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

Synthesis of deuterium??labeled atorvastatin and its metabolites for use as internal standards in a LC/MS/MS method developed for quantitation of the drug and its …

…, MS Bednarz, JJ Hangeland, SZ Ahmed…

Index: Chen, Bang-Chi; Sundeen, Joseph E.; Guo, Peng; Bednarz, Mark S.; Hangeland, Jon J.; Ahmed, Syed Z.; Jemal, Mohammed Journal of Labelled Compounds and Radiopharmaceuticals, 2000 , vol. 43, # 3 p. 261 - 270

Full Text: HTML

Citation Number: 11

Abstract

Abstract D 5-labeled isotopomers of atorvastatin, atorvastatin lactone and its hydroxy metabolites were synthesized as internal standards for use in a LC/MS/MS method developed for the simultaneous quantitative determination of atorvastatin and its hydroxy metabolites in human serum. d 5-Atorvastatin and d 5-atorvastatin lactone were prepared from d 5-aniline whereas their corresponding hydroxy metabolites were synthesized using ...

2-Benzyloxy Atorvastatin-d5 Acetonide tert-Butyl Ester Structure

2-Benzyloxy Ato...

~81%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-4-[(2-hydroxyphenyl)carbamoyl]-3-(2,3,4,5,6-pentadeuteriophenyl)-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

2-(Benzyloxy)aniline Structure

2-(Benzyloxy)aniline

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-4-[(2-hydroxyphenyl)carbamoyl]-3-(2,3,4,5,6-pentadeuteriophenyl)-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

benzyl 2-nitrophenyl ether Structure

benzyl 2-nitrop...

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-4-[(2-hydroxyphenyl)carbamoyl]-3-(2,3,4,5,6-pentadeuteriophenyl)-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

N-2-BENZYLOXYPHENYL ISOBUTYRYLACETAMIDE Structure

N-2-BENZYLOXYPH...

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-4-[(2-hydroxyphenyl)carbamoyl]-3-(2,3,4,5,6-pentadeuteriophenyl)-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

N-2-Benzyloxyphenyl α-Benzilidene-d5 Isobutyrylacetamide Structure

N-2-Benzyloxyph...

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-4-[(2-hydroxyphenyl)carbamoyl]-3-(2,3,4,5,6-pentadeuteriophenyl)-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

2-[2-(4-fluorophenyl)-2-oxo-1-(2,3,4,5,6-pentadeuteriophenyl)ethyl]-4-methyl-3-oxo-N-(2-phenylmethoxyphenyl)pentanamide Structure

2-[2-(4-fluorop...

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-4-[(2-hydroxyphenyl)carbamoyl]-3-(2,3,4,5,6-pentadeuteriophenyl)-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

benzyl 2-nitrophenyl ether Structure

benzyl 2-nitrop...

~%

N-2-BENZYLOXYPHENYL ISOBUTYRYLACETAMIDE Structure

N-2-BENZYLOXYPH...

p-Benzyloxyaniline Structure

p-Benzyloxyaniline

~%

2-[2-(4-Fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic Acid, (4-Benzyloxy-phenyl)-amide Structure

2-[2-(4-Fluorop...

n-4-benzyloxyphenyl isobutyrylacetamide Structure

n-4-benzyloxyph...

~%

2-[2-(4-Fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic Acid, (4-Benzyloxy-phenyl)-amide Structure

2-[2-(4-Fluorop...

2-(Benzyloxy)aniline Structure

2-(Benzyloxy)aniline

~%

ortho-hydroxy atorvastatin Structure

ortho-hydroxy a...

benzyl 2-nitrophenyl ether Structure

benzyl 2-nitrop...

~%

ortho-hydroxy atorvastatin Structure

ortho-hydroxy a...

N-2-BENZYLOXYPHENYL ISOBUTYRYLACETAMIDE Structure

N-2-BENZYLOXYPH...

~%

ortho-hydroxy atorvastatin Structure

ortho-hydroxy a...

2-benzylidene-N-(2-(benzyloxy)phenyl)-4-methyl-3-oxopentanamide Structure

2-benzylidene-N...

~%

ortho-hydroxy atorvastatin Structure

ortho-hydroxy a...

2-[2-(4-Fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic Acid, (2-Benzyloxy-phenyl)-amide Structure

2-[2-(4-Fluorop...

