6164. Mevastatin

Nomenclature

CAS number: 73573-88-3
(2S)-2-Methylbutanoic acid (1S,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-7-methyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl ester; 7-[1,2,6,7,8,8a-hexahydro-2-methyl-8-(methylbutyryloxy)naphthyl]-3-hydroxyheptan-5-olide; 2β-methyl-8α-(2-methyl-1-oxobutoxy)mevinic acid lactone; compactin; 6-demethylmevinolin; CS-500; ML-236 B.
C23H34O5; mol wt 390.51.
C 70.74%, H 8.78%, O 20.49%.

Description and references

Fungal metabolite which is a potent inhibitor of HMG-CoA reductase, the rate controlling enzyme in cholesterol biosynthesis. Isoln from Penicillium citrinum: A. Endo et al., DE 2524355 corresp to US 3983140 (1975, 1976 to Sankyo). Isoln from P. brevicompactum, crystal and molecular structure: A. G. Brown et al., J. Chem. Soc. Perkin Trans. 1 1976, 1165. Inhibition of HMG-CoA reductase activity: A. Endo et al., FEBS Lett. 72, 323 (1976); M. S. Brown et al., J. Biol. Chem. 253, 1121 (1978). Therapeutic effects in primary hypercholesterolemia: A. Yamamoto et al., Atherosclerosis 35, 259 (1980). Total synthesis: N. Y. Wang et al., J. Am. Chem. Soc. 103, 6538 (1981); M. Hirama, M. Uei, ibid. 104, 4251 (1982); N. N. Girotra, N. L. Wendler, Tetrahedron Lett. 23, 5501 (1982); C.-T. Hsu et al., J. Am. Chem. Soc. 105, 593 (1983); P. A. Grieco et al., ibid. 1403; D. L. J. Clive et al., J. Am. Chem. Soc. 110, 6914 (1988). Review of syntheses: T. Rosen, C. H. Heathcock, Tetrahedron 42, 4909-4951 (1986). Review of mevastatin and related compounds: A. Endo, J. Med. Chem. 28, 401-405 (1985).

Chemical structure

Properties

Crystals from aq ethanol, mp 152°. [α]D22 +283° (c = 0.48 in acetone). uv max: 230, 237, 246 nm (log ε 4.28, 4.30, 4.11).