Total synthesis of 8-methoxygoniodiol related compounds via chiron approach

The stereoselective synthesis of 8-methoxygoniodiol related compounds was accomplished by using readily available δ-gluconolactone as a chiral source. The stereoselective addition of an aryl Grignard reagent on an aldehyde, stereoselective reduction of a keto group and regioselective opening of a chiral epoxide by ethyl propiolate are the key steps involved in this synthesis.

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(R)-Methyl 2-hydroxy-2-((4R,4′R,5R)-2,2,2′,2′-tetramethyl-4,4′-bi(1,3-dioxolan)-5-yl)acetateC13H22O7[α]D25=+10.2 (c 1.0, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (2R,4R,4′R,5R)

(S)-1-((4R,4′R,5R)-2,2,2′,2′-Tetramethyl-4,4′-bi(1,3-dioxolan)-5-yl)ethane-1,2-diolC12H22O6[α]D25=+7.2 (c 1.75, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (2R,4R,4′R,5R)

(R)-Phenyl((4R,4′R,5R)-2,2,2′,2′-tetramethyl-4,4′-bi(1,3-dioxolan)-5-yl)methanolC17H24O5[α]D25=+15.8 (c 1.0, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (2R,4R,4′R,5R)

(4R,4′R,5R)-5-((R)-Hexyloxy(phenyl)methyl)-2,2,2′,2′-tetramethyl-4,4′-bi(1,3-dioxolane)C23H36O5[α]D25=+29.3 (c 7.85, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (2R,4R,4′R,5R)

(4R,4′R,5R)-5-((R)-Dodecyloxy(phenyl)methyl)-2,2,2′,2′-tetramethyl-4,4′-bi(1,3-dioxolane)C29H48O5[α]D25=+26.5 (c 4.1, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (2R,4R,4′R,5R)

((4R,5R)-5-((R)-Hexyloxy(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methanolC19H30O4[α]D25=+43.9 (c 1.65. CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

((4R,5R)-5-((R)-Dodecyloxy(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methanolC25H42O4[α]D25=+31.5 (c 1.40, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

(4R,5S)-4-((R)-Hexyloxy(phenyl)methyl)-5-(iodomethyl)-2,2-dimethyl-1,3-dioxolaneC19H29IO3[α]D25=+53.2 (c 1.75, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

(4R,5S)-4-((R)-Dodecyloxy(phenyl)methyl)-5-(iodomethyl)-2,2-dimethyl-1,3-dioxolaneC25H41IO3[α]D25=+33.3 (c 0.90, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

(1R,2R)-2-(Hexyloxy)-1-((R)-oxiran-2-yl)-2-phenylethanolC16H24O3[α]D25=+28.0 (c 0.25, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

(1R,2R)-2-(Dodecyloxy)-1-((R)-oxiran-2-yl)-2-phenylethanolC22H36O3[α]D25=-34 (c 1.0, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

(5R,6S,7R)-Ethyl 6-(tert-butyldimethylsilyloxy)-7-(hexyloxy)-5-hydroxy-7-phenylhept-2-ynoateC27H44O5Si[α]D25=+71.0 (c 1.0, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (5R,6S,7R)

(5R,6S,7R)-Ethyl 6-(tert-butyldimethylsilyloxy)-7-(dodecyloxy)-5-hydroxy-7-phenylhept-2-ynoateC33H56O5Si[α]D25=+54.10 (c 1.0, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (5R,6S,7R)

(R)-6-((1S,2S)-1-Hydroxy-2-methoxy-2-phenylethyl)-5,6-dihydropyran-2-oneC14H16O4[α]D25=-0.8 (c 0.50, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (5R,6S,7R)

(R)-6-((1S,2R)-2-(Hexyloxy)-1-hydroxy-2-phenylethyl)-5,6-dihydropyran-2-oneC19H26O4[α]D25=-3.5 (c 1.0, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (5R,6S,7R)

Phenyl((4R,4′R,5S)-2,2,2′,2′-tetramethyl-4,4′-bi(1,3-dioxolan)-5-yl)methanoneC17H22O5[α]D25=+11.6 (c 0.8, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

(S)-Phenyl((4R,4′R,5R)-2,2,2′,2′-tetramethyl-4,4′-bi(1,3-dioxolan)-5-yl)methanolC17H24O5[α]D25=+15.7 (c 1.0, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

(4R,4′R,5R)-5-((S)-Methoxy(phenyl)methyl)-2,2,2′,2′-tetramethyl-4,4′-bi(1,3-dioxolane)C18H26O5[α]D25=+59.6 (c 0.5, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5R)

((4R,5R)-5-((S)-Methoxy(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methanolC14H20O4[α]D25=+55.9 (c 2.1, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5S)

(4S,5R)-4-(Iodomethyl)-5-((S)-methoxy(phenyl)methyl)-2,2-dimethyl-1,3-dioxolaneC14H19IO3[α]D25=+63.1 (c 1.0, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5S)

(1R,2S)-2-Methoxy-1-((R)-oxiran-2-yl)-2-phenylethanolC11H14O3[α]D25=+36.9 (c 2.9, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (4R,4′R,5S)

(5R,6S,7S)-Ethyl 6-(tert-butyldimethylsilyloxy)-5-hydroxy-7-methoxy-7-phenylhept-2-ynoateC22H34O5Si[α]D25=+60.5 (c 1.4, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (5R,6S,7S)

(R)-6-((1S,2R)-2-(Dodecyloxy)-1-hydroxy-2-phenylethyl)-5,6-dihydropyran-2-oneC25H38O4[α]D25=+23.4 (c 0.35, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (5R,6S,7R)