2.2 Synthetic procedure
Iso-oleoyl chloride. As shown in Figure 2 ,iso -oleic acid (5 g, 0.017 mol) in 10 mL of dichloromethane was added to in a three-neck round bottom flask equipped with a condenser. The mixture was placed in an ice bath to chill for a couple minutes; thionyl chloride (2.8 mL, 2.2 equiv.) was then added dropwise viaa syringe. The reaction was heated to reflux at 75 oC for 2.0 h. When the reaction was completed and cooled, the residual thionyl chloride and dichloromethane were removed through a vacuum line.Iso -oleoyl chloride was obtained as a viscous yellowish liquid and was used in a subsequent reaction without further purification.
Ethyl iso-oleoyl arginate hydrochloride. L-arginine ethyl hydrochloride (3.7 g, 1.0 equiv. toiso -oleoyl chloride) in 30 mL of anhydrous DMF was added to a 50 mL flask with a side arm attached to the nitrogen line, followed by triethylamine (5.6 mL, 3.0 equiv. to iso-oleoyl chloride). DMF was treated with activated molecular sieves for 24 h before use. The iso -oleoyl chloride (4.0 g, 0.013 mol) was then added to the flask dropwise via an additional funnel. The flask was capped, stirred at room temperature for 15 minutes, and then heated at 50 oC for 2 h. The mixture was dissolved in ethyl acetate and transferred to a separatory funnel. The organic phase was neutralized with saturated sodium bicarbonate solution and then washed with water twice. The product was obtained by removing the organic solvent using rotary evaporator. It was then passed through a 50 mL SPE column using ethyl acetate:methanol eluent with the following gradients (9:1, 8:2, 7:3, 6:4, 3:7) to give the desired ethyliso -oleoyl arginate as a viscous light brown product at 76% yield (Fig. 2, structure 1 ). ATR-FT-IR of the fractionated products spectroscopic data are provided in SFigure 1 (Supplementary Information) and Figures 3&4 .
Ethyl iso-stearoyl arginate hydrochloride. Ethyliso -oleoyl arginate (Fig. 2, structure 1) was converted to ethyl iso -stearoyl arginate hydrochloride (Fig. 2, structure 2) through a general hydrogenation step which can be found in Ngo et al . (2012). Briefly, in a 4-dram glass vial, ethyliso -oleoyl arginate hydrochloride, 1 (200 mg, 0.43 mmol) was dissolved in 5 mL of methanol, added by 5 wt% Pd/C (150 mg). The vial was sealed with a septum cap having a small hole on it. The hole was to allow the hydrogen gas to enter the reaction mixture. The vial was then placed in a 300 mL stainless steel parr reactor where it was sealed, purged with 50 psi of hydrogen gas and reacted for 24 h (3 h for the ethyl n -oleoyl arginate) at RT. After the reaction, the suspension was vacuum filtered through a celite packed funnel to remove the Pd/C. The methanol was evaporated in a rotary evaporator to give the desired ethyl iso -stearoyl arginate at >99% yield.
The same synthetic procedure was applied to obtain ethyl n -oleoyl arginate (Fig. 2, structure 3 ) and ethyl n -stearate arginate (Fig. 2, structure 4 ). Some intermediate and final products spectroscopic data are provided in SFigure 1 (Supplementary Information) and Figures 3&4 . From these experimental results, we can generalize that this two-step process is universal and can be applied to other types of fatty acid feedstocks.
Lauroyl chloride. As shown in Figure 2 , fatty acid such as lauric acid (2.5 g, 0.012 mol) was dissolved in 30 mL of dichloromethane and transferred in a three-neck round bottom flask equipped with a condenser. The mixture was placed in an ice bath to chill for a couple minutes, thionyl chloride (2.0 mL, 2.2 equiv.) was then added dropwise via a syringe. The reaction was heated to reflux at 75 oC for 3.0 h. When the reaction was completed and cooled, the residual thionyl chloride and dichloromethane were removed through a vacuum line. Lauroyl chloride was obtained as a viscous yellowish liquid and was used in a subsequent reaction without further purification (Fig. 2 ).
Ethyl lauroyl arginate. L-arginine ethyl hydrochloride (2.3 g, 1.0 equiv. to lauric acid chloride) was dissolved in 15.0 mL of anhydrous DMF. The L-arginine solution was then transferred into a flask attached to a side arm with triethylamine (2.5 mL, 3.0 equiv. to lauric acid chloride) slowly added to it. The lauroyl chloride (1.8 g, 0.0082 mol) was added to the solution dropwise via an dropping funnel. The flask was capped, stirred at room temperature for 15 minutes and then heated at 50 oC for 2 h. The product was extracted with solvent and washed with water. It was then passed through a short silica gel column using an eluent of 1:1 methanol:ethyl acetate solution to give the desired pure ethyl lauroyl arginate (5) as a white solid product at 91% yield.