Total Synthesis of 2-Hydroxytetracosanolide and 2-Hydroxy-24-oxooctacosanolide By Using an Effective Lactonization

We have developed effective methods for the total synthesis of 2‐hydroxytetracosanolide and 2‐hydroxy‐24‐oxooctacosanolide, the defensive salivary secretions of termites. The former natural product isolated from Armitermes neotenicus, a species of termite that inhabits Guyana, contains a 25‐membered lactone backbone, and the latter, extracted from Pseudacanthoterme springer, an African termite, includes a 29‐membered lactone moiety. The key cyclization to produce the 25‐ or 29‐membered lactone core is performed by using 2‐methyl‐6‐nitrobenzoic anhydride (MNBA) with a stoichiometric amount of 4‐(dimethylamino)pyridine (DMAP) or a catalytic amount of 4‐(dimethylamino)pyridine N‐oxide (DMAPO). Termite rings: The title compounds are found in the salivary secretions of termites. They can be synthesized by using a combination of 2‐methyl‐6‐nitrobenzoic anhydride (MNBA) and 4‐(dimethylamino)pyridine (DMAP) or 4‐(dimethylamino)pyridine N‐oxide (DMAPO) to produce their macrocyclic lactone cores.