16 巻 (2017) 4 号 p. 102-105
The (−)-podophyllic aldehydes (Figure 1) exhibit notable antineoplastic cytotoxicity by apoptosis-inducing activities. In this study, we analyzed the selectivity mechanisms of some important reactions in the asymmetric total synthesis of (+)-podophyllic aldehydes which are enantiomers of the (−)-podophyllic aldehydes, by the molecular orbital method. As a result, it was shown that the selectivity of the Grignard reaction in compound 1 (Figure 2) is caused by steric hindrance. Furthermore, it was also indicated that the selectivity of the reduction in compound 2–1 is caused by the localization of LUMO at the reactive site, and the reduction in compounds 2–2 and 2–3 Scheme 2) does not proceed due to the steric hindrance by the trimethoxyphenyl group.