Enantioselective synthesis of a potential key intermediate for the total synthesis of fumagillin

Key intermediate, 7, of a projected total synthesis of the anti-angiogenesis compound Fumagillin1 and the semi-synthetic analogue TNP-4702, has been prepared in enantiomerically pure form by employing an early nucleophilic addition ring closure [NARC] sequence to construct the cyclohexene backbone.

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(+)-(2S)-N-[(2S,3R)-2-(Ethenyl)-3-(hydroxy)-6-heptenoyl]bornane-10,2-sultamC19H29NO4SEe, de >95% (NMR)[α]D24=+95.35 (c 1.30, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(+)-(2S)-N-[(1R,2S)-1-Hydroxy-3-cyclohexen-2-carbonyl]bornane-10,2-sultamC17H25NO4SEe, de >95% (NMR)[α]D24=+270.0 (c 0.70, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)

(+)-(1S,2R)-2-Hydroxy-5-cyclohexenecarboxylic acidC7H10O3Ee, de >95% (NMR)[α]D22=+95.45 (c 4.00, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(+)-(2S)-N-[(1R,2S)-1-(((tert-Butyldiphenyl)silyl)oxy)-3-cyclohexen-2-carbonyl]bornane-10,2-sultamC33H43NO4SSiEe, de >95% (NMR)[α]D22=+81.0 (c 0.20, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)

(+)-(2S)-N-[(1R,2R,3S,4R)-1-(((tert-Butyldiphenyl)silyl)oxy)-3,4-(dihydroxy)cyclo-hexan-2-carbonyl]bornane-10,2-sultamC33H45NO6SSiEe, de >95% (NMR)[α]D22=+5.4 (c 0.73, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R,3S,4R)

(+)-(2S)-N-[(3aS,4S,5R,7aR)-2,2-Dimethyl-5-(((tert-butyldiphenyl)silyl)oxy)hexahydro[1,3]benzodioxol-4-carbonyl]bornane-10,2-sultamC36H49NO6SSiEe, de >95% (NMR)[α]D24=+8.2 (c 1.00, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (3aS,4S,5R,7aR)

(+)-(1S,2R)-2-(Hydroxy)-5-cyclohexenecarboxylic acid (N-methoxy-N-methyl)amideC9H15NO3Ee, de >95% (NMR)[α]D23=+108.94 (c 7.50, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(+)-(1S,2R)-2-(((tert-Butyldiphenyl)silyl)oxy)-5-cyclohexenecarboxylic acid (N-methoxy-N-methyl)amideC25H33NO3SiEe, de >95% (NMR)[α]D24=+83.6 (c 1.95, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

(−)-(1S,2S,3R,6R)-2,3-(Dihydroxy)-6-(((tert-butyldiphenyl)silyl)oxy)cyclohexane-carboxylic acid (N-methoxy-N-methyl)amideC25H35NO5SiEe, de >95% (NMR)[α]D24=-17.95 (c 2.00, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S,3R,6R)

(−)-(3aS,4S,5R,7aR)-5-(((tert-Butyldiphenyl)silyl)oxy)-2,2-dimethyl-hexahydro-[1,3]benzodioxol-4-carboxylic acid (N-methoxy-N-methyl)amideC28H39NO5SiEe, de >95% (NMR)[α]D24=-84.1 (c 1.00, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (3aS,4S,5R,7aR)

(−)-(3aS,4S,5R,7aR)-4-Acetyl-5-(((tert-butyldiphenyl)silyl)oxy)-2,2-dimethylhexahydro-[1,3]benzodioxoleC27H36O4SiEe, de >95% (NMR)[α]D25=-74.9 (c 1.25, chloroform)Source of chirality: asymmetric synthesisAbsolute configuration: (3aS,4S,5R,7aR)