3.1 Product synthesis
As shown in Figure 2 , ethyl C18-iso -fatty acid arginate derivatives such as ethyl iso -oleoyl arginate hydrochloride(1) and ethyl iso -stearoyl arginate hydrochloride(2) , and three other related species were successfullys ynthesized, using a protocol similar to that reported by Mehtaet al . (2014) but with some major modifications. First, Mehtaet al . (2014) primarily focused on the C12 fatty acid feedstock, although their claims also contained C12 to C20 fatty acids. Second, the synthesis of the fatty acid halides was not provided, whereas this study focused on a variety of fatty acid arginates, especiallyiso -fatty acids, for which their halide forms are not commercially available. Therefore, synthesizing of these intermediates are necessary for this project. Third, there is very little information reported in characterizing the products. Extensive characteristic results were provided using ATR-FT-IR, NMR, and MS to analyze the synthesized fatty acid arginates.
As shown in Figure 2 , a two-step process was used to make the products. For example, in the first step, the iso -oleic acid reacted with thionyl chloride to form an intermediate that expels a chloride anion. The produced chloride anion was added to the carbonyl carbon through nucleophilic addition. Then [1,2]-elimination reaction took place to produce iso -oleoyl chloride, SO2 and hydrochloride (SFig. 1 ,Supplementary Information ). To follow the reaction progress, ∼10 mg was sampled from the mixture every 30 minutes for analysis with/by ATR-FT-IR. It was found that 2 hours were needed for complete conversion without further purification needed. In the next step, theiso -oleoyl chloride was reacted with arginate hydrochloride in anhydrous DMF to produce fatty acid arginate hydrochloride. In this reaction, the lone pair of electrons on primary amine nitrogen of arginate hydrogen forms a bond with the carbonyl carbon of the fatty acid via a nucleophilic attack. Then expulsion of chloride ion and deprotonation took place as shown in the mechanism to obtainiso -oleoyl arginate hydrochloride (SFig. 1 ,Supplementary Information ). It was found that the DMF should be anhydrous to ensure completion of the reaction. This two-step method could also be applied on the C18 n -fatty acids (i.e., oleic acid) to give the ethyl n -oleoyl arginate derivative (Fig. 2, structure 3 ). To obtain the saturated form of the arginated products, they can be processed through a hydrogenation step in the presence of a palladium on carbon catalyst to give the saturated products (i.e., ethyln -stearoyl arginate and ethyl iso -stearoyl arginate) at a quantitative yield (Fig. 2, structures 2&4 ).
The ethyl lauroyl arginate hydrochloride product (Fig. 2, structure 5 ) was also synthesized and thoroughly characterized to compare that against the literature reported results. We found that the product can be easily made using the two-step method, where the first step can be obtained at quantitative yield without further purification needed and the second step obtained at 91% yield with the crude product passed through a short silica gel flash column.