Stereoisomers of Cycloheximide

Analogous compounds related to cycloheximide (CHX, 1) have been investigated in the effort to reduce its high toxicity. Oritani's group reported the synthesis and antimicrobial activities of ten out of 16 (24) possible stereoisomers of cycloheximide (1) [5-7], including natural naramycin B (2) [8] and isocycloheximide (3) [9] (Fig. 1). The synthetic scheme was similar to that of 1 [10-12]. They prepared optically active anti- and syn-2,4-dimethylcyclohexanones by using microbial resolution originally developed by Oritani [13]. As shown in Scheme 1, racemic 1,2-cis-2,4-trans-2,4-dimethylcyclohexanol [(±)-4] was resolved to enantiomerically pure acetate (-)-5 and (+)-30 using culture broth of Bacillus subtilis var. niger in high yields [14]. The alcohol (-)-5 was oxidized to ketone 6 and this was coupled with aldehyde 7 [15]. Aldol reaction via Li-enolate afforded naramycin B (2) and (-)-(6S, aS)-1 as major products. On the other hand, four possible isomers were formed almost equally using Ti-enolate, but in

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