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>

Abstract

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 Cellana toreuma, however their biological properties remain unclear. In this study, two previously unreported odd-chain NMI FAs, (12Z)-12,16-heptadecadienoic (1) and (14Z)-14,18-nonadecadienoic (2) acids, from the ovary lipids of C. toreuma 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 1 and 2 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 1 and 2 were in agreement with those of the synthesized 1 and 2. In an in vitro assay, both 1 and 2 activated protein phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A) up to 100 μM in a dose-dependent manner.

Keywords

• 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)