*Article* **Synthesis and Antimicrobial Evaluation of Side-Chain Derivatives based on Eurotiumide A**

**Atsushi Nakayama 1,\*, Hideo Sato 1, Tenta Nakamura 1, Mai Hamada 1, Shuji Nagano 1, Shuhei Kameyama 1, Yui Furue 2, Naoki Hayashi 2, Go Kamoshida 2, Sangita Karanjit 1, Masataka Oda <sup>2</sup> and Kosuke Namba 1,\***


Received: 30 November 2019; Accepted: 29 January 2020; Published: 30 January 2020

**Abstract:** Side-chain derivatives of eurotiumide A, a dihydroisochroman-type natural product, have been synthesized and their antimicrobial activities described. Sixteen derivatives were synthesized from a key intermediate of the total synthesis of eurotiumide A, and their antimicrobial activities against two Gram-positive bacteria, methicillin-susceptible and methicillin-resistant *Staphylococcus aureus* (MSSA and MRSA), and a Gram-negative bacterium, *Porphyromonas gingivalis*, were evaluated. The results showed that derivatives having an iodine atom on their aromatic ring instead of the prenyl moiety displayed better antimicrobial activity than eurotiumide A against MSSA and *P. gingivalis*. Moreover, we discovered that a derivative with an isopentyl side chain, which is a hydrogenated product of eurotiumide A, is the strongest antimicrobial agent against all three strains, including MRSA.

**Keywords:** antibiotics; natural product; *P. gingivalis*; methicillin-resistant *S. aureus*
