Stereoselective total synthesis of styryl-lactones: (+)-crassalactones B and C, (+)-howiionol A, (+)-tricinnamate, (+)-goniofufurone and (+)-dicinnamoyl goniofufurone

The total synthesis of (+)-crassalactone B, (+)-crassalactone C, (+)-howiionol A, (+)-tricinnamate, (+)-goniofufurone, and (+)-dicinnamoyl goniofufurone is achieved by a ‘chiron approach’ starting from diacetone d-glucose (DAG). Mitsunobu inversion, Wittig olefination and ring closing metatheses were used as key steps for (+)-howiionol A and (+)-tricinnamate. Meldrum’s acid was used for the synthesis of (+)-crassalactone C, (+)-goniofufurone, and (+)-dicinnamoyl goniofufurone. Yamaguchi esterification was used for (+)-crassalactone B, while a Grignard reaction followed by concomitant deallylation was first reported in the synthesis of (+)-dicinnamoyl goniofufurone.

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(+)-Crassalactone BC22H20O6[α]D = +31.6 (c 1.0, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (4R,5S,6R,7R,8R)

(+)-Crassalactone CC22H20O6[α]D = =+108.0 (c 0.37, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (4R,5S,6R,7R,8R)

(+)-Dicinnamoyl goniofufuroneC31H26O7[α]D = =−102.7 (c 0.24, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (4R,5S,6R,7R,8R)

(+)-GoniofufuroneC13H14O5[α]D = =+20.0 (c 0.5, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (4R,5S,6R,7R,8R)

(+)-Howiionol AC22H20O6[α]D = =+101.4 (c 0.22, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (4R,5S,6R,7R,8R)

(+)-TricinnamateC40H32O8[α]D = =+180.0 (c 0.1, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (5S,6R,7R,8R)

(3aR,5S,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-tetrahydro furo [2,3-d][1,3]dioxol-6-olC15H24O6[α]D = −58.3 (c 0.51, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (3aR,5S,6S,6aR),5R

(R)-1-((3aR,5R,6S,6aR)-6-(Allyloxy)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3] dioxol-5-yl)ethane-1,2-diolC12H20O6[α]D = −106.0 (c 0.5, CHCl3)Source of chirality: d-glucoseAbsolute configuration: R, 1(3aR,5R,6S,6aR)

(S)-((3aR,5R,6S,6aR)-6-(Allyloxy)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(phenyl)methanolC17H22O5[α]D = −10.7 (c 1.2, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: S, (3aR,5R,6S,6aR)

(R)-((3aR,5R,6S,6aR)-6-(Allyloxy)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(phenyl)methyl cinnamateC26H28O6[α]D = +79.0 (c 0.75, CHCl3)Source of chirality: d-glucose and asymmetricAbsolute configuration: R, (3aR,5R,6S,6aR)

(R)-((3aR,5R,6S,6aR)-6-(Allyloxy)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(phenyl)methanolC17H22O5[α]D = −48.7 (c 0.37, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: R, (3aR,5R,6S,6aR)

(3aR,5R,6S,6aR)-6-(Allyloxy)-5-((R)-benzyloxy(phenyl)methyl)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxoleC24H28O5[α]D = −36.2 (c 2.0, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (3aR,5R,6S,6aR),5R

(3R,4R,5R)-4-(Allyloxy)-5-((R)-benzyloxy(phenyl)methyl)-tetrahydrofuran-2,3-diolC21H24O5[α]D = -41.2 (c 1.4, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (3R,4R,5R),5R

(3aR,5R,6S,6aS)-6-(Allyloxy)-5-((R)-benzyloxy(phenyl)methyl)-tetrahydro furo[3,2-b]furan-2(5H)-oneC23H24O5[α]D = −0.9 (c 0.44, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (3aR,5R,6S,6aS),5R

(3aR,5S,6S,6aR)-5-((R)-Benzyloxy(phenyl)methyl)-6-hydroxy-tetrahydrofuro[3,2-b]furan-2(5H)-oneC20H20O5[α]D = −57.7 (c 0.44, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (3aR,5S,6S,6aR),5R

(2R,3S,3aS,6aR)-2-((R)-Benzyloxy(phenyl)methyl)-5-oxo-hexahydrofuro[3,2-b]furan-3-yl cinnamateC29H26O6[α]D = −41.3 (c 1.0, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (2R,3S,3aS,6aR),2R

