Practical and highly stereoselective approaches to the total synthesis of (−)-codonopsinine

The enantiopure total synthesis of (−)-codonopsinine is described using two effective chiron approaches starting either from commercially available l-xylose or from readily available Garner aldehyde. The key steps included Julia trans-olefination, highly diastereoselective alkylation and cascade epoxidation–cyclization strategies.

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6-Hydroxy-2,2-dimethyl-5-(4-methylphenylsulfonyloxymethyl)-(3aS,5S,6R,6aS)-perhydrofuro[2,3-d][1,3]dioxoleC15H20O7S[α]D20=+13.8 (c 1.0, CH3OH)Source of chirality:l-xyloseAbsolute configuration:(3aS,5S,6R,6aS)

2,2,5-Trimethyl-(3aS,5S,6R,6aS)-perhydrofuro[2,3-d][1,3]dioxol-6-olC8H14O4[α]D20=+22.4 (c 1.0, CH3OH)Source of chirality:l-xyloseAbsolute configuration:(3aS,5S,6R,6aS)

6-Hydroxy-2,2-dimethyl-5-(4-methylphenylsulfonyloxymethyl)-(3aS,5S,6R,6aS)-perhydrofuro[2,3-d][1,3]dioxoleC16H22O5[α]D20=+20.3 (c 1, CH3OH)Source of chirality:l-xyloseAbsolute configuration:(3aS,5S,6R,6aS)

2-(4-Methoxybenzyloxy)-4-(4-methoxyphenyl)-1-methyl-(1S,2S,3E)-3-butenyl formateC21H24O5[α]D20=+17.7 (c 1.0, CH3OH)Source of chirality:l-xyloseAbsolute configuration:(1S,2S,3E)

3-(4-Methoxybenzyloxy)-5-(4-methoxyphenyl)-(2S,3S,4E)-4-penten-2-olC20H24O4[α]D20=+74.7 (c 1.1, CH3OH)Source of chirality:l-xyloseAbsolute configuration:(2S,3S,4E)

1-[4-Azido-3-(4-methoxybenzyloxy)-(E,3S,4R)-1-pentenyl]-4-methoxybenzeneC20H23N3O3[α]D20=+70.2 (c 0.5, MeOH)Source of chirality:l-xyloseAbsolute configuration:(E,3S,4R)

4-Azido-1-(4-methoxyphenyl)-(E,3S,4R)-1-penten-3-olC12H15N3O2[α]D20=+17.1 (c 0.8, MeOH)Source of chirality: l-xyloseAbsolute configuration: (E,3S,4R)

2-[tert-Butoxy carbonylamino]-(2R,3S,4E)-5-(4-methoxyphenyl)-pent-4-en-3-olC17H25NO4[α]D20=-12.6 (c 0.5, MeOH)Source of chirality: l-xylose or d-serineAbsolute configuration: (2R,3S,4E)

tert-Butyl 3,4-dihydroxy-2-(4-methoxyphenyl)-5-methyl-(2R,3R,4R,5R)-tetra hydro-1H-1-pyrrolecarboxylateC17H25NO5[α]D20=-50.2 (c 1, MeOH)Source of chirality: l-xylose or d-serineAbsolute configuration: (2R,3R,4R,5R)

tert-Butyl 4-[1-hydroxy-3-(4-methoxyphenyl)-(1S)-2-propynyl]-2,2-dimethyl-(4R)-1,3-oxazolane-3-carboxylateC20H27NO5[α]D20=+26.8 (c 1.4, MeOH)Source of chirality: d-serineAbsolute configuration: (1S,4R)

tert-Butyl 4-[1-hydroxy-3-(4-methoxyphenyl)-(1S,2E)-2-propenyl]-2,2-dimethyl-(4R)-1,3-oxazolane-3-carboxylateC20H29NO5[α]D20=-15.1 (c 1.9, MeOH)Source of chirality: d-serineAbsolute configuration: (1S,2E,4R)

2-[tert-Butylcarbonylamino]-(2R,3S,4E)-5-(4-methoxyphenyl)-pent-4-ene-1,3-diolC17H25NO5[α]D20=-20.2 (c 1.4, CH3OH)Source of chirality: d-serineAbsolute configuration: (3aS,5S,6R,6aS)