e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

A novel and practical synthesis of the 6. alpha.-hydroxymethyl metabolite of simvastatin

TJ Lee, WF Hoffman, WJ Holtz…

Index: Journal of Organic Chemistry, , vol. 57, # 7 p. 1966 - 1968

Full Text: HTML

Citation Number: 5

Abstract

... This material is contained in many libraries on microfiche, immediately follows this article in the microfikn version of the journal, and can be ... Ta-Jyh Lee,* William F. Hoffman, Wilbur J. Holtz, and Robert L. Smith Department of Medicinal Chemistry, Merck Sharp & Dohme ... J. Org. ...

4a',6'-Anhydro-4-tert-butyldimethylsilyl Simvastatin Structure

4a',6'-Anhydro-...

~58%

N/A Structure

6'-HYDROXYMETHYL SIMVASTATIN Structure

6'-HYDROXYMETHY...

Simvastatin Structure

~%

6'-HYDROXYMETHYL SIMVASTATIN Structure

6'-HYDROXYMETHY...

6(R)-[2-[8(S)-((2,2-Dimethylbutyryl)oxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphth-1(S)-yl]ethyl]-4(R)-((tert-butyldimethylsilyl)oxy)-3,4,5,6-tetrahydro-2H-pyran-2-one Structure

6(R)-[2-[8(S)-(...

~%

6'-HYDROXYMETHYL SIMVASTATIN Structure

6'-HYDROXYMETHY...

(1aR,3R,4R,4aS,5S,7R,8aR)-4-(2-((2R,4R)-4-((tert-butyldimethylsilyl)oxy)-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-2-iodo-3,7-dimethyloctahydro-3H-naphtho[1,8a-b]oxiren-5-yl 2,2-dimethylbutanoate Structure

(1aR,3R,4R,4aS,...

~%

6'-HYDROXYMETHYL SIMVASTATIN Structure

6'-HYDROXYMETHY...

[(1S,3R,4S,4aS,7S,8S,8aS)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-4-chloro-4a-hydroxy-3,7-dimethyl-2,3,4,7,8,8a-hexahydro-1H-naphthalen-1-yl] 2,2-dimethylbutanoate Structure

[(1S,3R,4S,4aS,...

~%

6'-HYDROXYMETHYL SIMVASTATIN Structure

6'-HYDROXYMETHY...

Simvastatin Structure

~%

[(1S,3R,4S,4aS,7S,8S,8aS)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-4-chloro-4a-hydroxy-3,7-dimethyl-2,3,4,7,8,8a-hexahydro-1H-naphthalen-1-yl] 2,2-dimethylbutanoate Structure

[(1S,3R,4S,4aS,...

tert-Butyldimethylsilyl chloride Structure

tert-Butyldimet...

~%

[(1S,3R,4S,4aS,7S,8S,8aS)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-4-chloro-4a-hydroxy-3,7-dimethyl-2,3,4,7,8,8a-hexahydro-1H-naphthalen-1-yl] 2,2-dimethylbutanoate Structure

[(1S,3R,4S,4aS,...

6(R)-[2-[8(S)-((2,2-Dimethylbutyryl)oxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphth-1(S)-yl]ethyl]-4(R)-((tert-butyldimethylsilyl)oxy)-3,4,5,6-tetrahydro-2H-pyran-2-one Structure

6(R)-[2-[8(S)-(...

~%

[(1S,3R,4S,4aS,7S,8S,8aS)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-4-chloro-4a-hydroxy-3,7-dimethyl-2,3,4,7,8,8a-hexahydro-1H-naphthalen-1-yl] 2,2-dimethylbutanoate Structure

[(1S,3R,4S,4aS,...

(1aR,3R,4R,4aS,5S,7R,8aR)-4-(2-((2R,4R)-4-((tert-butyldimethylsilyl)oxy)-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-2-iodo-3,7-dimethyloctahydro-3H-naphtho[1,8a-b]oxiren-5-yl 2,2-dimethylbutanoate Structure

(1aR,3R,4R,4aS,...

~%

4a',6'-Anhydro-4-tert-butyldimethylsilyl Simvastatin Structure

4a',6'-Anhydro-...

Simvastatin Structure

~%

4a',6'-Anhydro-4-tert-butyldimethylsilyl Simvastatin Structure

4a',6'-Anhydro-...

tert-Butyldimethylsilyl chloride Structure

tert-Butyldimet...

~%

4a',6'-Anhydro-4-tert-butyldimethylsilyl Simvastatin Structure

4a',6'-Anhydro-...

6(R)-[2-[8(S)-((2,2-Dimethylbutyryl)oxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphth-1(S)-yl]ethyl]-4(R)-((tert-butyldimethylsilyl)oxy)-3,4,5,6-tetrahydro-2H-pyran-2-one Structure

6(R)-[2-[8(S)-(...

~%

4a',6'-Anhydro-4-tert-butyldimethylsilyl Simvastatin Structure

4a',6'-Anhydro-...

[(1S,3R,4S,4aS,7S,8S,8aS)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-4-chloro-4a-hydroxy-3,7-dimethyl-2,3,4,7,8,8a-hexahydro-1H-naphthalen-1-yl] 2,2-dimethylbutanoate Structure

[(1S,3R,4S,4aS,...

~%

4a',6'-Anhydro-4-tert-butyldimethylsilyl Simvastatin Structure

4a',6'-Anhydro-...