Synthesis of new chiral keto alcohols by baker’s yeast

Fourteen chiral α- and β-keto alcohols 2a–2r were synthesized by the asymmetric reduction of their corresponding diketones 1a–1r via baker’s yeast. In addition, ten corresponding racemic α-keto alcohols were synthesized by the benzoin condensation of their corresponding aldehydes, which were used for the determination of the ee values through their chiral resolution on chiral HPLC. Amongst the 15 diketones, 1j and chiral α-keto alcohols 2i, 2j and chiral β-keto alcohol 2r are novel compounds. Six keto alcohols 2b, 2c, 2d, 2f, 2h and 2p were synthesized by baker’s yeast for the first time. There are some studies in the literature where baker’s yeast was applied to the diketones 1a, 1g, 1e, 1k and 1n under various conditions different to those reported herein. The yields and the ee values of these studies were not as high as ours. All of the keto alcohols synthesized were characterized by IR, NMR (1H and 13C), and MS. The relationship between the structure of the diketone and the yield, diastereoselectivity and enantiomeric excess is also discussed.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

2-Hydroxy-1,2-diphenyl ethanoneC14H12O2Ee 78%[α]D25=-81.5 (c 0.27, CH3COCH3)Source of chirality: BioreductionAbsolute configuration: (R)

2-Hydroxy-1,2-bis(2-methylphenyl)ethanoneC16H16O2Ee 98%[α]D25=-112 (c 0.08, CH3OH)Source of chirality: BioreductionAbsolute configuration: (R)

2-Hydroxy-1,2-bis(3-methylphenyl)ethanoneC16H16O2Ee 52%[α]D25=-51 (c 0.14, CH3OH)Source of chirality: BioreductionAbsolute configuration: (R)

2-Hydroxy-1,2-bis(2-methoxyphenyl)ethanoneC16H16O4Ee 53%[α]D25=-35.4 (c 0.1, CH3OH)Source of chirality: BioreductionAbsolute configuration: (R)

2-Hydroxy-1,2-bis(4-methoxyphenyl)ethanoneC16H16O4Ee 84%[α]D25=-75 (c 0.25, CH3OH)Source of chirality: BioreductionAbsolute configuration: (R)

2-Hydroxy-1-(2-methylphenyl)-2-phenyl-ethanoneC15H14O2Ee 78%[α]D25=-160 (c 0.25, CH3COCH3)Source of chirality: BioreductionAbsolute configuration: (R)

2-Hydroxy-1,2-bis(2-furanyl)-ethanoneC10H8O4Ee 62%[α]D25=-96.3 (c 0.08, CHCl3)Source of chirality: BioreductionAbsolute configuration: (R)

2-Hydroxy-1,2-bis(5-methyl-2-furanyl)-ethanoneC12H12O4Ee 72%[α]D25=-42.4 (c 0.66, CHCl3)Source of chirality: BioreductionAbsolute configuration: (R)

2-Hydroxy-1-(5-methyl-2-furanyl)-2-phenyl-ethanoneC13H12O3Ee 64%[α]D25=-66.6 (c 0.15, CHCl3)Source of chirality: BioreductionAbsolute configuration: (R)

1-(4-Methoxyphenyl)-2-hydroxy-1-tetradecaneoneC21H34O3Ee 50%[α]D25=-28.4 (c 0.12, CHCl3)Source of chirality: BioreductionAbsolute configuration: (R)

1-2-Dihydro-1-hydroxy-2-acenaphthyleneoneC12H8O2Ee 100%[α]D25=-73.2 (c 0.41, CHCl3)Source of chirality: BioreductionAbsolute configuration: (R)

1-Phenyl-3-hydroxy-1-butanoneC10H12O2Ee 100%[α]D25=-68.1 (c 0.11, CHCl3)Source of chirality: BioreductionAbsolute configuration: (R)

(1S,2R)-2-Hydroxycyclohexyl-phenylmethanoneC13H16O2Ee 100%[α]D25=+40 (c 0.1, CHCl3)Source of chirality: BioreductionAbsolute configuration: (1S,2R)