The characterization of the structure of mumbaistatin (
1), an effective inhibitor of the glucose-6-phosphatase system (EC 3.1.3.9), is reported. Isolation of mumbaistatin from cultures of
Streptomyces sp. DSM 11641 was achieved by anion-exchange and reversed-phase chromatography. The acid-labile inhibitor was methylated for the structure determination. Single-crystal X-ray structure analysis of a triply methylated dehydration product, C
31H
24O
11, revealed the structure of an aromatic dispirodiketal (
2), a compound containing a previously undescribed ring system. Extensive 2D-NMR experiments with mumbaistatin and with the methylation products showed that mumbaistatin itself possesses the hydroxydiketodicarboxylic acid structure
1, C
28H
20O
12, which, in the presence of acid or upon activation through methyl ester formation, undergoes self-condensation with loss of water to the dispirodiketal form (
2). Mumbaistatin is an anthraquinone derivative, whose open-chain diketo form acts as a specific and powerful inhibitor of glucose-6-phosphate translocase: IC
50=5nM. The activity towards the same enzyme of the cyclized dispirodiketal derivatives is roughly one thousand times lower.
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