Method for the preparation of aldol product 7B

Details Method for the preparation of aldol product 7B Method for the preparation of aldol product 7B

1997-09-09

1998-11-24

Owens, Amelia

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D49300

Patent

active

058409211

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 viral infections using (.+-.)-calanolide A or (-)-calanolide A is provided.

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