Chemoenzymatic asymmetric synthesis of harzia lactone A stereomers

A facile chemoenzymatic synthesis of the harzia lactone A enantiomers was developed. A lipase-catalyzed acylation and an enantio-controlled substrate and reagent-controlled Sharpless’ asymmetric dihydroxylation are the key features of the synthesis.

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(S)-1-Phenylpent-4-ene-2-olC11H14O[α]D22=+12.2 (c 1.84, CHCl3)Source of chirality = lipase catalyzed resolutionAbsolute configuration: (S)

(R)-2-Acetoxy-1-phenylpent-4-eneC13H16O2[α]D22=-17.5 (c 1.16, CHCl3)Source of chirality = lipase catalyzed resolutionAbsolute configuration: (R)

(2R,4R)-1-tert-Butyldiphenylsiloxy 5-phenylpentane-2,4-diolC37H34O3Si[α]D22=-4.0 (c 1.26, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4R)

(2S,4R)-1-tert-Butyldiphenylsiloxy5-phenylpentane-2,4-diolC37H34O3Si[α]D22=+16.0 (c 1.52, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4R)

(2R,4R)-1-tert-Butyldiphenylsiloxy 2,4-isopropanedioxypentaneC40H38O3Si[α]D22=-5.0 (c 1.28, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4R)

(2R,4R)-2,4-Isopropanedioxypentan-1-olC14H20O3[α]D22=-9.8 (c 4.86, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4R)

(2R,4R)-2,4-IsopropanedioxypentanalC14H18O3[α]D22=-6.8 (c 1.26, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4R)

(3R,5R)-3-Hydroxy-5-phenylmethyl dihydrofuran-2-oneC11H12O3[α]D22=+38.6 (c 0.702, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (3R,5R)

(2R,4S)-4-Acetoxy-5-phenylpentane-1,2-diolC13H18O4[α]D22=+14.8 (c 0.88, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4R)

(2R,4S)-1-tert-Butyldimethylsiloxy 2-hydroxy-4-acetoxy-5-phenylpentaneC19H32O4Si[α]D22=+10.4 (c 1.18, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4S)

(2R,4S)-1-tert-Butyldimethylsiloxy-2,4-isopropanedioxy-5-phenylpentaneC20H34O3Si[α]D22=+7.5 (c 0.860, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4S)

(2R,4S)-2,4-Isopropanedioxy-5-phenylpentan-1-olC14H20O3[α]D22=+5.2 (c 0.882, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4S)

(2R,4S)-2,4-Isopropanedioxy-5-phenylpentanalC14H18O3[α]D22=+5.9 (c 1.04, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (2R,4S)

(3R,5S)-3-Hydroxy-5-phenylmethyl dihydrofuran-2-oneC11H12O3[α]D22=+8.9 (c 0.648, CHCl3)Source of chirality = lipase catalyzed resolution and asymmetric dihydroxylationAbsolute configuration: (3R,5S)