A carbohydrate approach for the formal total synthesis of the prostacyclin analogue (16S)-iloprost

The formal total synthesis of the synthetic and stable analogue of prostacyclin, (16S)- iloprost is described via a convergent synthesis starting from readily available d-glucose. Julia olefination and the aldol reaction are the key steps involved in the synthesis.

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(3aR,5S,6R,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxoleC13H22O5[α]D20=+36 (c 1.0, CHCl3)Source of chirality: d-GlucoseAbsolute configuration: (3aR,5S,6R,6aR)-5-((R)

(R)-1-((3aR,5S,6R,6aR)-2,2,6-Trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)ethane-1,2-diolC10H18O5[α]D25=+22 (c 2.0, CHCl3)Source of chirality: d-GlucoseAbsolute configuration: (R)-1-(3aR,5S,6R,6aR)

((3aR,5S,6R,6aR)-2,2,6-Trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methanolC9H16O4[α]D25=+29.2 (c 2.5, MeOH)Source of chirality: d-GlucoseAbsolute configuration: (3aR,5S,6R,6aR)

tert-Butyldiphenyl(((3aR,5S,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methoxy)silaneC25H34O4Si[α]D25=+7.8 (c 2.9, MeOH).Source of chirality: d-GlucoseAbsolute configuration: (3aR,5S,6R,6aR)

(2S,3S)-4-((tert-Butyldiphenylsilyl)oxy)-2-methylbutane-1,3-diolC21H30O3Si[α]D25=+10.9 (c 2.4, MeOH)Source of chirality: d-GlucoseAbsolute configuration: (2S, 3S)

(6S,7S)-6-(Methoxymethoxy)-2,2,7,10,10,11,11-heptamethyl-3,3-diphenyl-4,9-dioxa-3,10-disiladodecaneC29H48O4Si2[α]D20=-12.9 (c 1, CHCl3)Source of chirality: d-GlucoseAbsolute configuration: (6S,7S)

(2S,3S)-4-((tert-Butyldiphenylsilyl)oxy)-3-(methoxymethoxy)-2-methylbutyl 4-methylbenzenesulfonateC30H40O6SSi[α]D25=+3.4 (c 2.5, MeOH)Source of chirality: d-GlucoseAbsolute configuration: (2S,3S)

(S)-5-((S)-Hex-4-yn-2-yl)-9,9-dimethyl-8,8-diphenyl-2,4,7-trioxa-8-siladecaneC26H36O3Si[α]D25=-12.8 (c 1.0, MeOH)Source of chirality: d-GlucoseAbsolute configuration: (5S,6S)

(2S,3S)-2-(Methoxymethoxy)-3-methylhept-5-yn-1-olC10H18O3[α]D25=-15.2 (c 1.2, MeOH)Source of chirality: d-GlucoseAbsolute configuration: (2S,3S)

(3a′S,4′R,5′R,6a′R)-4′-((3S,4S,E)-3-(Methoxymethoxy)-4-methyloct-1-en-6-yn-1-yl)-5,5-dimethylhexahydro-1′H-spiro[[1,3]dioxane-2,2′-pentalen]-5′-olC24H38O5[α]D25=+2.8 (c 0.49, MeOH)Source of chirality: d-GlucoseAbsolute configuration: (3a′S,4′R,5′R,6a′R)-4′-((3S,4S,E)

(3aS,4R,5R,6aR)-5-Hydroxy-4-((3S,4S,E)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl)hexahydropentalen-2(1H)-oneC17H24O3[α]D25=+9.0 (c 1.0, MeOH)Source of chirality: d-GlucoseAbsolute configuration: (3aS,4R,5R,6aR)