Isocycloheximide

A high-pressure liquid chromatographic procedure is described for the assay of the antibiotic cycloheximidein bulk drug and two experimental formulations. The method utilizes a reversed-phase C18 chromatographic column and refractive index detection. Possible impurities or degradation products, isocycloheximide, anhydrocycloheximide, and dimethylcyclohexone, are well separated from cycloheximide by this procedure. Complete extraction of cycloheximide from the formulations was obtained. The assay has a relative standard deviation of approximately 1%.

Three new cycloheximide congeners, 2,3-dehydro-α-epi-isocycloheximide (1), (E)- and (Z)-2,3-dehydroanhydrocycloheximides (2 and 3), together with three known compounds, anhydroisoheximide (4), cycloheximide (5), and isocycloheximide (6), were obtained from the cultures of Streptomyces sp. SC0581. Their structures were elucidated by extensive spectroscopic analysis in combination with theoretical conformational analysis and ECD computations. The photoinduced interconversion between 2 and 3 was observed and verified and the possible reaction path and mechanism were proposed by theoretical computations. The antifungal and cytotoxic activities of 1-6 were evaluated and suggested that 2,3-dehydrogenation results in the loss of the activities and supported that the OH-α is important to the activities of cycloheximide congeners.

Askostatin is a fungicide isolated from the culture of Streptomyces viridovulgaris. It was separated by the countercurrent distribution procedure into components A and B. By the mass and NMR spectra and the biological findings the components were identified with cycloheximide and isocycloheximide respectively.