Edited by Dennis R. VoelkerFatty acid esters of hydroxy fatty acids (FAHFAs) are a recently discovered class of biologically active lipids. Here we identify the linoleic acid ester of 13-hydroxy linoleic acid (13-LAHLA) as an anti-inflammatory lipid. An oat oil fraction and FAHFA-enriched extract from this fraction showed anti-inflammatory activity in a lipopolysaccharide-induced cytokine secretion assay. Structural studies identified three LAHLA isomers (15-, 13-, and 9-LAHLA) as being the most abundant FAHFAs in the oat oil fraction. Of these LAHLAs, 13-LAHLA is the most abundant LAHLA isomer in human serum after ingestion of liposomes made of fractionated oat oil, and it is also the most abundant endogenous LAHLA in mouse and human adipose tissue. As a result, we chemically synthesized 13-LAHLA for biological assays. 13-LAHLA suppresses lipopolysaccharide-stimulated secretion of cytokines and expression of pro-inflammatory genes. These studies identify LAHLAs as an evolutionarily conserved lipid with anti-inflammatory activity in mammalian cells.Fatty acid esters of hydroxy fatty acids (FAHFAs) 4 are a recently discovered class of lipids with anti-diabetic and anti-inflammatory activity (1). Because there are numerous FAHFAs, they are classified into families based on the composition of fatty acid and hydroxy fatty acid. For example, palmitic acid esters of hydroxy stearic acids (PAHSAs) and oleic acid esters of hydroxy stearic acids (OAHSAs) are two FAHFA families. Furthermore, within a FAHFA family, there are multiple regioisomers that differ in the position of the ester linkage (e.g. 5-PAHSA and 9-PAHSA) (1).Biological testing of 5-and 9-PAHSA revealed potent antidiabetic and anti-inflammatory activity (1-3). Mechanistic studies revealed that FAHFAs regulate several cellular and physiological pathways, with at least some of the biology being attributable to agonism of GPR120 and GPR40, two G proteincoupled receptors (1, 3). Other ligands for these G proteincoupled receptors include saturated and polyunsaturated fatty acids (4, 5). GPR120 is the endogenous receptor for omega-3 fatty acids, and it mediates the anti-inflammatory effects of these lipids (5).The anti-inflammatory activity of FAHFAs has been reported in vitro and in vivo (1, 2). Initially, cellular experiments with bone marrow-derived dendritic cells showed that treatment of cells with 9-PAHSA reduced the amplitude of cytokine secretion and expression of cellular inflammation markers. In addition, administration of 9-PAHSA to mice on a high-fat diet reduced inflammation in adipose tissue of treated mice (1). 9-PAHSA also showed robust anti-inflammatory activity in a mouse colitis model. Administration of 9-PAHSA to mice undergoing chemically induced colitis improved clinical and molecular inflammation (2). Moreover, an analysis of the impact of 9-PAHSA on the immune system revealed effects on the innate and adaptive immune system (2). Most recently, Kuda et al. (6) demonstrated that docosahexaenoic acid of 13-hydroxy linoleic acid (13-DHAHLA), a...

The syntheses of linoleic acid esters of hydroxy linoleic acids (LAHLAs) present in oat oil and human serum have been achieved, providing access to material for testing and the determination of the stereochemistry of the natural compounds. While 9- and 13-LAHLAs were found to be a mixture of enantiomers 15-LAHLA is generated in a single optical form in oat oil. The stereochemistry of 15-LAHLA in oat oil was found to be opposite to that reported for digalactosyldiacylglycerol that possesses an embedded 15-LAHLA.

Thiopeptides are a class of natural products with untapped therapeutic potential. To expand the methods available for the scaled production of these antibiotics, we report the laboratory synthesis of micrococcin P1 showcasing thiazole forming reactions of cysteine derivatives and nitriles followed by oxidation. In most instances, this thiazole forming sequence does not require chromatography and proved scalable. Using this approach, 199 mg of micrococcin P1 was generated in a single synthetic sequence.