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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

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)