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

Enzyme??Mediated Synthesis of (S)??and (R)??Verapamil

E Brenna, C Fuganti, P Grasselli…

Index: Brenna, Elisabetta; Fuganti, Claudio; Grasselli, Piero; Serra, Stefano European Journal of Organic Chemistry, 2001 , # 7 p. 1349 - 1357

Full Text: HTML

Citation Number: 15

Abstract

Abstract A lipase-mediated synthesis of (S)-and (R)-verapamil is described. The key steps of the synthetic sequence are the enantioselective acetylation, mediated by Lipase PS, of allylic alcohol (Z)-(±)-2, affording the acetate derivative (Z, R)-(−)-3 (ee 92%) and the Ireland− Claisen rearrangement of this latter and of its enantiomer (Z, S)-(+)-3 (ee 92%) to afford acid derivatives (E, R)-(−)-4 (ee 94%) and (E, S)-(+)-4 (ee 93%), precursors of (S)- ...

veratraldehyde Structure

2-Bromopropane Structure

~74%

BENZYL ALCOHOL, 3,4-DIMETHOXY-alpha-ISOPROPYL- Structure

BENZYL ALCOHOL,...

N-Methylhomoveratrylamine Structure

N-Methylhomover...

N/A Structure

~92%

dexverapamil Structure

(2S)-(-)-2-(3,4-dimethoxyphenyl)-5-hydroxy-2-isopropylpentanenitrile Structure

(2S)-(-)-2-(3,4...

~%

dexverapamil Structure

(4S)-(-)-4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl acetate Structure

(4S)-(-)-4-cyan...

~%

dexverapamil Structure

(4E,3R)-(-)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enol Structure

(4E,3R)-(-)-3-(...

~%

dexverapamil Structure

(4E,3S)-(+)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enol Structure

(4E,3S)-(+)-3-(...

~%

dexverapamil Structure

(S,Z)-4-(3,4-dimethoxyphenyl)-5-methylhex-3-en-2-yl acetate Structure

(S,Z)-4-(3,4-di...

~%

dexverapamil Structure

(R,Z)-4-(3,4-dimethoxyphenyl)-5-methylhex-3-en-2-yl acetate Structure

(R,Z)-4-(3,4-di...

~%

dexverapamil Structure

(E,R)-(-)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enoic acid Structure

(E,R)-(-)-3-(3,...

~%

dexverapamil Structure

(E,S)-(+)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enoic acid Structure

(E,S)-(+)-3-(3,...

~%

dexverapamil Structure

methyl (4E,3R)-(-)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enoate Structure

methyl (4E,3R)-...

~%

dexverapamil Structure

methyl (4E,3S)-(+)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enoate Structure

methyl (4E,3S)-...

~%

dexverapamil Structure

(5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enenitrile Structure

(5E,4R)-(-)-4-(...

~%

dexverapamil Structure

(5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enenitrile Structure

(5E,4S)-(+)-4-(...

~%

dexverapamil Structure

(5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-en-1-ol Structure

(5E,4R)-(-)-4-(...

~%

dexverapamil Structure

(5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-en-1-ol Structure

(5E,4S)-(+)-4-(...

~%

dexverapamil Structure

methyl (5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enoate Structure

methyl (5E,4R)-...

~%

dexverapamil Structure

methyl (5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enoate Structure

methyl (5E,4S)-...

~%

dexverapamil Structure

(4S)-(-)-4-(3,4-dimethoxyphenyl)-4-formyl-5-methylhexyl acetate Structure

(4S)-(-)-4-(3,4...

~%

dexverapamil Structure

(4R)-(+)-4-(3,4-dimethoxyphenyl)-4-formyl-5-methylhexyl acetate Structure

(4R)-(+)-4-(3,4...

~%

dexverapamil Structure

(5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enoic acid Structure

(5E,4R)-(-)-4-(...

~%

dexverapamil Structure

(5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enoic acid Structure

(5E,4S)-(+)-4-(...

~%

dexverapamil Structure

(4R)-(+)-4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl acetate Structure

(4R)-(+)-4-cyan...

~%

dexverapamil Structure

(5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enyl acetate Structure

(5E,4R)-(-)-4-(...

