A convenient procedure for the synthesis of chiral 6,7-dihydroxy-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones

The cyclocondensation reactions between l-α-amino acid phenylhydrazides and 2,3-O-isopropylidene-l-erythruronolactone in the presence of a catalytic amount of p-toluenesulfonic acid afforded diastereomerically pure (3S,6R,7R,7aS)-3-substituted-6,7-isopropylidenedioxy-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones, which were converted by acidic hydrolysis with MeOH–HCl into their corresponding optically active (3S,6R,7R,7aS)-3-substituted-6,7-dihydroxy-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones in good yields.

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(3S,6R,7R,7aS)-6,7-Dihydroxy-3-methyl-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-dioneC13H15N3O4De 99%[α]D25=+14.7 (c 1.12, MeOH)Source of chirality: starting materialsAbsolute configuration: (3S,6R,7R,7aS)

(3S,6R,7R,7aS)-3-Benzyl-6,7-dihydroxy-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-dioneC19H19N3O4De 99%[α]D25=+19.2 (c 1.15, MeOH)Source of chirality: starting materialsAbsolute configuration: (3S,6R,7R,7aS)

(3S,6R,7R,7aS)-6,7-Dihydroxy-3-hydroxymethyl-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-dioneC13H15N3O5De 99%[α]D25=-33.8 (c 0.94, MeOH)Source of chirality: starting materialsAbsolute configuration: (3S,6R,7R,7aS)

(3S,6R,7R,7aS)-6,7-Dihydroxy-3-(2-methylthioethyl)-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-dioneC15H19N3O4De 99%[α]D25=+24.4 (c 0.96, MeOH)Source of chirality: starting materialsAbsolute configuration: (3S,6R,7R,7aS)

(3S,6R,7R,7aS)-6,7-Dihydroxy-3-isopropyl-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-dioneC15H19N3O4De 99%[α]D25=-20.5 (c 0.61, MeOH)Source of chirality: starting materialsAbsolute configuration: (3S,6R,7R,7aS)

(3S,6R,7R,7aS)-6,7-Dihydroxy-3-isobutyl-1-phenylamino-dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-dioneC16H21N3O4De 99%[α]D25=+32.0 (c 0.46, MeOH)Source of chirality: starting materialsAbsolute configuration: (3S,6R,7R,7aS)