*2.1. Chemistry*

The main approach to producing 4-arylcoumarins unsubstituted at the hydroxy group is acid-catalyzed Pechmann condensation between resorcinol **4** and ester of β-keto-carboxylic acids **5** [63] (Scheme 1). Using this approach, we synthesized 7-hydroxy-4-arylcoumarins **6a–d** with yields of 63-81% by interaction of resorcinol **4** with esters **5a–d** (Scheme 1). Ester **5a** is commercially available, while compounds **5b–d** were obtained by the reaction of substituted acetophenones **5b–d** with diethyl carbonate in the presence of sodium hydride.

**Scheme 1.** Synthesis of 7-hydroxy-4-arylcoumarins **6a–d.**

Monoterpenoid bromides **8a–d** were obtained from the corresponding alcohols (geraniol, (−)-nopol, (−)- and (+)-myrtenols) by interaction with PBr<sup>3</sup> according to the procedure [46] (Scheme 2). Geraniol and (−)-nopol were purchased from commercial sources, while (−)- and (+)-myrtenols were synthesized from (−)-myrtenal and (+)-α-pinene in accordance with the methods [46]. The choice of monoterpenoids was based on the results we obtained previously, i.e., when both the absolute configuration of the pinane cycle and the length of the bridge played important roles [46]. A further consideration was the desire to compare the activity data obtained with bulky bicyclic substituents with corresponding data for products with acyclic monoterpene fragments. Note that coumarin-containing derivatives of geraniol can be considered as analogues of the natural coumarin auraptene, having the same monoterpenoid fragment (Figure 1).

**Scheme 2.** Synthesis of monoterpenoid bromides **8a–d**.

The target monoterpenoid-arylcoumarin hybrids **3** were synthesized by the reaction of 7-hydroxycoumarins **6a–d** with monoterpenoid bromides **8a–d** using DBU in DMF (Scheme 3). To compare and identify the importance of the monoterpenoid fragment, compounds **10a, c, d** containing a benzyl substituent were also synthesized. The products were purified by recrystallization or column chromatography, and obtained with yields of 12–65%. In the case of the synthesis of nopol derivatives, a low conversion was observed, and double purification on SiO<sup>2</sup> was required, for example, for compounds **3ab** or **3cb** with yields less than 20%).

**Scheme 3.** Synthesis of monoterpenoid-arylcoumarin hybrids.
