Sarawak Medichem Pharmaceuticals, Inc.

Aye Mar

Michael T Flavin

Ze-Qi Xu

John D Rizzo

Albert Khilevich

Lin Lin

David Zembower

Shuyuan Liao

Darko Brankovic

Jinjun Liu

Sergey Dzekhster

Vilayphone Vilaychack

Vilayphone Vilaychak

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.

Method for the preparation of (+)-calanolide A and analogues thereof

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.

(+)-calanolide A and analogues thereof

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Chicago, IL, United States of America

Aye Mar