**1. Introduction**

Humans have always struggled against infectious diseases [1–5] and in relatively recent times have developed various antimicrobial therapies [6–8]. Since the discovery of penicillin [9], various natural products having antimicrobial activity have been discovered [10–16], and the majority of clinically used antibiotics are either natural products, semisynthetic derivatives, or compounds derived from them [17–19]. Despite the presence of many excellent antibiotics, multidrug-resistant bacterial pathogens have emerged all over the world [20–22], and the development of novel and effective antimicrobial agents against many kinds of pathogenic bacteria, including methicillin-resistant *Staphylococcus aureus* (MRSA), should remain a continuous mission for medicinal chemists. In 2014, Wang and co-workers discovered eurotiumides, which are novel dihydroisocoumarin-type natural products, from a gorgonian-derived fungus, *Eurotium* sp. XS-200900E6 [23]. Among the series of eurotiumides, eurotiumide A (**1**), having *cis* configurations at H3/H4, exhibited potent antimicrobial activities against *Staphylococcus epidermidis*, *Bacillus cereus*, *Vibrio anguillarum*, and *Escherichia coli*. Based on that report, although **1** seems to be an attractive seed compound for antibiotics, further antimicrobial investigation and a structure–activity relationship study of **1** are needed. In particular, because there is a chance that modification of the side chain of the aromatic ring could improve antimicrobial activity and the spectrum, a structure–activity relationship study of the substituent effect of the aromatic ring is essential for discovering promising candidates for antimicrobial agents. Recently, we reported the first asymmetric total syntheses of (−)-eurotiumide A (**1**) and (+)-eurotiumide B and revised their reported structures [24]. In our synthetic route, the prenyl side chain of the aromatic ring was introduced in the late stage by the Stille coupling reaction with the key intermediate **2**. Based on our previous results, we considered that a number of derivatives of **1**, which have a variety of kinds of side-chain moiety, could be obtained from the common intermediate **2** and non-substituted compound **3** in the late stage of synthesis (Figure 1).

**Figure 1.** Concept of construction of the chemical library of the side chain-derivatives of eurotiumide A (**1**).

In this work, as part of our continuing research [24,25], we constructed a chemical library of the side-chain derivatives of eurotiumide A (**1**) to elucidate the effects of the side chains of the aromatic rings and to develop antimicrobial agents against methicillin-susceptible *S. aureus* (MSSA) and methicillin-resistant *S. aureus* (both Gram-positive bacteria), as well as *Porphyromonas gingivalis* (a Gram-negative bacterium).
