}\)\({}^{\prime}\)-H), 1.14-2.20 (m, 22H, methylene and methine protons), 1.13 (s, 3H, 29-H), 0.93 (s, 3H, 29-H), 0.93 (s, 3H, 29-H), 0.93 (s, 3H, 29-H), 0.91 (s, 3H, 23-H), 0.88 (s, 3H, 25-H), 0.86 (s, 3H, 27-H), 0.76 (s, 3H, 24-H), COOH and NH\({}_{2}\) show no signal; \({}^{13}\)C NMR (CDCl\({}_{3}\), 100 MHz) \(\delta\) ppm 182.5,173.8, 172.8, 154.5, 143.6, 133.6, 122.8, 122.6, 109.4, 80.5, 55.2, 47.6, 46.5, 45.9, 41.6, 41.0, 39.3, 38.4, 38.0, 37.1, 38.9, 33.1, 32.6, 32.4, 30.7, 30.1, 30.0, 28.1, 27.7, 25.9, 24.7, 23.6, 23.4, 22.9, 18.3, 17.1, 15.5, 15.3; HRMS (ESI) Calcd for C\({}_{43}\)H\({}_{62}\)NO\({}_{6}\)S\({}_{3}\) [M + H]\({}^{+}\) 784.3734, found: 784.3738. _Oleanolic acid 3-[((3-(4-carbamoylomethyl)])] carboxylic acid_ (**8b**). Yield: 40%. Red brown solid, m.p. : 130.8-140.8 \({}^{\circ}\)C: \({}^{1}\)H NMR (CDCl\({}_{3}\), 400 MHz) \(\delta\) ppm 7.68 (d, 2H, \(J\) = 8.2 Hz, Ar-H), 7.40 (s, 1H, \(J\) = 7.26 (d, 2H, \(J\) = 8.2 Hz, Ar-25.9, 24.7, 23.6, 23.4, 22.9, 18.3, 17.1, 15.5, 15.3; HRMS (ESI) Calcd for C45H61O6S5 [M + H]+857.3066, found: 857.3061. _Oleanolic acid 3-[((3-(4-(benzylcarbamothioylphenoxy)-3-oxopropyl)propanamide))] carboxylic acid (**8c**). Yield: 39%. Bright yellow solid, m.p. : 139.5-140.8 \({}^{\circ}\)C: 1\({}^{\circ}\)H NMR (CDCl3, 400 MHz) 8 ppm 7.77 (d, 2H, \(J\) = 8.8 Hz, Ar-H), 7.35-7.40 (m, 5H, Ar-H), 7.11 (d, 2H, \(J\) = 8.8 Hz, Ar-H), 5.27 (t, 1H, \(J\) = 3.6 Hz, 12-H), 4.98 (d, 2H, \(J\) = 5.2 Hz, 1\({}^{\prime\prime\prime}\)-H), 4.53 (t, 1H, \(J\) = 8.0 Hz, 3-H), 3.01 (t, 4H, \(J\) = 3.6 Hz, 1\({}^{\prime\prime}\)-H and 3\({}^{\prime}\)-H), 2.96 (t, 2H, \(J\) = 6.8 Hz, 2\({}^{\prime\prime}\)-H), 2.82 (dd, 1H, \(J\) = 13.6, 3.2 Hz, 18-H), 2.74 (t, 2H, \(J\) = 6.8 Hz, 2\({}^{\prime}\)-H), 1.14-2.20 (m, 22H, methylene and methine protons), 1.13 (s, 3H, 29-H), 0.93 (s, 3H, 30-H), 0.93 (s, 3H, 26-H), 0.91 (s, 3H, 23-H), 0.87 (s, 3H, 25-H), 0.85 (s, 3H, 27-H), 0.75 (s, 3H, 24-H), COOH shows no signal; 13C NMR (CDCl3, 100 MHz) 8 ppm 182.5, 173.8, 172.8, 154.5, 143.6, 134.8, 133.6, 128.6, 128.5, 126.9, 126.7, 122.8 122.6 109.4 80.5, 55.2, 50.4, 47.6, 46.5, 45.9, 41.6, 41.0, 39.3, 38.4, 38.0, 37.1, 33.8, 33.1, 32.6, 32.4, 30.7, 30.3, 30.2, 30.1, 28.1, 27.7, 25.9, 24.7, 23.6, 23.4, 22.9, 18.3, 17.1, 15.5, 15.3; HRMS (ESI) Calcd for C50H68 NO6S3 [M + H]* 874.4203, found: 874.4214.