The Synthesis of Diepoxide Analogues of Fumagillin

Abstract

Pathways from cyclohexanone to compounds of the general type 4-(1',2'-epoxy-1'-methylalkyl)- 1-oxaspiro[2,5]octane (5), the simplest diepoxide analogues of the antibiotic fumagillin (1a), are described. The sequence involves the initial formation of 6-acetyl-1,4-dioxaspiro[4,5]decane (2a) which is converted into a 2-alkenylcyclohexanone through the Wittig reaction. Subsequent spiro epoxidation of the cyclic ketone and peracid epoxidation of the side chain double bond affords the diepoxides (5a-c). In most respects the synthetic diepoxides possess the same stereochemistry as the equivalent functionality of fumagillin.