(3R,4R,5R)-4-(Allyloxy)-5-((R)-hydroxy(phenyl)methyl)-tetrahydrofuran-2,3-diolC14H18O5[α]D = +38.6 (c 0.5, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (3R,4R,5R),5R

(4S,5R,6R,7R,E)-Methyl 5-(allyloxy)-4,6,7-trihydroxy-7-phenylhept-2-enoateC17H22O6[α]D = −17.1 (c 1.6, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (4S,5R,6R,7R)

(1R,2R)-1-((2R,3S)-3-Hydroxy-3,6-dihydro-2H-pyran-2-yl)-2-phenylethane-1,2-diolC13H16O4[α]D = +62.3 (c 0.32, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (1R,2R), 1(2R,3S)

(2E,2′E)-((1R,2R)-1-((2R,3S)-3-(Cinnamoyloxy)-3,6-dihydro-2H-pyran-2-yl)-2-phenylethane-1,2-diyl) bis(3-phenylacrylate)C40H34O7[α]D = +297.1 (c 0.9, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (1R,2R), 1(2R,3S)

(3aR,5R,6S,6aS)-6-(Allyloxy)-5-((R)-hydroxy(phenyl)methyl)-tetrahydro furo[3,2-b]furan-2(5H)-oneC16H18O5[α]D = +18.4 (c 0.81, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (3aR,5R,6S,6aS),5R

(R)-((2R,3S,3aS,6aR)-3-(Allyloxy)-5-oxo-hexahydrofuro[3,2-b]furan-2-yl)(phenyl) methyl cinnamateC25H24O6[α]D = +233.5 (c 0.4, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: R,(2R,3S,3aS,6aR)

(3aR,5R,6S,6aR)-5-((R)-Hydroxy(phenyl)methyl)-2,2-dimethyl-tetrahydro furo[2,3-d][1,3]dioxol-6-olC14H18O5[α]D = −56.2 (c 0.72, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (3aR,5R,6S,6aR),5R

(3aR,5R,6S,6aR)-5-((S)-Hydroxy(phenyl)methyl)-2,2-dimethyl-tetrahydro furo[2,3-d][1,3]dioxol-6-olC14H18O5[α]D = +31.2 (c 0.35, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (3aR,5R,6S,6aR),5S

(R)-((3aR,5S,6S,6aR)-6-Hydroxy-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)(phenyl)methyl cinnamateC23H24O6[α]D = +116.0 (c 0.51, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: R, (3aR,5S,6S,6aR)

(R)-((3aR,5S,6S,6aR) 3-Phenyl-acrylic acid [2,2-dimethyl-6-(3-phenyl-acryloyloxy)-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-phenyl-methyl esterC32H30O7[α]D = −297.1 (c 0.23, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: R, (3aR,5S,6S,6aR)

(R)-((2R,3R,4R)-3-(Allyloxy)-4,5-dihydroxy-tetrahydrofuran-2-yl)(phenyl)methyl cinnamateC23H24O6[α]D = +114.9 (c 0.77, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: R, (2R,3R,4R)

(4S,5R,6R,7R,E)-Ethyl 5-(allyloxy)-7-(cinnamoyloxy)-4,6-dihydroxy-7-phenylhept-2-enoateC27H30O7[α]D = +129.4 (c 0.51, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (4S,5R,6R,7R)

(1R,2R)-2-Hydroxy-2-((2R,3S)-3-hydroxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)-1-phenylethyl cinnamateC22H22O5[α]D = +166.2 (c 0.1, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: (1R,2R), 2(2R,3S)

(R)-((4R,4aR,8aS)-2,2-Dimethyl-4,4a,6,8a-tetrahydropyrano[3,2-d][1,3]dioxin-4-yl)(phenyl)methyl cinnamateC25H26O5[α]D = +243.5 (c 0.5, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: R, (4R,4aR,8aS)

(R)-((4R,4aR,8aS)-2,2-Dimethyl-6-oxo-4,4a,6,8a-tetrahydropyrano[3,2-d][1,3] dioxin-4-yl)(phenyl)methyl cinnamateC25H24O6[α]D = +200.1 (c 0.1, CHCl3)Source of chirality: d-glucose and asymmetric synthesisAbsolute configuration: R, (4R,4aR,8aS)