@article{2c873da65d9248669c7115a085993aef,
title = "Total synthesis and antimicrobial evaluation of (+)-hygrophorone B12 and its analogues",
abstract = "This paper describes the synthesis and evaluation of lead compounds with a new chemical skeleton that is not found in conventional antimicrobial agents. The biologically attractive cyclopentenoid (+)-hygrophorone B12, isolated from the fruiting bodies of Hygrophorus abieticola, and its analogues were synthesized in a longer linear sequence of twelve steps, starting from a cyclopentenone derivative. This synthesis involved the following crucial steps: (i) oximation of a ketone to stabilize the requisite aldehyde to install a side chain and (ii) coupling of an aldehyde with a side chain to assemble the desired hygrophorone. Then, the antimicrobial activity of these hygrophorones towards clinically relevant bacterial pathogens was evaluated. The results showed that hygrophorone B12 and its analogues are especially effective in preventing the proliferation of gram-positive bacteria. In addition, it was found that some structural features such as the presence of the enone moiety as well as the carbon–carbon triple bond on the hydrocarbon chain were pivotal to increase the antimicrobial activity of hygrophorone B. This study is expected to support the development of novel antimicrobial agents by flexibly synthesizing hygrophorone B analogues with a carbon five-membered ring skeleton from the common intermediate.",
author = "Takaaki Kamishima and Masato Suzuki and Koichi Narita and Yoshitaka Koseki and Toshiyuki Nonaka and Hirotaka Nakatsuji and Hideo Hattori and Hitoshi Kasai",
note = "Funding Information: We would like to thank Emeritus Profs. Kunio Arai and Hachiro Nakanishi (Tohoku University) as well as Dr. Jun Hasegawa and Mr. Toshiaki Tanaka (Genesis Research Institute Inc.), who supported our research. This work was performed under the Cooperative Research Program “Network Joint Research Center for Materials and Devices, Grants for Research Program on Emerging, the Research Program of “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” in “Network Joint Research Center for Materials and Devices” and “Re-emerging Infectious Diseases” (JP21fk0108093, JP21fk0108139, JP21fk0108133, JP21wm0325003, JP21wm0325022, JP21wm0225004, JP21wm0225008, and JP21gm1610003 to M.S.) from the Japan Agency for Medical Research and Development (AMED). Funding Information: We would like to thank Emeritus Profs. Kunio Arai and Hachiro Nakanishi (Tohoku University) as well as Dr. Jun Hasegawa and Mr. Toshiaki Tanaka (Genesis Research Institute Inc.), who supported our research. This work was performed under the Cooperative Research Program “Network Joint Research Center for Materials and Devices, Grants for Research Program on Emerging, the Research Program of “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” in “Network Joint Research Center for Materials and Devices” and “Re-emerging Infectious Diseases” (JP21fk0108093, JP21fk0108139, JP21fk0108133, JP21wm0325003, JP21wm0325022, JP21wm0225004, JP21wm0225008, and JP21gm1610003 to M.S.) from the Japan Agency for Medical Research and Development (AMED). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41598-022-11608-8",
language = "English",
volume = "12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}