Synthesis of gingerol and diarylheptanoids

The synthesis of gingerol 1 and related compounds 2–5 along with diarylheptanoids 6–8 has been accomplished using a Keck allylation, Crimmins’ aldol reaction, aldehyde coupling with acetylene, and chelation controlled reductions as the key reactions. The absolute configuration of these molecules was confirmed by preparing their acetonide derivatives and by comparison of the NMR data with natural compounds.

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(S)-Non-1-en-4-olC9H18O[α]D25=-10.7 (c 2.0, CHCl3)Absolute configuration: (4S)Source of chirality: asymmetric synthesis

(S)-tert-Butyldimethyl(non-1-en-4-yloxy)silaneC19H30O4[α]D25=-15.7 (c 2.0, CHCl3)Absolute configuration: (4S)Source of chirality: asymmetric synthesis

(S)-1-(4-(Benzyloxy)-3-methoxyphenyl)-5-(tert-butyldimethylsilyloxy)dec-1-yn-3-oneC30H42O4Si[α]D25=-12.7 (c 1.0, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(S)-5-(tert-Butyldimethylsilyoxy)-1-(4-hydroxy-3-methoxyphenyl)decan-3-oneC23H40O4Si[α]D25=+13.5 (c 2.0, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(S)-5-Hydroxy-1-(4-hydroxy-3-methoyphenyl)decane-3-oneC17H26O4[α]D25=+22.7 (c 2.0, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(3R,5S)-1-(4-Hydroxy-3-methoxyphenyl)decane-3,5-diolC17H28O4[α]D25=+5.5 (c 1.0, CHCl3)Absolute configuration: (3R,5S)Source of chirality: asymmetric synthesis

(3S,5S)-1-(4-Hydroxy-3-methoxyphenyl)decane-3,5-diolC17H28O4[α]D25=-1.0 (c 3.0, CHCl3)Absolute configuration: (3S,5S)Source of chirality: asymmetric synthesis

4-(2-((4R,6S)-2,2-Dimethyl-6-pentyl-1,3-dioxan-4-yl)ethyl)-2-methoxyphenolC20H32O4[α]D25=+17.9 (c 1.0, CHCl3)Absolute configuration: (4R,6S)Source of chirality: asymmetric synthesis

4-(2-((4S,6S)-2,2-Dimethyl-6-pentyl-1,3-dioxan-4-yl)ethyl)-2-methoxyphenolC20H32O4[α]D25=+19.0 (c 1.0, CHCl3)Absolute configuration: (4S,6S)Source of chirality: asymmetric synthesis

(4R,6S)-4-(4-(Benzyloxy)-3-methoxyphenethyl)-2,2-dimethyl-6-pentyl-1,3-dioxaneC27H38O4[α]D25=+8.6 (c 1.0, CHCl3)Absolute configuration: (4R,6S)Source of chirality: asymmetric synthesis

(3R,5S)-1-(4-(Benzyloxy-3-methoxyphenyl)decane-3,5-diolC24H34O4[α]D25=+5.3 (c 1.0, CHCl3)Absolute configuration: (3R,5S)Source of chirality: asymmetric synthesis

(3R,5S)-1-(4-(Benzyloxy)-3-methoxyphenyl)decane-3,5-diyl diacetateC28H38O6[α]D25=-3.2 (c 2.0, CHCl3)Absolute configuration: (3R,5S)Source of chirality: asymmetric synthesis

(3R,5S)-1-(4-Hydroxy-3-methoxyphenyl)decane-3,5-diyl diacetateC21H32O6[α]D25=-3.6 (c 1.0, CHCl3)Absolute configuration: (3R,5S)Source of chirality: asymmetric synthesis

(4R,6S)-4-(3,4-DimethoxylphenetHyl)-2,2-dimethyl-6-pentyl-1,3-dioxanC21H34O4[α]D25=+8.9 (c 1.5, CHCl3)Absolute configuration: (4R,6S)Source of chirality: asymmetric synthesis

