Reassigning the stereochemistry of bioactive cepharanthine using calculated versus experimental chiroptical spectroscopies

The absolute configuration of cepharanthine (1), a strongly bioactive bisbenzylisoquinoline alkaloid exhibiting 12 specific bioactivities without any reported negative side-effects, has been reassigned from (1R,1′S) to (1R,1′R) using quantum theory. The absolute configurations (ACs) of 13 other analogues of 1 were also systematically reassigned. Six quaternary salts were prepared from 1 and one exhibited strong anti-bacterial activity against Bacillus subtilis with MIC 0.31 μM, while Ciprofloxacin, the positive control medicine was 3.88 μM. This work established the critical importance of correlating chiroptical experimental spectra with their quantum mechanically predicted spectra for accurate stereogenic center assignments.