Glutarimide antibiotics

That the methyl group in the less substituted isomer of the enamine (20) is axial was borne out by the work of Johnson et al. (18) in the total synthesis of the glutarimide antibiotic //-dehydrocycloheximide (24). The acylation of the morpholine enamine of 2,4-dimethylcyclohexanone (25) with 3-glutarimidylacetylchloride (26), followed by the hydrolysis of the intermediate product (27) with an acid buffer, led to the desired product in 35 % yield. The formation of the product in a rather low yield could most probably be ascribed to the relatively low enamine-type aetivity exhibited by the tetrasubstituted isomer, which fails to undergo the acylation reaction, and also because in trisubstituted isomer one of the CHj groups is axial. Since the methyl groups in the product are trans to each other, the allylic methyl group in the less substituted isomer of the enamine should then be in the axial orientation. 

Obrig, T. G., Culp, W. J., McKeehan, W. L., and Hardesty, B. (1971). The mechanism by which cycloheximide and related glutarimide antibiotics inhibit peptide synthesis on reticulocyte ribosomes. J. Biol. Chem. 246, 174-181. 

Reaction of the nitrile oxide (498) with the enone (499) gave after chromatography the expected isoxazoline (500) plus some of its dehydro derivative (76TL3983). Hydrogenation of (500) using 30% Pd/SrC03 as catalyst yielded an enaminoketone (501) which was further hydrolyzed to the diketone (502 Scheme 110). This compound is a gem-dimethyl isomer of dehydrocycloheximide, a key intermediate in a previously reported synthesis of the glutarimide antibiotic cycloheximide. 

The GLUTARIMIDE antibiotic streptimidone is formed from seven malonate units and is in itself unusual by having the polyketide synthesis initiated by a malonate unit which is retained intact in the final structure. The derivitive, 9-methylstreptimidone (12) is reported to be made similarly, with a double decarboxylation of the terminal malonate unit. This is... 

Oxo-3a,4,5,6,7,7a-hexahydroindoxazenes (92) are oxidized by chloranil to the 4,5,6,7-tetrahydro derivatives and are useful precursors for the synthesis of 2-acylcyclohexane-l,3-diones and for glutarimide antibiotic analogs.105... 

The sixth chapter Synthetic Studies on Heterocyclic Antibiotics Containing Nitrogen Atoms by Hiromasa Kiyota presents a very comprehensive review on a variety of heterocyclic antibiotics and phytotoxins. Early and recent examples of synthetic studies of glutarimide antibiotics, antimycins, and tabtoxins and related bioactive heterocycles based on the works of his group are retrospectively reviewed. The content is believed to attracts much interest of synthetic chemists as well as heterocyclic chemists and researchers in life science fields. 

Hostalek, Z., Blumauerova, M., Vanek, Z. Tetracycline antibiotics. In Secondary Products of Metabolism (A. H. Rose, ed.), pp. 293-354. Academic Press, London 1979 Johnson, F. Chemistry of glutarimide antibiotics. Prog. Chem. Org. Natl. Prod. 29, 140-202 (1971)... 

Starkovsky, N. a., and F. Johnson Glutarimide antibiotics. Part V. The absolute configuration of the side-chain asymmetric center of cycloheximide. Tetrahedron Letters, 919 (1964). 

Umezawa, H. Glutarimide antibiotics. Recent advances in chemistry and biochemistry of antibiotics, p. 40. Microbial Chemistry Research Foundation, Tokyo 1964. Vanek, Z., M. Puza, J. Cudlin, and L. DolezilovA Metabolites of Streptomyces noursei. III. Incorporation of C-carbon dioxide into cycloheximide. Biochem. Biophys. Research Commun. 17, 532 (1964). 

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