Highly stereoselective synthesis of antitumor agents: both enantiomers of goniothales diol, altholactone, and isoaltholactone

A flexible stereoselective route to synthesize both enantiomers of the highly functionalized substituted tetrahydrofurans and α,β-unsaturated-δ-lactones, goniothales diol, altholactone, and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulfonic acid.

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Ethyl 3-[3-phenyl-(2S,3S)-oxiran-2-yl]-(E)-2-propenoateC13H14O3[α]D20=-136.5 (c 1.6, CHCl3)Source of chirality: Sharpless asymmetric epoxidationAbsolute configuration: (2S,3S)

Ethyl (2R,3S)-dihydroxy-3-[3-phenyl-(2S,3S)-oxiran-2-yl]-(2R)-propanoateC13H16O5[α]D20=-45.7 (c 1, CHCl3)Source of chirality: Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylationAbsolute configuration: [2R,3S(2′S,3′S)]

Ethyl (2S,3R)-dihydroxy-3-[3-phenyl-(2S,3S)-oxiran-2-yl]-(2S)-propanoateC13H16O5[α]D20=-55.3 (c 1, CHCl3)Source of chirality: Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylationAbsolute configuration: [2S,3R(2′S,3′S)]

Ethyl 3,4-dihydroxy-5-phenyl-(2R,3S,4R,5R)-tetrahydro-2-furancarboxylateC13H16O5[α]D20=+24.5 (c 1, CHCl3)Absolute configuration: (2R,3S,4R,5R)

Ethyl 3,4-dihydroxy-5-phenyl-(2S,3R,4R,5R)-tetrahydro-2-furancarboxylateC13H16O5[α]D20=+15.5 (c 1.4, CHCl3)Absolute configuration: (2S,3R,4R,5R)

Ethyl 2,2-dimethyl-6-phenyl-(3aR,4S,6R,6aR)-perhydrofuro[3,4-d][1,3]dioxole-4-carboxylateC16H20O5[α]D20=-19.5 (c 1.1, CHCl3)Absolute configuration: (3aR,4S,6R,6aR)

Ethyl-3-[2,2-dimethyl-6-phenyl-(3aR,4S,6S,6aS)-perhydrofuro[3,4-d][1,3]dioxol-4-yl]-(Z)-2- propenoateC18H22O5[α]D20=+97.3 (c 1.5, CHCl3)Absolute configuration: (3aR,4S,6S,6aS)

Methyl 3,4-di-tert-butyldimethylsilanyloxy-5-phenyl-(2S,3R,4S,5S)-tetrahydro-2-furancarboxylateC25H44O5Si2[α]D20=+19.2 (c 1.8, CHCl3)Absolute configuration: (2S,3R,4S,5S)

Methyl 3-[3,4-di-tert-butyldimethylsilanyloxy-5-phenyl-(2S,3R,4R,5R)-tetra-hydro-2-furanyl]-(Z)-2-propenoateC26H44O5Si2[α]D20=+103.1 (c 1, CHCl3)Absolute configuration: (2S,3R,4R,5R)

Methyl 3-[3,4-di-tert-butyldimethylsilanyloxy-5-phenyl-(2R,3S,4S,5S)-tetrahydro-2-furanyl]propanoateC26H46O5Si2[α]D20=-18.9 (c 1, CHCl3)Absolute configuration: (2R,3S,4S,5S)