~%

dexverapamil Structure

(5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enyl acetate Structure

(5E,4S)-(+)-4-(...

~%

dexverapamil Structure

(4E,3R)-(-)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enyl tosylate Structure

(4E,3R)-(-)-3-(...

~%

dexverapamil Structure

(4E,3S)-(+)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enyl tosylate Structure

(4E,3S)-(+)-3-(...

~%

dexverapamil Structure

N-Methylhomoveratrylamine Structure

N-Methylhomover...

N/A Structure

~93%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(2S)-(-)-2-(3,4-dimethoxyphenyl)-5-hydroxy-2-isopropylpentanenitrile Structure

(2S)-(-)-2-(3,4...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(4S)-(-)-4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl acetate Structure

(4S)-(-)-4-cyan...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(4E,3R)-(-)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enol Structure

(4E,3R)-(-)-3-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(4E,3S)-(+)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enol Structure

(4E,3S)-(+)-3-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(S,Z)-4-(3,4-dimethoxyphenyl)-5-methylhex-3-en-2-yl acetate Structure

(S,Z)-4-(3,4-di...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(R,Z)-4-(3,4-dimethoxyphenyl)-5-methylhex-3-en-2-yl acetate Structure

(R,Z)-4-(3,4-di...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(E,R)-(-)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enoic acid Structure

(E,R)-(-)-3-(3,...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(E,S)-(+)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enoic acid Structure

(E,S)-(+)-3-(3,...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

methyl (4E,3R)-(-)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enoate Structure

methyl (4E,3R)-...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

methyl (4E,3S)-(+)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enoate Structure

methyl (4E,3S)-...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enenitrile Structure

(5E,4R)-(-)-4-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enenitrile Structure

(5E,4S)-(+)-4-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-en-1-ol Structure

(5E,4R)-(-)-4-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-en-1-ol Structure

(5E,4S)-(+)-4-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

methyl (5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enoate Structure

methyl (5E,4R)-...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

methyl (5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enoate Structure

methyl (5E,4S)-...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(4S)-(-)-4-(3,4-dimethoxyphenyl)-4-formyl-5-methylhexyl acetate Structure

(4S)-(-)-4-(3,4...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(4R)-(+)-4-(3,4-dimethoxyphenyl)-4-formyl-5-methylhexyl acetate Structure

(4R)-(+)-4-(3,4...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enoic acid Structure

(5E,4R)-(-)-4-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enoic acid Structure

(5E,4S)-(+)-4-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(4R)-(+)-4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl acetate Structure

(4R)-(+)-4-cyan...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(5E,4R)-(-)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enyl acetate Structure

(5E,4R)-(-)-4-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(5E,4S)-(+)-4-(3,4-dimethoxyphenyl)-4-isopropylhept-5-enyl acetate Structure

(5E,4S)-(+)-4-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(4E,3R)-(-)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enyl tosylate Structure

(4E,3R)-(-)-3-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

(4E,3S)-(+)-3-(3,4-dimethoxyphenyl)-3-isopropylhex-4-enyl tosylate Structure

(4E,3S)-(+)-3-(...

~%

(S)-(-)-Verapamil Hydrochloride Structure

(S)-(-)-Verapam...

BENZYL ALCOHOL, 3,4-DIMETHOXY-alpha-ISOPROPYL- Structure

BENZYL ALCOHOL,...

~80%

1-Propanone,1-(3,4-dimethoxyphenyl)-2-methyl- Structure

1-Propanone,1-(...

veratraldehyde Structure

~%

1-Propanone,1-(3,4-dimethoxyphenyl)-2-methyl- Structure

1-Propanone,1-(...

Antifungal chalcones and new caffeic acid esters from Zuccag...

[Zacchino, Susana A.; Lopez, Silvia N.; Pezzenati, German D.; Furlan, Ricardo L.; Santecchia, Carina B.; Munoz, Lorena; Giannini, Fernando A.; Rodriguez, Ana M.; Enriz, Ricardo D. Journal of Natural Products, 1999 , vol. 62, # 10 p. 1353 - 1357]

254. Studies on the structure of emetine. Part III. Stabilit...

[Norcross; Openshaw Journal of the Chemical Society, 1949 , p. 1174,1178]