Synthetic Studies on Potent Marine Drugs : Synthesis and the Crystal Structure of 6-tert-butyl-4-phenyl-4H-chromene-2-carboxylic Acid

Abstract EN

4H-Chromene-2-carboxylic acid ester derivatives of renieramycin M might be of use for the structural-activity relationship studies of antitumor antibiotic tetrahydroisoquinoline natural products.

Accordingly, 6-tert-butyl-4-phenyl-4H-chromene-2-carboxylic acid, one key intermediate, was synthesized via the condensation of (3E)-2-oxo-4-phenylbut-3-enoate methyl ester with 4-tert-butylphenol in the presence of AuCl3/3AgOTf (5 mol%), followed by cyclodehydration and aqueous hydrolysis.

The product was unambiguously shown to the 4H-chromene-2-carboxylic acid by spectroscopy and X-ray crystallographic analysis.

A packing diagram of the crystal structure shows that aromatic π-stacking interactions and O–H⋯O hydrogen bond stabilize the structure in the solid.