160204-82-0

Upstream product

• 139993-90-1 4-(4-Fluorophenyl)-3-formyl-2-isopropyl-5-methyl-1-methylsulfonylpyrrole 
• 147118-35-2 methyl (3R)-3-(tert-butyldimethylsilyloxy)-5-oxo-6-triphenylphosphoranylidenehexanoate 
• 358-23-6 trifluoromethylsulfonic anhydride 
• 205647-15-0 (3R)-[(tert-butyldimethylsilyl)oxy]-7-[4-(4-fluorophenyl)-2-isopropyl-5-methyl-1H-pyrrol-3-yl]-5-oxo-6-heptenoic acid methyl ester 
• 322-30-5 2-amino-1-(4-fluorophenyl)-1-propanone hydrochloride 
• 7152-15-0 ethyl 4-methyl-3-oxo-pentanoate 
• 188557-35-9 4-(4-Fluoro-phenyl)-2-isopropyl-5-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 
• 188557-36-0 4-(4-Fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-5-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 
• 188557-37-1 [4-(4-Fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-5-methyl-1H-pyrrol-3-yl]-methanol 
• 148866-38-0 (4R)-[(tert-butyldimethylsilyl)oxy]-6-[(methanesulfinyl)methylene]tetrahydropyran-2-one 
• 109721-08-6 (S)-3-<(tert-butyldimethylsilyl)oxy>pentanedioic acid, monomethylester 
• 205647-21-8 (3R)-[(tert-butyldimethylsilyl)oxy]-7-[4-(4-fluorophenyl)-2-isopropyl-5-methyl-1H-pyrrol-3-yl]-6-(methanesulfinyl)-5-oxoheptanoic acid methyl ester 
• 205647-16-1 (3R)-[(tert-butyldimethylsilyl)oxy]-6-(methanesulfinyl)-5-oxohexanoic acid 
• 205647-18-3 [[4-(4-fluorophenyl)-2-isopropyl-5-methyl-1H-pyrrol-3-yl]methyl]dimethylamine 

Downstream Products

• 188557-38-2 (E)-(R)-7-[4-(4-Fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-5-methyl-1H-pyrrol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester 
• 148966-79-4 (3R,5S)-7-[4-(4-fluorophenyl)-2-isopropyl-1-(methanesulfonyl)-5-methyl-1H-pyrrol-3-yl]-3,5-dihydroxy-6-heptenoic acid methyl ester 

Relevant academic research and scientific papers

Optical resolution of 3-(silyloxy)glutaric acid half esters and their utilization for enantioconvergent synthesis of a HMG-CoA reductase inhibitor

Useful chiral synthons, (3R)- and (3S)-[(tert- butyldimethylsilyl)oxy]pentanedioic acid monomethyl ester, (R)-1 and (S)-1, were obtained by optical resolution of a racemic mixture of 1. Sulfoxide 8 has been developed from (S)-1 as a new building block for preparing HMG-CoA reductase inhibitors. Two alternate chiral synthons 2 and 8, synthesized from (R)-1 and (S)-1, respectively, were employed for enantioconvergent synthesis of potent inhibitor 15 containing a pyrrole moiety.

Synthesis and biological activity of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates, a novel series of HMG-CoA reductase inhibitors

A novel series of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates were synthesized and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Monocalcium bis(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N- methanesulfonylaminopyrimidin)-5-yl]-(3R,5S)-dihydroxy- (E)-6-heptenoate (3a, S-4522) was selected as a candidate for further evaluation. Compound 3a was approximately four times more potent than lovastatin sodium salt (in inhibiting HMG-CoA reductase in vitro (IC50 = 11 nM). Compound 3a was shown to be the most potent cholesterol biosynthesis inhibitor in this series (IC50 = 1.12 nM) in rat isolated hepatocytes; its inhibitory activity was approximately 100 times more potent than pravastatin.

Practical synthesis of chiral synthons for the preparation of HMG-CoA reductase inhibitors

A practical procedure for the enantioselective preparation of optically pure (R)- and (S)-monomethyl esters of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic acid has been developed by diastereoselective ring-opening of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic anhydride 5 by benzyl (R)- and (S)-mandelate, respectively. These half-esters afforded chiral Wittig reagent 2 and Horner-Wadsworth-Emmons (HWE) reagent 1 efficiently which have been proved to be useful in the synthesis of HMG-CoA reductase inhibitors. The method is applied to the synthesis of the (R)-3-methylglutaric acid, monomethyl ester.