A new approach to the synthesis of 3,6- and 5,6-dialkyl derivatives of 4-hydroxy-2-pyrone. Synthesis of rac-germicidin

A new approach to the synthesis of 3,6- and 5,6-dialkyl-4-hydroxy-2-pyrones has been developed. The method includes the formation of acylated Meldrum' s acids (5-(2-alkyl-3-oxoacyl)-2,2-dimethyl-1,3-dioxane-4,6-diones) followe d by their thermal transformation. Introduction of 3-alkyl substituents was accomplished by acylation of 4-hydroxy-2-pyrones and ionic hydrogenation o f the 3-acyl derivatives obtained. The effectiveness of this new approach h as been demonstrated in the synthesis of rac-germicidin, an autoregulative germination inhibitor of Streptomyces viridochromogenes NRRL B-1551. (C) 19 99 Elsevier Science Ltd. All rights reserved.