Method for the preparation of (+)-calanolide A and analogues thereof
摘要
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.
申请公布号
US5977385(A)
申请公布日期
1999.11.02
申请号
US19980115984
申请日期
1998.07.15
申请人
SARAWAK MEDICHEM PHARMACEUTICALS
发明人
FLAVIN, MICHAEL T.;XU, ZE-QI;KHILEVICH, ALBERT;ZEMBOWER, DAVID;RIZZO, JOHN D.;LIAO, SHUYUAN;MAR, AYE;LIN, LIN;VILAYCHACK, VILAYPHONE;BRANKOVIC, DARKO;DZEKHSTER, SERGEY;LIU, JINJUN