Loading patent…
AssigneeSarawak MediChem Pharmaceuticals, Inc.
InventorsMichael T. Flavin, Ze-Qi Xu, John D. Rizzo, Albert Khilevich, Abram Kivovich Sheinkman
Estimating the term…
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 viral infections using (.+-.)-calanolide A or (-)-calanolide A is provided.
A method for preparation of chromanone 7 ##STR4## comprising cyclization of aldol product 7b ##STR5## in the presence of an acid or in the presence of an azo compound and a phosphorus derivative.
A method of preparation of chromanone 7 ##STR6## comprising treating cis-chromanone 7a ##STR7## with a base so as to form chromanone 7.
Dependencies are inferred from the claim text.