McDonnell, Boehnen, Hulbert & Berghoff
Method for the preparation of (+)-calanolide A and analogues thereof
 A method of preparing (+)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. According to the disclosed method, chromene 4 intermediate was subjected to a chlorotitanium-mediated aldol reaction with acetaldehyde to selectively produce (.+-.)-8a. Separation and enzyme-mediated resolution of (.+-.)-8a produced (+)-8a. Cyclization of (+)-8a under neutral Mitsunobu conditions followed by Luche reduction of (+)-7 produced (+)-calanolide A in high yield and enantiomeric purity. The method of the invention has been extended to produce potent antiviral calanolide A analogues. 
Sarawak MediChem Pharmaceuticals
C C A C
C07D C07D A61K C07D
inventional inventional inventional inventional
Lin Darko Jinjun John D. Ze-Qi Shuyuan Sergey Aye Vilayphone Michael T. Albert David
Lin Brankovic Liu Rizzo Xu Liao Dzekhster Mar Vilaychack Flavin Khilevich Zembower