The first simple and efficient synthesis of the unusual dipeptide part of Phomopsin A

A practical high yielding synthesis of the key halogenated dipeptide part of Phomopsin A 2 is reported. The key steps are a selective Heck coupling, a Sharpless asymmetric dihydroxylation in PEG and a benzoyl isocyanate mediated synthesis of dehydrovaline.

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Ethyl (2R,3S)-3-[4-(benzyloxy)-3-bromo-5-chlorophenyl]-2,3-dihydroxypropanoateC18H18BrClO5Ee ⩾98%[α]D25=+9.8 (c 1.0, MeOH)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

Ethyl (2R,3S)-3-[4-(benzyloxy)-3-bromo-5-chlorophenyl]-3-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}propanoateC25H24BrClO7S[α]D25=+36.8 (c 2.5, MeOH)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2R,3S)

Ethyl (2S,3S)-2-azido-3-[4-(benzyloxy)-3-bromo-5-chlorophenyl]-3-hydroxypropanoateC18H17BrClN3O4[α]D25=+65.2 (c 1.0, MeOH)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3S)

Ethyl (2S,3S)-3-[4-(benzyloxy)-3-bromo-5-chlorophenyl]-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropanoateC23H27BrClNO6[α]D25=+2.5 (c 1.0, MeOH)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (2S,3S)

[(2S)-3,3-Dimethyloxiran-2-yl]methanolC5H10O2[α]D25=-18.0 (c 2.0, CHCl3)Source of chirality: asymmetric epoxidationAbsolute configuration: (2S)

1-Methyl-1-[(4R)-2-oxo-1,3-oxazolidin-4-yl]ethyl benzoateC13H15NO4[α]D25=+12.3 (c 1.0, MeOH)Source of chirality: asymmetric epoxidationAbsolute configuration: (4R)

tert-Butyl [(1R)-2-hydroxy-1-(hydroxymethyl)-2-methylpropyl]carbamateC10H21NO4[α]D25=+2.7 (c 1.0, MeOH)Source of chirality: asymmetric epoxidationAbsolute configuration: (1R)

tert-Butyl (4R)-4-(1-hydroxy-1-methylethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylateC13H25NO4[α]D25=+22.9 (c 1.0, MeOH)Source of chirality: asymmetric epoxidationAbsolute configuration: (4R)

tert-Butyl (4S)-4-isopropenyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylateC13H23NO3[α]D25=+16.9 (c 1.2, MeOH)Source of chirality: asymmetric epoxidationAbsolute configuration: (4S)

Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbut-3-enoateC11H19NO4[α]D25=+37.5 (c 1.0, MeOH)Source of chirality: asymmetric epoxidationAbsolute configuration: (2S)

Methyl (2S)-2-{[(2S,3S)-3-[4-(benzyloxy)-3-bromo-5-chlorophenyl]-3-hydroxy-2-[(tert-butoxycarbonyl)amino]propanoyl]amino}-3-methylbut-3-enoateC37H32BrClN2O7[α]D25=+16.9 (c 1.75, MeOH)Source of chirality: asymmetric synthesis