Identification and Total Synthesis of Two Previously Unreported Odd-Chain Bis-Methylene-Interrupted Fatty Acids with a Terminal Olefin that Activate Protein Phosphatase, Mg²⁺/Mn²⁺-Dependent 1A (PPM1A) in Ovaries of the Limpet <i>Cellana toreuma</i>

• Main Authors: Hideki Kawashima, Naoki Toyooka, Takuya Okada, Huy Du Nguyen, Yuya Nishikawa, Yuka Miura, Nana Inoue, Ken-ichi Kimura
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Marine Drugs
• Subjects: non-methylene-interrupted fatty acids; bis-methylene-interrupted dienoic acids; limpet; <i>Cellana toreuma</i>; cytotoxicity; (12<i>Z</i>)-12,16-heptadecadienoic acid; (14<i>Z</i>)-14,18-nonadecadienoic acid; equivalent chain length; protein phosphatase, Mg²⁺/Mn²⁺-dependent 1A (PPM1A)
• Online Access: https://www.mdpi.com/1660-3397/17/7/410

Diverse non-methylene-interrupted (NMI) fatty acids (FAs) with odd-chain lengths have been recognized in triacylglycerols and polar lipids from the ovaries of the limpet <i>Cellana toreuma</i>, however their biological properties remain unclear. In this study, two previously unreported odd-chain NMI FAs, (12<i>Z</i>)-12,16-heptadecadienoic (<b>1</b>) and (14<i>Z</i>)-14,18-nonadecadienoic (<b>2</b>) acids, from the ovary lipids of <i>C. toreuma</i> were identified by a combination of equivalent chain length (ECL) values of their methyl esters and capillary gas chromatography-mass spectrometry (GC-MS) of their 3-pyridylcarbinol derivatives. On the basis of the experimental results, both <b>1</b> and <b>2</b> were synthesized to prove their structural assignments and to test their biological activity. The ECL values and electron impact-mass (EI-MS) spectra of naturally occurring <b>1</b> and <b>2</b> were in agreement with those of the synthesized <b>1</b> and <b>2</b>. In an in vitro assay, both <b>1</b> and <b>2</b> activated protein phosphatase, Mg²⁺/Mn²⁺-dependent 1A (PPM1A) up to 100 &#956;M in a dose-dependent manner.