Synthesis of the Tetraketide Lactones from the Pikromycin Biosynthetic Pathway

Abstract

Synthesis of tetraketide lactones 2 and 3 , which are likely to be produced by a model pikromycin polyketide synthase (PKS), has been investigated. The tetraketide lactones with six-membered rings, 2a and 2b , were synthesized successfully by the asymmetric aldol reaction, allylation, and the Reformatsky reaction. The attempted synthesis of tetraketide lactones with eight-membered rings, 3a and 3b , led to the formation of the compounds 2a and 2b . The synthesis of another tetraketide lactone compounds 35 was attempted with the hope that introducing an additional methyl group would lead to a change in thermodynamic stability. However, it produced the corresponding tetraketide lactone 34 with a six-membered ring. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)