Synthesis of the antifungal natural compound Farinomalein and analogues

Recently, a three-step synthesis of Farinomalein has been reported by Miles and Yan.[2]. However, the Authors themselves state that their synthesis is difficult to scale-up due to the use of hazardous and expensive oxidant Dess-Martin periodinane. Here we report a different synthetic approach to Farinomalein, developed in four steps with high yield and without using any hazardous chemical. The new synthesis is flexible and convenient, starting from readily available ethyl 3-methyl-2-oxobutyrate and triethyl phosphonoacetate and employing a Horner-Wadsworth-Emmons condensation as the key step. The procedure was scaled up to 10 g batches. The methodology was used to prepare different analogues, to support structure-activity relationship studies. The antifungal activity of Farinomalein and its analogues was tested against various fungi.