Lovastatin Raw Materials Lovastatin Powder

CAS:75330-75-5

MF:C24H36O5

MW:404.54

EINECS:616-212-7

Specification​: 99% min Lovastatin Powder

Sample:Lovastatin Powder

Packaging:1kg/bag, 25kg/drum

Brand: Henrikang

Appearance: White to Off-White

Storage: Cool Dry Place

Shelf Life: 2 Years

Test Method: HPLC

Lovastatin Powder Usage and Synthesis.

Lovastatin is a hexahydronaphthalene ester isolated from Aspergillus terreus culture broth, an inactive lactone that is hydrolysed after oral administration to become active, and has a strong competitive inhibitory effect on HMG-CoA reductase in the liver.

HMG-CoA reductase is the rate-limiting enzyme for the de novo synthesis of cholesterol in vivo. Inhibition of this enzyme blocks the conversion of HMG-CoA to methylglutarate, resulting in a marked reduction in cholesterol synthesis, causing enhanced hepatic expression of the LDL receptor, and enhanced clearance of plasma LDL-C.

Reduced cholesterol synthesis can also reduce hepatic synthesis of ApoB100, thus reducing VLDL synthesis.

Clinical observation shows that this product has good effect of lowering plasma total cholesterol and LDLC regardless of various causes of hypercholesterolaemia such as heterozygous familial hypercholesterolaemia, polygenic hypercholesterolaemia, diabetes mellitus or nephrotic syndrome.

Uses of Lovastatin.

Used for heterozygous familial, non-familial, secondary hyperlipidaemia of all types, i.e. diabetes mellitus and nephrotic syndrome secondary to hypercholesterolaemia.

It reduces TC, LF, LDL-C and raises HDL-C, reducing the risk of myocardial infarction, unstable angina and the need for coronary angioplasty.

New lipid regulator-HMG-CoA (β-hydroxy, β-methyl-glutarate monoacyl coenzyme A) reductase inhibitor.

It can significantly reduce the concentration of serum total cholesterol, which is hydrolysed to the corresponding β-hydroxy acid, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and inhibit cholesterol synthesis after oral administration.

It is clinically used for heterozygous familial hypercholesterolaemia, severe and mild primary hypercholesterolaemia, and can also be used as an adjunct to dietary therapy to reduce excessive cholesterol and LDL cholesterol levels.

Cholesterol-lowering drug and competitive inhibitor of HMG-CoA reductase, a rate-limiting enzyme for cholesterol synthesis.

Blocks the production of mevalonate, a key compound in cholesterol and isoprene production. This product is a substrate for Pgp and CYP3A. It increases cellular resistance to anticancer drugs, such as Adriamycin, and induces apoptosis in myeloma cells.

This product induces apoptosis in numerous cancer cells, in part by inhibiting Rho family GTPases. It causes the cell cycle to be captured in the G1 and G2/M phases.

Synthetics of Lovastatin.

Acetic acid and malonic acid are condensed, reduced and dehydrated to form diketide intermediates, a process catalysed by keto reductase (KR), enol reductase (ER) or methyltransferase (MeT), which is repeated to form hexaketide, which is then subjected to the enzyme-promoted Diels-Alder reaction to produce the bicyclic naphthalenide (decorin) backbone. Next, the enzymatic Diels-Alder reaction produces a bicyclic naphthalene (decalin) skeleton, and this bicyclic adduct extends to nonaketide, which is released from polyketide synthase (PKS) to form 4a,5-dihydromonacolin L. 4a,5-dihydromonacolin L is converted to 3α-hydroxy-3,5-dihydromonacolin L, which is spontaneously dehydrogenated in the presence of molecular oxygen, to monacolin L, which is spontaneously dehydrogenated in the presence of molecular oxygen. In the presence of molecular oxygen, monacolin L was hydroxylated to monacolin J at C-8, and the enzyme involved in this reaction was proved to be monooxygenase by inhibition tests with methylpyrazone, carbon monoxide, and sulfhydryl reagents.

Monacolin J is esterified to lovastatin via (2R)-methylbutyrate.

Production Method of Lovastatin.

Lovastatin is obtained by fermentation. The available strains are: (i) Monescusruber; (ii) Monescuspurpureus; (iii) Monescuspilosus; (iv) Aspergillusterreus; (v) PenicilliumCitrunum.

When Monescusruber was used as the strain, the culture solution was: 6% glucose, 2.5% peptone, 0.5% corn syrup, and 0.5% ammonium chloride. The strain was incubated together with the culture solution for 10d at 28°C under aerobic conditions.

5L of filtrate was filtered and extracted with 5LPh of ethyl acetate of value 3. The extract was concentrated to dryness in vacuum and the residue was dissolved in 100 ml of benzene. The insoluble material was removed by filtration and the filtrate was washed twice with 100ml of 5% aqueous sodium carbonate solution, then stirred with 100ml of 0.2 mol/L sodium hydroxide solution for 2h at room temperature.

The aqueous layer was collected and adjusted to Ph=3 with 6 mol/L hydrochloric acid and then extracted twice with 100 ml ethyl acetate.

The extracts were combined and evaporated to dryness to give 260 mg of oil.

The oil was dissolved in a small amount of benzene and the resulting crystals were recrystallised with a mixture of acetone and water to give 87 mg of colourless lovastatin crystals with a melting point of 157-159°C (decomposition) and [α]D23+307.6° (C=1, methanol).