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.