Chemical Synthesis of a Very Long-Chain Fatty Acid, Hexacosanoic Acid (C26:0), and the Ceramide Containing Hexacosanoic Acid

Abstract

Hexacosanoic acid (C26:0) (1), a very long-chain fatty acid, is related to various diseases such as adrenoleukodystrophy (ALD), adrenomyeloneuropathy (AMN) and atherosclerosis. As the level of 1 higher than the normal is related to diseases above, hexacosanoic acid (1) and the ceramide 2, which contains 1, are thought to play an important role in various tissues. Hexacosanoic acid (1) is known to be a waxy solid and to be hard to dissolve in water as well as organic solvents. Due to this physical property, it is not easy to handle hexacosanoic acid (1) in a laboratory. Therefore, efficient chemical synthesis of the compounds 1 and 2 has not been reported. Here, we report a versatile synthetic method for hexacosanoic acid (1) and the ceramide 2 containing the fatty acid 1. Synthesis of hexacosanoic acid (1) was achieved by applying the coupling of two alkyl units as a key step. Ceramide 2 was efficiently synthesized by applying the reported procedure together with hexacosanoic acid (1) synthesized here. This synthetic strategy has an advantage of getting various carbon chain length fatty acids and their ceramides by using a variety of carbon chain units. This method is also applicable for large-scale synthesis. In addition, these compounds 1 and 2 are useful for investigation of details of these compounds related to diseases such as ALD and AMN.