New chiral building blocks from acetovanillone using lipase A and B from Candida antarctica

Acetovanillone has been used as the starting material for the synthesis of a series of secondary alcohols, which were resolved by lipase catalyzed esterification. 1-(4-Benzyloxy-3-methoxyphenyl)ethanol was efficiently resolved using immobilized lipase B from Candida antarctica (Novozym 435, CAL-B), whereas immobilized lipase A from C. antarctica (Novozym 735, CAL-A) was the lipase of choice for the resolution of the corresponding 2-bromo- and 2-chloro-derivatives. The enantioenriched alcohols are new building blocks for potential use in the synthesis of bioactive compounds.

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(S)-1-(4-(Benzyloxy)-3-methoxyphenyl)ethanolC16H18O3Ee = 99%[α]D20=-27.9 (c 1.00 CHCl3)Source of chirality: resolution by lipaseAbsolute configuration: S

(R)-1-Acetoxy-1-(4-(benzyloxy)-3-methoxyphenyl)ethaneC18H20O4Ee = 92%[α]D20=+78.6 (c 1.00 CHCl3)Source of chirality: resolution by lipaseAbsolute configuration: R

(R)-2-Bromo-1-(4-(benzyloxy)-3-methoxyphenyl)ethanolC16H17BrO3Ee = 94%[α]D20=+5.8 (c 1.00 CHCl3)Source of chirality: resolution by lipaseAbsolute configuration: R

(S)-1-Acetoxy-2-bromo-1-(4-(benzyloxy)-3-methoxyphenyl)ethaneC18H19BrO4Ee = 98%[α]D20=+43.1 (c 1.00 CHCl3)Source of chirality: resolution by lipaseAbsolute configuration: S

(R)-2-Chloro-1-(4-(benzyloxy)-3-methoxyphenyl)ethanolC16H17ClO3Ee = 97%[α]D20=-12.1 (c 1.00 MeOH)Source of chirality: resolution by lipaseAbsolute configuration: R

(S)-1-Acetoxy-2-chloro-1-(4-(benzyloxy)-3-methoxyphenyl)ethaneC18H19ClO4Ee = 95%[α]D20=+39.4 (c 1.00 CHCl3)Source of chirality: resolution by lipaseAbsolute configuration: S