Phenolate → 7-beta-Galactopyranosyloxycoumarin-4-acetic acid

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Reaction Steps

In accordance with exemplary Scheme 1, the carboxy function of 7-Hydroxycoumarin-4-acetic acid 1 (available from Aldrich Chemical Co., Milwaukee, Wis.) is protected by, for example, conversion to the methyl ester 2 via the Fischer Spier reaction using a procedure described by Baker, W., Haksar, C. N., McOmie, J. F. W., J. Chem. Soc. 170-173 (1950). An enzyme cleavable group can then be added to the remaining hydroxyl function at the 7 position. For example, β-D-galactopyranoside tetraacetate 3 is prepared by reaction of the phenolate anion of compound 2 with tetra-O-acetyl-α-D-galactopyranosyl bromide (available from Sigma Chemical Co., St. Louis, Mo.) using a procedure described by Baggett et al. in Carbohydrate Research 197, 295-301, (1990). The protected species then can be deprotected. As shown in Scheme 1, 7-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyloxy)coumarin-4-acetate 3 is hydrolysed to give 7-β-D-galactopyranosyloxycoumarin-4-acetic acid 4 using the procedure described by Baggett et al. in Carbohydrate Research 197, 295-301, (1990). Compound 4 can then be modified with a suitable amine functional group to yield the final product. Scheme 1 demonstrates conversion of compound 4 to the pentafluorophenyl ester and then reaction with ethanolamine to give the compound 5. Compound 5 can also be obtained from compound 3 as outlined in Scheme 1.

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