Kodaistatins, novel inhibitors of glucose-6-phosphate translocase T1 from Aspergillus terreus Thom DSM 11247 - Isolation and structural elucidation

Two novel compounds, kodaistatin A, C35H34O11, molecular weight 630, and ko daistatin C, C35H34O12, molecular weight 646, have been isolated from cultu res of Aspergillus terreus Thom DSM 11247 by solid-phase extraction, size-e xclusion chromatography, and various preparative HPLC steps. The use of a r ange of 2D NMR measurements, in particular C-13-C-13 correlation measuremen ts, has led to the clarification of the structure of kodaistatin A. Kodaist atin C is a hydroxylated derivative of kodaistatin A. Both natural products contain hydroxylated aspulvinones and identical highly substituted polyket ide units. An X-ray single crystal structure analysis of aspulvinon E demon strated the z-configuration at the central double bond. The kodaistatins ar e effective inhibitors of the glucose-6-phosphate translocase component of the glucose-6-phosphatase system (EC 3.1.3.9), an enzyme system which is im portant for the control of blood glucose levels. The IC50 is 80 nM for koda istatin A and 130 nM for kodaistatin C.