Host: Division of Organic Chemistry, The Pharmaceutical Society of Japan
Pages 74-75
Calophyllum coumarins (Guttiferae) are strongly active against HIV-1, in which (+)-calaonolide A (1) and (+)-inophyllum B (2) are candidates for AIDS drugs. We had succeeded in the enantioselective total synthesis of (+)-1 through (−)-quinine-catalyzed intramolecular oxo-Michael-type addition (IMA) reaction as a key step; however, utilization of protecting (TIPS) group was necessary. Now we established enantioselective short-course synthesis of (+)-1 and (+)-2 without any additional protecting groups. Demethylation and thermodynamic isomerization of optically active cis-methoxypyranocoumarin with MgI2 gave a 1:1 mixture of cis- and trans-hydroxypyranocoumarins without loss of optical purity. After separation, trans-derivative was subjected to chromene formation followed by stereoselective reduction to give a desired coumarin. Thus, (+)-2 and (+)-1 were obtained in total 5.1% and 15.2% yield, respectively, with 8 steps.
