Sarawak Medichem Pharmaceuticals, Inc.

Ailing Li

Ze-Qi Xu

Raghu Samy

Hongwei Yuan

Hua Cao

Jennifer Crabb

The present invention relates to methods for preparing 2,2-dimethyl-5-acyloxy -10-propyl-2H,8H-benzo&lsqb;1,2-b:3,4-b&prime;&rsqb;dipyran-8-one (5) and 2,2-dimethyl-5-hydroxy-10 -propyl-2H,8H-benzo&lsqb;1,2-b:3,4-b&prime;&rsqb;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&lsqb;1,2-b:3,4-b&prime;&rsqb;dipyran-8-one (4), which, in turn, can be converted to (&plus;)-calanolide A and (&minus;)-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.

Methods for preparing antiviral calanolide compounds

The present invention relates to methods for preparing 2,2-dimethyl-5-acyloxy-10-propyl-2H,8H-benzo&lsqb;1,2-b:3,4-b&prime;&rsqb;dipyran-8-one (5) and 2,2-dimethyl-5-hydroxy-10-propyl-2H,8H-benzo&lsqb;1,2-b:3,4-b&prime;&rsqb;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&lsqb;1,2-b:3,4-b&prime;&rsqb;dipyran-8-one (4), which, in turn, can be converted to (&plus;)-calanolide A and (&minus;)-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.

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Ailing Li