Lipase-catalyzed kinetic resolution of 1,2,3,4-tetrahydroisoquinoline-1-acetic acid esters

The enantiomers of 1,2,3,4-tetrahydroisoquinoline- and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-acetic acids were prepared via Burkholderia cepacia lipase (lipase PS-D)-catalyzed kinetic resolution of the corresponding ethyl and 2-methoxyethyl esters using enantioselective (E > 200) hydrolysis in DIPE. The (S)-acids were produced enzymatically, whereas the (R)-acids were obtained via the chemical hydrolysis of the unreacted (R)-esters. The solvent and its water content had major effects on both reactivity and enantioselectivity. The methoxyethyl moiety of the ester had a key role concerning the reactivity of the substrates.

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(S)-1,2,3,4-Tetrahydroisoquinoline-1-acetic acidC11H13NO2Ee ⩾ 99%[α]D25=-46 (c 0.25, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (S)

Methyl (R)-1,2,3,4-tetrahydroisoquinoline-1-acetateC12H15NO2Ee ⩾ 99%[α]D25=+92 (c 1.0, CHCl3)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (R)

Ethyl (R)-1,2,3,4-tetrahydroisoquinoline-1-acetateC13H17NO2Ee = 96%[α]D25=+81 (c 0.2, CHCl3)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (R)

2-Methoxyethyl (R)-1,2,3,4-tetrahydroisoquinoline-1-acetateC14H19NO3Ee = 98%[α]D25=+64 (c 0.2, CHCl3)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (R)

(S)-6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-acetic acidC13H17NO4Ee ⩾ 99%[α]D25=-53.5 (c 0.25, H2O)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (S)

Ethyl (R)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-acetateC15H21NO4Ee = 98%[α]D25=+52 (c 1.0, CHCl3)[α]D25=+46.5 (c 1.22, EtOH)Source of chirality: lipase PS-catalyzed hydrolysisAbsolute configuration: (R)