~%

ortho-hydroxy atorvastatin Structure

ortho-hydroxy a...

(6-{2-[2-(4-Fluoro-phenyl)-4-(2-hydroxy-phenylcarbamoyl)-5-isopropyl-3-phenyl-pyrrol-1-yl]-ethyl}-2,2-dimethyl-[1,3]-dioxane-4-yl)-acetic Acid, tert-Butyl Ester Structure

(6-{2-[2-(4-Flu...

~%

ortho-hydroxy atorvastatin Structure

ortho-hydroxy a...

(2H5)Aniline Structure

~%

2-Methyl-2-propanyl [6-(2-{2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(2H5)phenylcarbamoyl]-1H-pyrrol-1-yl}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

2-Methyl-2-prop...

N-d5-phenyl isobutyrylacetamide Structure

N-d5-phenyl iso...

~%

2-Methyl-2-propanyl [6-(2-{2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(2H5)phenylcarbamoyl]-1H-pyrrol-1-yl}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

2-Methyl-2-prop...

N-4-Phenyl α-Benzylidene-d5 Isobutyrylacetamide Structure

N-4-Phenyl α-Be...

~%

2-Methyl-2-propanyl [6-(2-{2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(2H5)phenylcarbamoyl]-1H-pyrrol-1-yl}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

2-Methyl-2-prop...

tert-butyl 2-((4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate Structure

tert-butyl 2-((...

2-(2-(4-fluorophenyl)-2-oxo-1-phenylethyl)-4-methyl-3-oxo-N-(phenyl-d5)pentanamide Structure

2-(2-(4-fluorop...

~%

2-Methyl-2-propanyl [6-(2-{2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(2H5)phenylcarbamoyl]-1H-pyrrol-1-yl}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

2-Methyl-2-prop...

2-(Benzyloxy)aniline Structure

2-(Benzyloxy)aniline

~%

2-[2-(4-Fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic Acid, (2-Benzyloxy-phenyl)-amide Structure

2-[2-(4-Fluorop...

benzyl 2-nitrophenyl ether Structure

benzyl 2-nitrop...

~%

2-[2-(4-Fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic Acid, (2-Benzyloxy-phenyl)-amide Structure

2-[2-(4-Fluorop...

N-2-BENZYLOXYPHENYL ISOBUTYRYLACETAMIDE Structure

N-2-BENZYLOXYPH...

~%

2-[2-(4-Fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic Acid, (2-Benzyloxy-phenyl)-amide Structure

2-[2-(4-Fluorop...

4-Fluorobenzaldehyde Structure

4-Fluorobenzaldehyde

2-benzylidene-N-(2-(benzyloxy)phenyl)-4-methyl-3-oxopentanamide Structure

2-benzylidene-N...

~%

2-[2-(4-Fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic Acid, (2-Benzyloxy-phenyl)-amide Structure

2-[2-(4-Fluorop...

p-Benzyloxyaniline Structure

p-Benzyloxyaniline

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-3-phenyl-4-[(4-phenylmethoxyphenyl)carbamoyl]-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

n-4-benzyloxyphenyl isobutyrylacetamide Structure

n-4-benzyloxyph...

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-3-phenyl-4-[(4-phenylmethoxyphenyl)carbamoyl]-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

N-4-Benzyloxyphenyl α-Benzilidene Isobutyrylacetamide Structure

N-4-Benzyloxyph...

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-3-phenyl-4-[(4-phenylmethoxyphenyl)carbamoyl]-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

tert-butyl 2-((4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate Structure

tert-butyl 2-((...

2-[2-(4-Fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic Acid, (4-Benzyloxy-phenyl)-amide Structure

2-[2-(4-Fluorop...

~%

tert-butyl 2-[(4R,6R)-6-[2-[2-(4-fluorophenyl)-3-phenyl-4-[(4-phenylmethoxyphenyl)carbamoyl]-5-propan-2-ylpyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Structure

tert-butyl 2-[(...

(2H5)Aniline Structure

~%

N-4-Phenyl α-Benzylidene-d5 Isobutyrylacetamide Structure

N-4-Phenyl α-Be...

Benzaldehyde Structure

N-d5-phenyl isobutyrylacetamide Structure

N-d5-phenyl iso...

~%

N-4-Phenyl α-Benzylidene-d5 Isobutyrylacetamide Structure

N-4-Phenyl α-Be...