Enantioselective access to a versatile 4-oxazolidinonecarbaldehyde and application to the synthesis of a cytotoxic jaspine B truncated analogue

The preparation of the versatile aldehyde 15 via a concise route based on a formal anti-asymmetric aminohydroxylation and its use in a 5-step synthesis of a cytotoxic C12 analogue of the natural anhydrophytosphingosine jaspine B is presented.

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(2S,3S)-3-Benylamino-4-(benzyloxy)propan-1,2-diolC18H23NO3Ee = 90%[α]D20=+28.0 (c 1.40, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)

(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-(hydroxymethyl)-2-oxazolidinoneC19H21NO4Ee = 90%[α]D20=+27.5 (c 1.30, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-(formyl)-2-oxazolidinoneC19H19NO4Ee = 90%[α]D20=+11.0 (c 2.20, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1R)-1-(hydroxyoctyl)]-2-oxazolidinoneC27H37NO4Ee = 90%[α]D20=+26.4 (c 1.65, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1R)-1-hydroxy-2-(heptynyl)]-2-oxazolidinoneC26H31NO4Ee = 90%[α]D20=+22.0 (c 1.32, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1R)-1-(methanesulfonyloxyoctyl)]-2-oxazolidinoneC28H39NO6SEe = 90%[α]D20=+26.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(3aS,6S,6aS)-3-Benzyl-6-octyltetrahydrofuro[3,4-d][1,3]oxazol-2(3H)-oneC20H29NO3Ee = 90%[α]D20=+69.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aS,6S,6aS)

(3aS,6S,6aS)-6-Octyltetrahydrofuro[3,4-d][1,3]oxazol-2(3H)-oneC13H23NO3Ee = 90%[α]D20=+77.7 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aS,6S,6aS)

(2S,3S,4S)-4-Amino-2-(octyl)tetrahydrofuran-3-olC12H25NO2Ee = 90%[α]D20=+20.0 (c 0.5 CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,4S)