Yakushinamides, Polyoxygenated Fatty Acid Amides That Inhibit HDACs and SIRTs, from the Marine Sponge Theonella swinhoei

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2016-09, Vol.79 (9), p.2384-2390
• Main Authors: Takada, Kentaro, Imae, Yasufumi, Ise, Yuji, Ohtsuka, Susumu, Ito, Akihiro, Okada, Shigeru, Yoshida, Minoru, Matsunaga, Shigeki
• Format: Article
• Language: English
• Subjects: Amides - chemistry; Amides - isolation & purification; Amides - pharmacology; Animals; Fatty Acids - chemistry; Fatty Acids - isolation & purification; Fatty Acids - pharmacology; Histone Deacetylases; Japan; Marine Biology; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Oceans and Seas; Peptides, Cyclic - chemistry; Theonella - chemistry
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.6b00588

Yakushinamides A (1) and B (2), prolyl amides of polyoxygenated fatty acids, have been isolated from the marine sponge Theonella swinhoei as inhibitors of HDACs and SIRTs. Their planar structures were determined by interpretation of the NMR data of the intact molecules and tandem FABMS data of the methanolysis products. For the assignment of the relative configurations of the three contiguous oxymethine carbons in 1 and 2, Kishi’s universal NMR database was applied to the methanolysis products. During the assignments of relative configurations of the isolated 1-hydroxy-3-methyl moiety in 1 and the isolated 1-hydroxy-2-methyl moiety in 2, we found diagnostic NMR features to distinguish each pair of diastereomers. The absolute configurations of 1 and 2 were determined by a combination of the modified Mosher’s method and Marfey’s method. Although the modified Mosher’s method was successfully applied to the methanolysis product of 1, this method gave an ambiguous result at C-20 when applied to the methanolysis product of 2, even after oxidative cleavage of the C-14 and C-15 bond.