Cycloheximide

Title: Cycloheximide
CAS Registry Number: 66-81-9
CAS Name: 4-[(2R)-2-[(1S,3S,5S)-3,5-Dimethyl-2-oxocyclohexyl]-2-hydroxyethyl]-2,6-piperidinedione
Additional Names: 3-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]glutarimide; actidione; naramycin A
Manufacturers' Codes: NSC-185; U-4527
Molecular Formula: C15H23NO4
Molecular Weight: 281.35
Percent Composition: C 64.03%, H 8.24%, N 4.98%, O 22.75%
Literature References: Antibiotic substance isolated from the beers of streptomycin-producing strains of Streptomyces griseus: B. E. Leach et al., J. Am. Chem. Soc. 69, 474 (1947); J. H. Ford, B. E. Leach, ibid. 70, 1223 (1948); A. J. Whiffen et al., US 2574519 (1951 to Upjohn). Production, assay and antibiotic activity: A. J. Whiffen, J. Bacteriol. 56, 283 (1948). Improved production method: Kominek, US 3915802; US 3915803 (both 1975 to Upjohn). Structure: E. C. Kornfeld et al., J. Am. Chem. Soc. 71, 150 (1949). Absolute configuration: E. J. Eisenbraun et al., ibid. 80, 1261 (1958); F. Johnson, N. A. Starkovsky, Tetrahedron Lett. 1962, 1173; F. Johnson et al., J. Am. Chem. Soc. 87, 4612 (1965). Synthesis of dl- and l-forms: F. Johnson et al., ibid. 88, 149 (1966).
Properties: Plates from amyl acetate or water or 30% methanol, mp 119.5-121° (Whiffen, 1951); also reported as mp 115-116° (Johnson, 1966). [a]D29 -3.38° (c = 9.47 in methanol); [a]D25 +6.8° (c = 2 in H2O). Soly at 2°: water 2.1 g/100 ml, amyl acetate 7 g/100 ml. Also sol in chloroform, ether, acetone, methanol, ethanol, other common organic solvents except satd hydrocarbons. Relatively heat-stable, acid-stable, destroyed by boiling in aq soln at pH 7 for 1 hr, but shows no loss of activity after 15 min boiling. At pH 2 it is not destroyed by boiling for 1 hr. Rapidly inactivated at room temp by dil alkali with the formation of a volatile, fragrant ketone, 2,4-dimethylcyclohexanone. Extremely repellent to rats. LD50 i.v. in mice: 150 mg/kg (Leach).
Melting point: mp 119.5-121° (Whiffen, 1951); mp 115-116° (Johnson, 1966)
Optical Rotation: [a]D29 -3.38° (c = 9.47 in methanol); [a]D25 +6.8° (c = 2 in H2O)
Toxicity data: LD50 i.v. in mice: 150 mg/kg (Leach)
Derivative Type: Acetate
Molecular Formula: C17H25NO5
Molecular Weight: 323.38
Percent Composition: C 63.14%, H 7.79%, N 4.33%, O 24.74%
Properties: Glistening plates from methanol, mp 148-149°. [a]D25 +22° (c = 2.3 in methanol).
Melting point: mp 148-149°
Optical Rotation: [a]D25 +22° (c = 2.3 in methanol)
Use: Fungicide; plant growth regulator. As protein synthesis inhibitor.
Cyclohexyl Bromide Cyclohexyl Chloride Cyclohexylamine Cyclohexylcarbinol Cycloleucine

Cycloheximide
Cycloheximide
Identifiers
CAS number 66-81-9 YesY
PubChem 6197
ChemSpider 5962 YesY
UNII 98600C0908 YesY
KEGG C06685 N
ChEBI CHEBI:27641 YesY
ChEMBL CHEMBL123292 YesY
RTECS number MA4375000
Jmol-3D images Image 1
Properties
Molecular formula C15H23NO4
Molar mass 281.35 g/mol
Appearance colourless crystals
Melting point 119.5–121 °C
Hazards
MSDS Oxford MSDS
EU classification Toxic (T)
R-phrases R26 R27 R28
 N (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Cycloheximide is an inhibitor of protein biosynthesis in eukaryotic organisms, produced by the bacterium Streptomyces griseus. Cycloheximide exerts its effect by interfering with the translocation step in protein synthesis (movement of two tRNA molecules and mRNA in relation to the ribosome) thus blocking translational elongation. Cycloheximide is widely used in biomedical research to inhibit protein synthesis in eukaryotic cells studied in vitro (i.e. outside of organisms). It is inexpensive and works rapidly. Its effects are rapidly reversed by simply removing it from the culture medium.

Due to significant toxic side effects, including DNA damage, teratogenesis, and other reproductive effects (including birth defects and toxicity to sperm[1]), cycloheximide is generally used only in in vitro research applications, and is not suitable for human use as a therapeutic compound. Although it has been used as a fungicide in agricultural applications, this application is now decreasing as the health risks have become better understood.

Cycloheximide is degraded by alkali (pH > 7), decontamination of work surfaces and containers can be achieved by washing with a non-harmful alkali solution such as soap.

Since cycloheximide is an effective inhibitor of protein biosynthesis in eukaryotes only, it may be used to distinguish between proteins translated in the mitochondria and proteins translated in the cytosol. mRNA translated in cytosol or ER from mRNA derived from the nucleus will not be expressed in the presence of cycloheximide. Conversely, translation using mitochondrial ribosomes is unaffected by cycloheximide, and mitochondrial genes will continue to be expressed.