Ascofuranone

Ascofuranone is an antibiotic produced by various ascomycete fungi including Acremonium sclerotigenum[1] that inhibits the Trypanosoma brucei alternative oxidase and is a lead compound in efforts to produce other drugs targeting this enzyme for the treatment of sleeping sickness.

[2] The compound is effective both in vitro cell culture and in infections in mice.

Expodiation of (3) by AscE (P450 monooxygenase) leads to the formation of ilicicolin A epoxide (4).

Ilicicolin A epoxide can then be hydroxylated by AscH at C-16 (P450 monooygenase) to yield intermediate (5) which can then be cyclized by AscI (eight-transmembrane protein, TPC) into ascofuranol (6), specifically through 6-endo-tet cyclization.

Finally, ascofuranol (6) can be oxidized by AscJ (NAD(P)-dependent alcohol dehydrogenase) leading to the formation of ascofuranone.

Structural formula of ascofuranone
Space-filling model of the ascofuranone molecule
Biosynthetic Pathway