Studies On The Syntheses Of Polycyclic Alkaloids

The total synthesis of alkaloids is one of the important fields of organic chemistry. This thesis finished some studies towards the total synthesis of bioactive polycyclic alkaloids, and correspondingly a series of importantly progressive results were achieved. This thesis consists of the following four parts:1. A concise and efficient total synthesis of stemonamine was achieved for the first time in 13 steps from the known compound 1-57 in an overall yield of 3.7%, featuring a tandem semipinacol rearrangement/Schmidt reaction and a Dieckmann condensation.2. Simple and efficient formal total syntheses of stemonamine and cephalotaxine were achieved via a facile intramolecular Schmidt reaction of symmetric azido dione precursor. By use of this key reaction, known intermediate 2-44 and 2-56 were obtained through limited chemical transformation. This concise Schmidt reaction may be applicable in other alkaloids syntheses.3. A new one-pot procedure for the synthesis of aminoenone from chloroalkyl enone and sodium azide was designed and demonstrated. Two type's substrates (aryl chloroalkyl enones and non-aryl chloroalkyl enones) were investigated. Meanwhile, we found that reaction temperature has a strong effect on reaction product. A presumed triazoline intermediate in this reaction process was obtained and confirmed by a single-crystal X-ray analysis for the first time. As the application of this methodology, the formal synthesis of polycyclic alkaloid hexahydroapoerysopine and cephalotaxine were also achieved through limited normal chemical transformation.4. Synthetic studies on the asymmetric total synthesis of morphine. By use of semipinacol rearrangement, we have made an attempt to constract the key quaternary unit in morphine. Despite, we could not obtain the desired rearrangement precursor, this investigation made us have a further understand on the synthesis of this alkaloid.