Lipase mediated sequential resolution of aromatic β-hydroxy esters using fatty acid derivatives

The lipase-catalyzed kinetic resolution of a series of aromatic β-hydroxy esters in organic media has been investigated. Decanoic acid and its esters were successfully used as acyl donors for selective O-acylation. The regio- and enantioselective enzymatic hydrolysis of the decanoate moiety of the diesters was also investigated. The effects of water, reaction temperature, and solvent type, and also the influence of substrates structure on the catalytic behavior of potential commercially available lipases were studied. A novel procedure was developed for the efficient and highly stereoselective synthesis of both enantiomers of both novel and known target compounds.

Figure optionsDownload as PowerPoint slide

(S)-Ethyl 3-hydroxy-3-(5-phenylfuran-2-yl)propanoateC15H16O4[α]D20=-40.7 (c 1.0, CHCl3)Ee >99% on Chiralpak IA HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (S)

(S)-Ethyl 3-(5-(4-chlorophenyl)furan-2-yl)-3-hydroxypropanoateC15H15ClO4[α]D25=-35.2 (c 1.0, CHCl3)Ee >99% on Chiralpak IC HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (S)

(R)-3-Ethoxy-3-oxo-1-phenylpropyl decanoateC21H32O4[α]D25=+22.1 (c 1.0, CHCl3)Ee = 90% on tandem Chiralpak IA-AS-H HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-3-Ethoxy-1-(4-methoxyphenyl)-3-oxopropyl decanoateC22H34O5[α]D25=+36.9 (c 1.0, CHCl3)Ee = 98.1% on tandem Chiralpak IA-AS-H HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-1-(4-Chlorophenyl)-3-ethoxy-3-oxopropyl decanoateC21H31ClO4[α]D25=+30.4 (c 1.0, CHCl3)Ee = 90.6% on Chiralpak IA HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-3-Ethoxy-3-oxo-1-(thiophen-2-yl)propyl decanoateC19H30O4S[α]D25=+45.8 (c 1.0, CHCl3)Ee = 90.3% on Chiralpak IB HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-3-Ethoxy-1-(furan-2-yl)-3-oxopropyl decanoateC19H30O5[α]D25=+53.6 (c 1.0, CHCl3)Ee = 71.9% on Chirapak IA HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-3-Ethoxy-3-oxo-1-(thiophen-3-yl)propyl decanoateC19H30O4S[α]D25=+38.9 (c 1.0, CHCl3)Ee = 83.2% on Chiralpak IB HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-3-Ethoxy-1-(furan-3-yl)-3-oxopropyl decanoateC19H30O5[α]D25=+31.1 (c 1.0, CHCl3)Ee = 77.5% on Chiralpak IB HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-1-(Benzo[b]thiophen-2-yl)-3-ethoxy-3-oxopropyl decanoateC23H32O4S[α]D25=+50.2 (c 1.0, CHCl3)Ee = 89.5% on Chiralpak IA HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-1-(Benzofuran-2-yl)-3-ethoxy-3-oxopropyl decanoateC23H32O5[α]D25=+37.6 (c 1.0, CHCl3)Ee = >99% on Chiralpak IC HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-1-(Benzo[b]thiophen-3-yl)-3-ethoxy-3-oxopropyl decanoateC23H32O4S[α]D25=+22.1 (c 1.0, CHCl3)Ee = 76.6% on Chiralpak IA HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-1-(Benzofuran-3-yl)-3-ethoxy-3-oxopropyl decanoateC23H32O5[α]D25=+22.9 (c 1.0, CHCl3)Ee = 85.4% on Chiralpak IC HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-3-Ethoxy-3-oxo-1-(5-phenylfuran-2-yl)propyl decanoateC25H34O5[α]D25=+21.1 (c 1.0, CHCl3)Ee = 81.7% on Chiralpak IA HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)

(R)-1-(5-(4-Chlorophenyl)furan-2-yl)-3-ethoxy-3-oxopropyl decanoateC25H33ClO5[α]D25=+12 (c 1.0, CHCl3)Ee >99% on Chiralpak IC HPLC columnSource of chirality: Enzymatic resolution by lipase from Candida rugosaAbsolute configuration: (R)