[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of lovastatin (350 g, 0.865 mmol), phenylboronic acid (110.8 g, 0.909 mmol) and toluene (1.75 L) was heated with agitation under a nitrogen atmosphere. A reflux temperature of 100-105° C. was maintained for 55 minutes as water was collected and separated from the reaction mixture. The solution was cooled and 1.39 L of toluene was removed by vacuum distillation at 40-50° C. The concentrated solution was treated with hexanes (3.15 L) between 40-50° C. The resulting suspension was cooled to 0-5° C. for 2 hours and the product was filtered and washed with 0-5° C. hexanes (350 mL). The product was dried at 35-40° C. under vacuum to provide 427.9 g (37%) of lovastatin phenylboronate at >99% purity by HPLC. was heated with agitation under a nitrogen atmosphere was collected separated from the reaction mixture The solution was cooled 1.39 L of toluene was removed by vacuum distillation at 40-50° C The concentrated solution was treated with hexanes (3.15 L) between 40-50° C the product was filtered washed with 0-5° C. hexanes (350 mL) The product was dried at 35-40° C. under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: simvastatin (Zocor); pravastatin (Pravachol); fluvasatin (Lescol).

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of Lovastatin (50 g, 0.124 mol) and benzylamine (46.32 g, 0.432 mol) was mixed with toluene (25 ml) and heated to 80° C. under nitrogen atmosphere for 1 hour. Absence of Lovastatin was monitored by HPLC. Excess benzylamine and toluene were distilled off at 85-90° C. under reduced pressure (5-10 mm Hg). The residue was mixed with xylenes (50 ml) and distilled again at 85-90° C. under reduced pressure (5-10 mm Hg) to get product, lovastatin benzylamide, as light brown viscous liquid. Yield: 67.5 g. Excess benzylamine and toluene were distilled off at 85-90° C. under reduced pressure (5-10 mm Hg) The residue was mixed with xylenes (50 ml) distilled again at 85-90° C. under reduced pressure (5-10 mm Hg)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of Lovastatin (50 g, 0.124 mol) and benzylamine (46.32 g, 0.432 mol) was mixed with toluene (25 ml) and heated to 80° C. under nitrogen atmosphere for 1 hour. Absence of Lovastatin was monitored by HPLC. Excess benzylamine and toluene were distilled off at 85-90° C. under reduced pressure (5-10 mm Hg). The residue was mixed with xylenes (50 ml) and distilled again at 85-90° C. under reduced pressure (5-10 mm Hg) to get product, lovastatin benzylamide, as light brown viscous liquid. Yield: 67.5 g. Excess benzylamine and toluene were distilled off at 85-90° C. under reduced pressure (5-10 mm Hg) The residue was mixed with xylenes (50 ml) distilled again at 85-90° C. under reduced pressure (5-10 mm Hg)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4.0 g (10 mmol) mevinolin in 20 ml pyridine at room temperature are added 20 ml acetic acid anhydride. After 1 h the reaction mixture is concentrated in-vacuo. The residue is dissolved with 10 ml methyl-t-butyl ether and washed successively with water, 0.1 N HCl and brine. The organic phase is then dried over sodium sulfate and the solvent removed in vacuo. The crude product is purified by silica gel chromatography (methyl-t-butyl ether 1/3) to afford 2-methyl-butyric acid 3,7-dimethyl-8-[2-(6-oxo-3,6-dihydro-2H-pyran-2-yl)-ethyl]-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester) as a white powder. After 1 h the reaction mixture is concentrated in-vacuo The residue is dissolved with 10 ml methyl-t-butyl ether washed successively with water, 0.1 N HCl and brine The organic phase is then dried over sodium sulfate the solvent removed in vacuo The crude product is purified by silica gel chromatography (methyl-t-butyl ether 1/3)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.13 g (0.32 mmol) of mevinolin in 15 ml of THF are added 0.5 ml (5 mmol) benzylamine. The stirred reaction mixture is heated at reflux for 7 hours. After cooling to room temperature the reaction is diluted with 20 ml of methyl-t-butyl ether and washed successively with 0.1 N HCl and brine. The organic phase is then dried over sodium sulfate and the solvent evaporated. The crude product is purified by silica gel chromatography (ethyl acetate) to afford the desired product as an oil. The stirred reaction mixture is heated at reflux for 7 hours washed successively with 0.1 N HCl and brine The organic phase is then dried over sodium sulfate the solvent evaporated The crude product is purified by silica gel chromatography (ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 65 mg (0.15 mmol) of mevinolin in 5 ml of ethanol are added 22 mg (1.0 mmol) lithium borohydride and the resulting mixture is stirred overnight at room temperature. The reaction is quenched with 0.1 N aqueous HCl. The phases are separated and the aqueous phase is extracted twice with ethyl acetate. The organic phases are combined, washed with brine and dried over sodium sulfate. The solvent is evaporated and the crude product purified by silica gel chromatography (ethyl acetate) to afford 2-methyl-butyric acid 3,7-dimethyl-8-(3,5,7-trihydroxy-heptyl)-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester as an oil. The reaction is quenched with 0.1 N aqueous HCl The phases are separated the aqueous phase is extracted twice with ethyl acetate washed with brine dried over sodium sulfate The solvent is evaporated the crude product purified by silica gel chromatography (ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After 15 minutes, 202 mg (0.50 mmol) of mevinolin are added and the reaction mixture is kept at −77° C. for 30 minutes. Then 171 mg (1.0 mmol) benzyl bromide are added. After 2 hours the reaction is let come to room temperature and poured onto 0.1 N aqueous HCl. The phases are separated and the aqueous phase is extracted twice with ethyl acetate. The organic phases are combined, washed with brine and dried over sodium sulfate. The solvent is evaporated and the crude product is purified by silica gel chromatography (diethyl ether/hexane 2/1) to afford the desired product as a colorless oil. the reaction mixture is kept at −77° C. for 30 minutes After 2 hours the reaction is let come to room temperature The phases are separated the aqueous phase is extracted twice with ethyl acetate washed with brine dried over sodium sulfate The solvent is evaporated the crude product is purified by silica gel chromatography (diethyl ether/hexane 2/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: statins, for example atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin;

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: statins, for example atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin;

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lovastatin shows poor solubility under the aqueous conditions necessary for enzymatic activity. Alternatively, in one aspect, a suspension of lovastatin in water is raised to pH>12 to effect a rapid hydrolysis of the lactone ring resulting in the in-situ formation of the more soluble lovastatin acid salt. In practice, a suspension of lovastatin in water/MeOH is treated with a solution of 1 mole equivalent of NaOH in water and stirred until dissolution is complete. The pH of the reaction mixture is then readjusted to a range suitable for the enzymatic reaction and the enzyme is added. is raised to pH>12 a rapid hydrolysis of the lactone ring

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lovastatin is chemically represented as [1S-[1α(R*),3α,7β,8β(2S*,4S*),8αβ]]-2-methylbutanoic acid 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester, and strains producing the compound also produce an acid form of lovastatin, i.e., mevinolinic acid, which is converted into lovastatin(mevinolin) as a lactone form in the course of isolation and recovery. producing the compound