METHODS FOR PREPARING ANTIVIRAL CALANOLIDE COMPOUNDS

摘要

The present invention relates to methods for preparing 2,2-dimethyl-5-acyloxy-10-propyl-2H,8H-benzo[1,2-b:3,4-b']dipyran-8-one (5) and 2,2-dimethyl-5-hydroxy-10-propyl-2H,8H-benzo[1,2-b:3,4-b']dipyran-8-one (6) and their use as intermediates for the synthesis of antiviral calanolide compounds. For example, Fries rearrangement on compound 5 or Friedel-Crafts reaction on 6, yields intermediate 2,2-dimethyl-5-hydroxy-6-propionyl-10-propyl-2H,8H-benzo[1,2-b:3,4-b']dipyran-8-one (4), which, in turn, can be converted to (+)-calanolide A and (-)-calanolide B. The coupling of compound 6 with the appropriate chiral molecule under Mitsunobu or nucleophilic displacement leads to the asymmetric synthesis of antiviral calanolide compounds.