Isolation of a novel protein tyrosine phosphatase inhibitor, 2-methyl-fervenulone, and its precursors from Streptomyces

High-throughput screening identified an extract from Streptomyces sp, IM 20 96 with inhibitory activity toward several protein tyrosine phosphatases (P TPs). Four 1,2,4-triazine compounds 2096A-D (1-4) were isolated from this e xtract and their structures elucidated by interpretation of spectroscopic d ata and confirmed by degradation and synthesis. The novel glycocyamidine de rivatives 1 and 2 are diastereomers and may interconvert. Both are inactive in the PTP inhibition assay. Compounds 1 and 2 are unstable and partially decompose to 3 and glycocyamidine (5) at room temperature. Compound 3, know n as MSD-92 or 2-methyl-fervenulone, is a broad-specificity PTP inhibitor w ith comparable potency to vanadate. The imidazo[4,5-e]-1,2,4-triazine (4), inactive in the PTP-inhibition assay, may be a degradation product of 3.