(3R,5S)-1-(3,4-Dimethoxyphenyl)decane-3,5-diolC18H30O4[α]D25=+9.8 (c 3.0, CHCl3)Absolute configuration: (3R,5S)Source of chirality: asymmetric synthesis

(3R,5S)-1-(3,4-Dimethoxyphenyl)decane-3,5-diyl diacetateC22H34O6[α]D25=-1.2 (c 3.0, CHCl3)Absolute configuration: (3R,5S)Source of chirality: asymmetric synthesis

(S)-1-((S)-4-Benzyl-2-thioxothiazolidin-3-yl)-3-hydroxy-5-(3,4,5-trimethoxyphenyl)pentan-1-oneC24H29NO5S2[α]D25=+16.6 (c 0.9, CHCl3)Absolute configuration: (3S,4S)Source of chirality: asymmetric synthesis

(S)-1-((S)-4-Benzyl-2-thioxothiazolidin-3-yl)-3-(tert-butyldimethylsilyloxy)-5-(3,4,5 trimethoxyphenyl)pentan-1-oneC30H43NO5S2Si[α]D25=+132.2 (c 0.8, CHCl3)Absolute configuration: (3S,4S)Source of chirality: asymmetric synthesis

(S)-5-(tert-Butyldimethylsilyloxy)-1,7-bis(3,4,5-trimethoxyphenyl)hept-1-yn-3-oneC31H44O8Si[α]D25=-3.3 (c 0.6, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(S)-5-(tert-Butyldimethylsilyloxy)-1,7-bis(3,4,5-trimethoxyphenyl)heptan-3-oneC31H48O8Si[α]D25=-12.8 (c 0.7, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(S)-5-Hydroxy-1,7-bis(3,4,5-trimethoxyphenyl)heptan-3-oneC25H34O8[α]D25=-2.4 (c 1.2, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(3S,5S)-1,7-Bis(3,4,5-trimethoxyphenyl)heptane-3,5-diolC25H36O8[α]D25=+3.1 (c 0.5, CHCl3)Absolute configuration: (3S,5S)Source of chirality: asymmetric synthesis

(3S,5S)-1,7-Bis(3,4,5-trimethoxyphenyl)heptane-3,5-diyl diacetateC29H40O10[α]D25=+4.7 (c 0.5, CHCl3)Absolute configuration: (3S,5S)Source of chirality: asymmetric synthesis

(S)-1-((S)-4-Benzyl-2-thioxothiazolidin-3-yl)-5-(4-(benzyloxy)-3-methoxyphenyl)-3-hydroxypentan-1-oneC29H31NO4S2[α]D25=+131.8 (c 1.1, CHCl3)Absolute configuration: (3S,4S)Source of chirality: asymmetric synthesis

(S)-1-((S)-4-Benzyl-2-thioxothiazolidin-3-yl)-5-(4-(benzyloxy)-3-methoxyphenyl)-3-(methoxymethoxy)pentan-1-oneC31H35NO5S2[α]D25=+97.9 (c 2.9, CHCl3)Absolute configuration: (3S,4S)Source of chirality: asymmetric synthesis

(S)-1,7-Bis(4-(benzyloxy)-3-methoxyphenyl)-5-(methoxymethoxy)hept-1-yn-3-oneC37H38O7[α]D25=-6.2 (c 0.8, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(S)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-5-(methoxymethoxy)heptan-3-oneC23H30O7[α]D25=+5.7 (c 1.4, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(S)-5-Hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-oneC21H26O6[α]D25=+4.0 (c 1.0, CHCl3)Absolute configuration: (5S)Source of chirality: asymmetric synthesis

(3S,5S)-1,7-Bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-diolC21H28O6[α]D25=-13.5 (c 1.0, EtOH)Absolute configuration: (3S,4S)Source of chirality: asymmetric synthesis