SHORT CHEMICAL SYNTHESIS OF (-)-CHORISMIC ACID FROM (-)-SHIKIMIC ACID

A short and efficient partial synthesis of (-)-chorismic acid (1) from (-)-shikimic acid (4) is reported. Chorismate is the key branch-point intermediate in the shikimic acid pathway, which bacteria, fungi, and lower plants use to biosynthesize inter alia the amino acids phenylalanine, tyrosine, and tryptophan as well as the isoprenoid quinones and folate coenzymes. Reaction of (-)-methyl shikimate ((-)-5) with 2-acetoxyisobutyryl bromide (acetonitrile, 0 °C, 30 min) afforded (+)-methyl (3R,4S,5R)-3-bromo-4-acetoxy-5-hydroxy-1-cyclohexene-1-carboxylate ((+)-7) in 76-85% yield. Transesterification of this bromoacctate with NaOCH3 (1.05 equiv, CH3OH, 0 °C, 30 min) led quantitatively to the corresponding epoxyol, (+)-methyl 3,4-anhydroshikimate (10). Payne rearrangement of this trans-epoxyol (NaOCH3-CH3OH, 50 °C, 10 min) produced (-)-methyl (3S,4S,5R)-3-hydroxy-4,5-epoxy-1-cyclohexene-1-carboxylate ((-)-2), which has previously been converted into (-)-chorismic acid. This shikimate to chorismate transformation constitutes the first synthetic interconversion paralleling the biogenetic relationship shared by these two metabolites. © 1990, American Chemical Society. All rights reserved.