Synthesis of new (R)-secondary carbinols with different structures via enzymatic resolution

The present study deals with the biocatalytic enantioselective synthesis of 19 new chiral alcohols with alkyl (C11–C19) and phenyl, substituted phenyl, heteroaromatic, and naphthyl groups 4a–4z with an (R)-configuration and high enantiomeric excess (∼100%). The corresponding ketones 1a–1z were synthesized and then reduced with NaBH4 to their racemic alcohols 2a–2z, which were converted into their racemic acetyl derivatives 3a–3z. Enzymes of four different types were used for the enantioselective hydrolysis of these acetyl compounds 3a–3z. The optimal reaction conditions for these four enzymes were established by investigating the enantiomeric excesses by chiral HPLC. AmanolipasefromBurkholdericacepacia (Pseudomonascepacia) AL-PS was determined as the best enzyme in this work. This study presents an environmentally friendly and green chemistry method for the synthesis of these new (R)-chiral carbinols 4a–4z.

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1-Phenyl-1-tridecanolC19H32OEe 99%[α]D25=+36.6 (c 1.1, hexane)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-Phenyl-1-tetradecanolC20H34OEe 99%[α]D25=+42.6 (c 1.1, hexane)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-Phenyl-1-pentadecanolC21H36OEe 92%[α]D25=+18.9 (c 1.1, hexane)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-Phenyl-1-hexadecanolC22H38OEe 99%[α]D25=+21.3 (c 1.1, hexane)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-Phenyl-1-nonadecanolC25H44OEe 86%[α]D25=+22 (c 1.1, hexane)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-Phenyl-1-eicosanolC26H46OEe 92%[α]D25=+17.4 (c 1.1, hexane)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-(p-Methylphenyl)-1-tridecanolC20H34OEe 100%[α]D25=+28.4 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-(p-Methoxyphenyl)-1-tetradecanolC21H36O2Ee 100%[α]D25=+17.9 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-(p-Bromophenyl)-1-tetradecanolC20H33BrOEe 92%[α]D25=+13.9 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-(p-Hydroxyphenyl)-1-tetradecanolC20H34O2Ee 22%[α]D25=+4.6 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-(2-Furyl)-1-hexadecanolC20H36O2Ee 72%[α]D25=+8.3 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-(2-Thenyl)-1-hexadecanolC20H36OSEe 70%[α]D25=+11.7 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

1-(Naphthlalen-2-yl)-1-tridecanolC23H34OEe 100%[α]D25=+52.1 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

(4-t-Butylphenyl)(phenyl)methanolC17H20OEe 90%[α]D25=+52.9 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

2-NonadecanolC19H40OEe 80%[α]D25=-10 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

3-OctadecanolC18H38OEe 91%[α]D25=-18 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

4-HeptadecanolC17H34OEe 57%[α]D25=-8 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)

4-HenicosanolC21H44OEe 60%[α]D25=-15 (c 1.1, chloroform)Source of chirality: enzymatic enantioselective hydrolysisAbsolute configuration: (R)