Ono H

low yields. Scheme 2 shows the preparation of isocycloheximide (3) and its isomers. Asymmetric hydrolysis of racemic acetate (±)-8 gave (-)-acetate [(—)—10] with 92% ee [16]. Optical purity of (-)-10 was enriched by recrys-tallization of the corresponding DNB ester, and oxidation gave pure ketone (+)-11. Aldol reaction provided natural 3, neocycloheximide 12 [11] and a-epiisocycloheximide 13 [17]. The enantiomers of these three compounds were prepared similarly [7]. Antimicrobial assays against a yeast Saccharomyces cerevisiae and the rice blast disease fungus Pyricularia oryzae revealed that 1, 2, and ent-13 (4-epi-1) showed strong growth inhibitory activity.

In addition, they prepared racemic steroisomers of des-methyl analogs of 1 (14 to 17, Fig. 2). As a result, only 4-desmethylcycloheximide (±)-15 with the natural relative stereochemistry of CHX showed weak activity against S. cerevisiae and Aspergillus niger and Cochliobolus miyabeanus [18]. Consequently, 4S, a^-configuration is at least responsible for the CHX activity.

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