Cycloheximide has been converted by a series of reactions into a dideoxycycloheximide which was found to be optically active. This observation establishes that the methyl groups in dideoxycyclohrximide are oriented in a trans manner. The significance of this result and an interpretation of the stereochemistry of certain other products are presented. YCLOHESIM[DE, a ghtarimide antibiotic whkh C was isolated from Streptomyces griseus, EXhibits antifungal and antitumor activity. Since the initial discovery of cycloheximide (l), several reports have appeared which describe the isolation of certain stereoisomers of this antibiotic. Okuda and co-workers have isolated naramycin A, naramycin B, and a-epi-isocycloheximide frcm Streptomyces naraenses notlo; it has been established that naramycin A is identical with cycloheximide and that naramycin B and a-epi-isocycloheximide are stereoisomers of cycloheximide (2-4).
Later, Lemin and Ford described the isolation of isocycloheximide from S. griseus and showed that isocycloheximide could be formed by the isomerizatjon of cycloheximide with aciddeactivated alumina (5). Thus, there are four known antibiotics which are stereoisomeric to each other. We became interested in determining the stereochemistry of cycloheximide and have reported certain preliminary results of our study (see footnote) ; this paper gives the complete details of this work and discusses the stereochemistry of certain degradation products of cycloheximide.
The method which we selected for the determination of the stereochemistry of the methyl groups involved the removal of the keto arid hydroxyl groups of cycloheximide to form a dideoxy compound. Since the dideoxy cornpound would have methyl groups a t the 1,3-po:.itions and the glutarimide side chain at the 3position, it could exist in a D (or L) form or in a meso-configuration. Therefore, the determin:ition of the optical activity of the dideoxy compound would determine the relative configuratirm of the methyl groups because the compound with &methyl groups has a plane of symmetry . ~~