121009-77-6

Basic information

• Product Name: simvastatin acid
• Synonyms: simvastatin acid;(3R,5R)-3,5-Dihydroxy-7-[(1S)-1-(2,2-dimethylbutyryloxy)-3β,7α-dimethyl-1,2,3,7,8,8aα-hexahydronaphthalene-8α-yl]heptanoic acid;(βR,δR,1S)-8α-(2,2-Dimethyl-1-oxobutoxy)-1,2,6,7,8,8aβ-hexahydro-β,δ-dihydroxy-2β,6α-dimethyl-1β-naphthaleneheptanoic acid;2,2-Dimethylbutanoic acid [(1S)-1,2,3,7,8,8aα-hexahydro-3β,7α-dimethyl-8α-[(3R,5R)-3,5-dihydroxy-6-carboxyhexyl]naphthalen]-1β-yl ester;2,2-Dimethylbutyric acid (1S)-3β,7α-dimethyl-8α-[(3R,5R)-3,5-dihydroxy-6-carboxyhexyl]-1,2,3,7,8,8aα-hexahydronaphthalene-1β-yl ester;Simvastatin hydroxy acid;(3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-(2,2-dimethylbutanoyloxy)-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid
• CAS NO: 121009-77-6
• Molecular Formula: C₂₅H₄₀O₆
• Molecular Weight: 436.585
• Mol File: 121009-77-6.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 607°Cat760mmHg
• Flash Point: 198.2°C
• Appearance: /
• Density: 1.13g/cm³
• Vapor Pressure: 2.89E-17mmHg at 25°C
• Refractive Index: 1.536
• PKA: 4.31±0.10(Predicted)
• CAS DataBase Reference: simvastatin acid(CAS DataBase Reference)
• NIST Chemistry Reference: simvastatin acid(121009-77-6)
• EPA Substance Registry System: simvastatin acid(121009-77-6)

Safety Data

• Hazardous Substances Data: 121009-77-6(Hazardous Substances Data)

Usage

InChI:InChI=1/C25H40O6/c1-6-25(4,5)24(30)31-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-18(26)13-19(27)14-22(28)29/h7-8,11,15-16,18-21,23,26-27H,6,9-10,12-14H2,1-5H3,(H,28,29)/t15-,16-,18+,19+,20-,21-,23-/m0/s1

Upstream product

• 123049-81-0 simvastatin 
• 145576-25-6 simvastatin acetate 
• 851402-85-2 bis-simvastatin 
• 139893-43-9 simvastatin ammonium salt 
• 74-88-4 methyl iodide 
• 134970-33-5 N-butyl-7-<1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-<<2,2-dimethylbutanoyl>oxy>-1(S)-naphthyl>-3(R),5(R)-dihydroxyheptanoic acid amide 
• 938063-63-9 methyl 3-[(2,2-dimethyl-1-oxobutyl)thio]propionate 
• 132748-10-8 (3R,5R)-3,5-dihydroxy-7-((1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)heptanoic acid 
• 75330-75-5 lovastatin 

Downstream Products

• 476305-24-5 C₅₀H₇₆O₁₀ 
• 139893-43-9 simvastatin ammonium salt 
• 123049-81-0 simvastatin 

Relevant articles and documents

Method for synthesizing simvastatin impurity D

The invention provides a method for synthesizing a simvastatin impurity D. The method comprises the following steps: by taking easily available raw material medicine simvastatin as an initial raw material, firstly carrying out ring opening on lactone, then protecting two hydroxyl groups in a molecule by using acetonylidene, and condensing an obtained intermediate with another molecule raw material medicine simvastatin, and finally, removing the protecting group acetone by using hydrochloric acid to obtain the simvastatin impurity D. According to the method, the simvastatin which is cheap and easy to obtain is taken as a starting raw material, a final target product is obtained through four-step reaction, the whole reaction route is simple and economical, and has very high practical value, and a relatively large amount of preparation can be carried out for guiding production; meanwhile, the blank of no report about the synthesis method of the compound up to now is filled.

Lipophilic statins inhibit growth and reduce invasiveness of human endometrial stromal cells

Purpose: To compare effects of lipid-soluble statins (simvastatin, lovastatin, atorvastatin) and water-soluble statin (pravastatin) on growth and invasiveness of human endometrial stromal (HES) cells. Methods: Endometrial biopsies were collected during the proliferative phase from five volunteers. HES cells were isolated and cultured in the absence or in the presence of simvastatin, lovastatin, atorvastatin, and pravastatin. Effects of statins on DNA synthesis, cell viability, activity of caspases 3/7 and invasiveness were evaluated. Results: The proliferation of HES cells was significantly decreased by simvastatin (by 47–89%), lovastatin (by 46–78%), and atorvastatin (by 21–48%) in a concentration-dependent manner. Activity of executioner caspases 3/7 was significantly increased by simvastatin (by 10–25%), lovastatin (by 19%) and atorvastatin (by 7–10%) in a concentration-dependent manner. The greatest effects were observed in response to simvastatin. Accounting for the effects of statins on cell number, the invasiveness of HES cells was significantly decreased in cells treated with simvastatin (by 49%), lovastatin (by 54%), and atorvastatin (by 53%). Pravastatin had little or no effects on any of the tested endpoints. Conclusions: Present findings demonstrate that only lipid-soluble among tested statins were effective in inhibition of growth and invasiveness of HES cells. These findings may have clinical relevance in treatment of endometriosis.

Directed Evolution and Structural Characterization of a Simvastatin Synthase

Enzymes from natural product biosynthetic pathways are attractive candidates for creating tailored biocatalysts to produce semisynthetic pharmaceutical compounds. LovD is an acyltransferase that converts the inactive monacolin J acid (MJA) into the cholesterol-lowering lovastatin. LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic α-dimethylbutyryl thioester, albeit with suboptimal properties as a biocatalyst. Here we used directed evolution to improve the properties of LovD toward semisynthesis of simvastatin. Mutants with improved catalytic efficiency, solubility, and thermal stability were obtained, with the best mutant displaying an ～11-fold increase in an Escherichia coli-based biocatalytic platform. To understand the structural basis of LovD enzymology, seven X-ray crystal structures were determined, including the parent LovD, an improved mutant G5, and G5 cocrystallized with ligands. Comparisons between the structures reveal that beneficial mutations stabilize the structure of G5 in a more compact conformation that is favorable for catalysis.