*2.2. Proposed Mechanism for the Formation of Compounds* **1**–**5**

To the best of our knowledge, this is the first report to delineate the possible role that processing plays in producing new chemical entities and impacting the chemical composition of traditional medicines. Five new compounds (**1**–**5**) were generated as a result of the processing of RAM by stir-frying with wheat bran. A plausible rationale for the formation of new atractylon derivatives (**1**–**5**) is outlined below. Both RAM and wheat bran contain fiber, polysaccharides, cellulose, resistant starch, inulin, lignins, and oligosaccharides [1,24]. Thermal processing of cellulose, hemicellulose, and other polysaccharides are known to produce significant amounts of diverse carbonyl compounds such as formaldehyde [25], acetaldehyde, furfural, 5-hydroxymethylfurfural, etc. [26]. Isolation of major quantities of both 5-(hydroxymethyl)furfural (**6**) and 5-(hydroxymethyl)-2-(dimethoxymethyl)furan (**7**) from the processed RAM in this study further supports the formation of carbonyl compounds. On the other hand, atractylon, the major sesquiterpene of *A. macrocephala* [15,27], can undergo electrophilic reactions with the pyrolytic aldehyde products. For example, as shown in the proposed plausible mechanism (Figure 2), atractylon would undergo electrophilic addition with RCHO (R can be hydrogen, methyl, 2-furanyl, or 5-hydroxymethylfuranyl) to yield a carbinol intermediate (**A**). Under pyrolytic conditions, the resulting carbinol would yield electrophilic species (**B**), which can be added to another molecule of atractylon to form an adduct (**C**). Further deprotonation would yield thermally stable

adducts **1**–**4**. Moreover, compound **4** can undergo the same set of reactions (generation of electrophilic species, and addition to another molecule of atractylon and dehydration) to form compound **5**.

**Figure 2.** Proposed mechanism for the generation of compounds **1**–**5**.
