Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-08-02
2000-03-28
Owens, Amelia
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
549277, 549278, 549282, A61K 3135, C07D40700
Patent
active
060432713
ABSTRACT:
A method of preparing (.+-.)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (.+-.)-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (.+-.)-calanolide A. A method for resolving (.+-.)-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing a viral infections using (.+-.)-calanolide or (-)-calanolide is provided.
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Boulanger William A.
Chen Wei
Flavin Michael T.
Khilevich Albert
Kucherenko Alla
Owens Amelia
Sarawak MediChem Pharmaceuticals, Inc.
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