*3.3. Synthesis of 4 and 5*

Compounds **4** and **5** were synthesized according to the reported procedures with minor modifications [17]. Borane-tetrahydrofuran (Borane-THF, 4 mL, 4 mmol) was added dropwise to *L*- or *D*-cysteine (0.121 g, 1 mmol) in dry THF (5 mL) at 0◦C under a nitrogen atmosphere, and stirred at ambient temperature for 7 h. The reaction mixture was quenched with dry dimethylfomamide (DMF, 1 mL) and stirred for 1 h. Farnesyl chloride (0.5 mmol) was added to the reaction mixture and stirred at room temperature for 3 h. The volatiles were removed in vacuo. The residue was re-dissolved in EtOAC (20 mL) and washed with H2O (20 mL) to remove the residue of cysteine. The EtOAc layer was evaporated under reduced pressure and the residue was purified by a semi-preparative HPLC using CH3OH/H2O (87:13) as an eluent to yield farnesyl-*L*-cysteinol (**6**) or farnesyl-*D*-cysteinol (**7**) (Figures S16 and S17).

To a dry DMF solution (500 μL) of **6** or **7** (5.0 mg) and *N*-acetylglycine (2.0 mg), benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP, 12.0 mg), hydroxybenzotriazole (HOBT, 3.0 mg), and *N*-methylmorpholine (300 μL) were added [18]. The reaction mixture was stirred for 3 h at room temperature. Afterwards, 10 mL of water were added and the mixture was extracted twice with EtOAc (15 mL × 2). The EtOAC layer was dried, and the residue was purified by a semi-preparative HPLC (YMC-ODS column, 10 × 250 mm; MeCN-H2O, 65:35) to give compounds **4** or **5** with an overall yield of 11%.

1-farnesyl-2-(*N*-aetylglycine)-*L*-cysteinol (**4**): white amorphous solid, [α] 20 <sup>D</sup> − 110 (c 0.3, MeOH), 1H NMR (600 MHz, MeOD) *δ*<sup>H</sup> 5.23 (t, *J* = 7.8 Hz, 1H), 5.14–5.07 (m, 2H), 4.05–4.00 (m, 1H), 3.90–3.82 (m, 2H), 3.64 (dd, *J* = 11.2, 5.2 Hz, 1H), 3.60 (dd, *J* = 11.1, 4.9 Hz, 1H), 3.22 (dd, *J* = 13.1, 8.0 Hz, 1H), 3.16 (dd, *J* = 13.1, 7.6 Hz, 1H), 2.70 (dd, *J* = 13.7, 6.5 Hz, 1H), 2.55 (dd, *J* = 13.7, 7.4 Hz, 1H), 2.11 (dt, *J* = 11.4, 5.8 Hz, 2H), 2.06 (dt, *J* = 14.2, 7.2 Hz, 4H), 2.01 (d, *J* = 1.0 Hz, 3H), 1.97 (t, *J* = 7.6 Hz, 2H), 1.68 (d, *J* = 7.2 Hz, 6H), 1.60 (s, 6H); 13C NMR (150 MHz, MeOD) *δ*<sup>C</sup> 173.8, 171.4, 140.1, 136.2, 132.1, 125.4, 125.2, 121.8, 63.6, 52.3, 43.6, 40.8, 40.7, 32.9, 30.4, 27.8, 27.5, 25.9, 22.5, 17.8, 16.2, 16.1; ESIMS *m*/*z* 433.2 [M + Na]<sup>+</sup> (Figures S18–S22).

1-farnesyl-2-(*N*-aetylglycine)-*D*-cysteinol (**5**): white amorphous solid, [α] 20 <sup>D</sup> + 120 (c 0.3, MeOH), 1H and 13C NMR, and ESIMS data of **5** were identical to those of **4** (Figures S23–S24).

## *3.4. Anti-Inflammatory Assay*

Anti-inflammatory assay was conducted as described earlier [19]. Murine monocyte/macrophage RAW 264.7 (ATCC TIB-71) cell line was purchased from American Type Culture Collection (ATCC; Manassas, VA, USA).
