Stereoselective and facile total synthesis of (+)-goniodiol, a styryllactone from carbohydrates

The stereoselective synthesis of (+)-goniodiol, a cytotoxic styryllactone, has been accomplished in 10 steps starting from inexpensive and readily available d-manitol and δ-gluconolactone involving the direct and straightforward reaction conditions of Grignard addition, chain elongation, and hydroboration, thus making the synthesis simple and convenient.

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(R)-1-((4R,4′R,5R)-2,2,2′,2′-Tetramethyl-4,4′-bi(1,3-dioxolan)-5-yl)ethane-1,2-diolC12H22O6[α]D28=+12.8 (c 1, CH2Cl2)Source of chirality: from starting material, d-mannitolAbsolute configuration: (1R,4R,4′R,5R)

(4S,4′R,5R)-2,2,2′,2′-Tetramethyl-5-vinyl-4,4′-bi(1,3-dioxolane)C12H20O4[α]D28=-6.0 (c 2.98, CHCl3)Source of chirality: from starting material, d-mannitolAbsolute configuration: (4S,4′R,5R)

(R)-1-((4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)ethane-1,2-diolC9H16O4[α]D28=+6.9 (c 0.58, CH2Cl2).Source of chirality: from starting material, d-mannitolAbsolute configuration: (1R,4R,5R)

(S)-((4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)(phenyl)methanolC14H18O3[α]D28=+4.8 (c 0.21, CH2Cl2)Source of chirality: from starting material, d-mannitolAbsolute configuration: (1R,4R,5R)

(R)-((4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)(phenyl)methanolC14H18O3[α]D28=+15.1 (c 0.2, CH2Cl2)Source of chirality: from starting material, d-mannitolAbsolute configuration: (1S,4R,5R)

tert-Butyl((S)-((4S,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4 yl)(phenyl)methoxy)diphenylsilaneC30H36O3Si[α]D28=+47.0 (c 1, CH3OH)Source of chirality: from starting material, d-mannitolAbsolute configuration: (1S,4S,5R)

tert-Butyldiphenyl((R)-phenyl((4R,4′R,5S)-2,2,2′,2′-tetramethyl-4,4′-bi(1,3-dioxolan)-5-yl)methoxy)silaneC33H42O5Si[α]D25=+18.4 (c 1, CHCl3)Source of chirality: from starting material, d-glucono-δ-lactoneAbsolute configuration: (1R,4R,4′R,5S)

(R)-1-((4R,5S)-5-((S)-(tert-Butyldiphenylsilyloxy)(phenyl)methyl)-2,2 dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diolC30H38O5Si[α]D28=+39.0 (c 1, CHCl3)Source of chirality: from starting material, d-glucono-δ-lactoneAbsolute configuration: (1R,4R,5S,5S)

2-((4R,5S)-5-((S)-(tert-Butyldiphenylsilyloxy)(phenyl)methyl)-2,2-dimethyl-1,3 dioxolan-4-yl)ethanolC30H38O4Si[α]D28=+45.3 (c 1, CH3OH)Source of chirality: from starting material, d-mannitolAbsolute configuration: (4R,5S,5S)

(Z)-Methyl4-((4R,5S)-5-((S)-(tert-butyldiphenylsilyloxy)(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enoateC33H40O5Si[α]D28=+50.9 (c 1, CH3OH)Source of chirality: from starting material, d-mannitolAbsolute configuration: (4R,5S,5S)

(R)-6-((1S,2R)-2-(tert-Butyldiphenylsilyloxy)-1-hydroxy-2-phenylethyl)-5,6-dihydropyran-2-oneC29H32O4Si[α]D28=+20.5 (c 0.75, CH3OH)Source of chirality: from starting material, d-mannitolAbsolute configuration: (6R,1S,2R)

(R)-6-((1R,2R)-1,2-Dihydroxy-2-phenylethyl)-5,6-dihydropyran-2-oneC13H14O4[α]D28=+72.2 (c 0.68, CHCl3)Source of chirality: from starting material, d-mannitolAbsolute configuration: (6R,1R,2R)