Synthesis of Unnatural Aplysiatoxin Analogs with High Affinity for Protein Kinase C
Aplysiatoxin (ATX) is a marine polyketide macrodiolide and a potent activator of protein kinase C (PKC), which results in a variety of biological events, including inflammation and tumor promotion. This synthetic study of ATX leads to the serendipitous discovery of macrodiolide 1 , which showed a high affinity for PKCδ despite having a different ring system to ATX. Here, the synthesis of ten analogs of 1 is reported, one of which, unsaturated macrodiolide 26 , showed a higher affinity to PKC than compound 1 .
Authors
- Toshio Nishikawa (ORCID: https://orcid.org/0000-0003-1955-6618)
- Kazuhiro Irie (ORCID: https://orcid.org/0000-0001-7109-8568)
- Keisuke Fukaya (ORCID: https://orcid.org/0000-0002-7148-4714)
- Daisuke Urabe (ORCID: https://orcid.org/0000-0002-1999-9374)
- Mana Morishita
- Ryo C. Yanagita (ORCID: https://orcid.org/0000-0002-9217-5507)
- Kohei Hada
- Jumpei Maki (ORCID: https://orcid.org/0000-0002-7166-4491)
- Yusuke Hanaki (ORCID: https://orcid.org/0000-0002-0591-3429)
- Masaki Kita (ORCID: https://orcid.org/0000-0001-6685-4461)
- Yusuke Araki
Institutions
- Doshisha University (JP)
- Kagawa University (JP)
- Kyoto University (JP)
- Nagoya University (JP)
- Toyama Prefectural University (JP)
Publication Details
- Journal
- European Journal of Organic Chemistry
- Published
- 2025-10-21
- DOI
- https://doi.org/10.1002/ejoc.202500890
- Primary Topic
- Chemical synthesis and alkaloids
- Type
- article
- Field-Weighted Citation Impact
- 0.00