Asymmetric synthesis of palitantin by an enzymatic and organocatalytic approach

The natural enantiomer of the fungal metabolite (+)-palitantin has been synthesized by adopting a chemoenzymatic and organocatalytic approach. Lipase catalyzed kinetic resolution, Sharpless asymmetric dihydroxylation and organocatalytic asymmetric hydroxymethylation are the key steps involved in the total synthesis of the target molecule.

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Acetic acid (S)-5-oxo-cyclohex-3-enylmethyl esterC9H12O3Ee = 98%[α]D29=+25.7 (c 1.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (5S)

(R)-5-Hydroxymethyl-cyclohex-2-enoneC7H10O2Ee = 99%[α]D29=-32.85 (c 1.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (5R)

(2R,3R,5R)-5-(tert-Butyl-diphenyl-silanyloxymethyl)-2,3-dihydroxy-cyclohexanoneC23H30O4Si[α]D29=-18.5 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,5R)

(3R,6R,7R)-6-(tert-Butyl-diphenyl-silyloxymethyl)-2,2-dimethyl-tetrahydro-benzo[1,3]dioxol-4-oneC26H34O4Si[α]D29=-5.5 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,6R,7R)

(3R,6R,7R)-6-((1E,3E)-Hepta-1,3-dienyl)-2,2-dimethyl-tetrahydro-benzo[1,3]dioxol-4-oneC16H24O3[α]D29=-7.9 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,6R,7R)

(2R,3R,5R)-5-((1E,3E)-Hepta-1,3-dienyl)-2,3-dihydroxy-cyclohexanoneC13H20O3[α]D29=-6.7 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,5R)

(2R,3S,5R,6R)-3-((1E,3E)-Hepta-1,3-dienyl)-5,6-dihydroxy-2-hydroxymethyl-cyclohexanoneC14H22O4[α]D29=+4.4 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S,5R,6R)