Tetrahydroprotoberberine alkaloids have good bioactivity against malaria and epilepsy, among them, xylopinine has good anti malaria activity, while laudanosine has epilepsy treatment activity. A concise asymmetric synthesis of (S)-(－)xylopinine and (S)-(＋)-laudanosine has been reported. The key strategies include diastereoselective nucleophilic addition to N-tert-butanesulfinimine, which is combined with Pictet-Spengler reaction as a key step for constructing the pivotal tetrahydroprotoberberine skeleton. This strategy provides a concise and rapid approach to (S)-(－)-xylopinine (7 steps and 11.1% overall yield) and (S)-(＋)-laudanosine (7 steps and 16.4% overall yield) from known starting materials. The S configuration of synthetic xylopinine and laudanosine at C(14) is confirmed by comparing their specific rotation data. © 2023 Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.