Total Syntheses Of Alopecuridine, Sieboldine A,and Lycojapodine A

Lycopodium alkaloids are a large group of structurally complex natural products. Over200this type alkaloids have been isolated up to date. Owing to their intricate polycyclic structures and potential biological activities, these compounds have received considerable attention from the synthetic chemists. This dissertation describes the total synthesis of three important nature products among the fawcettimine type lycopodium alkaloids in three parts.1. The first chapter introduced the isolation of lycopodium alkaloids and how these compounds are divided into four categories based on their structural features. The total synthesis along with the possible biogenetic relationships of fawcettimine type alkaloids were also summarized in detail.2. Our racemic total synthesis of alopecuridine, sieboldine A, and lycojapodine A are fully described. After examing the three alkaloids from a structural point of view, we envisioned a retro-synthetic analysis of target molecules with a biomimetic strategy. In this novel route, alopecuridine was firstly synthesized in13steps, which featured a semipinacol rearrangement of medium-sized ring and an intramolecular pinacol coupling. Then, a one-pot two steps biomimetic oxidation procedure was realized to transform alopecuridine into sieboldine A. In the course of our exploration on the synthesis of lycojapodine A, many designed approaches were attempted but failed. It turns out that the biomimetic transformation from alopecuridine could finally generated lycojapodine A.3. Based on our racemic synthetic process, we redesigned our route to benefit the asymmetric synthesis and accomplished the total synthesis of (+)-alopecuridine,(+)-sieboldine A and (-)-lycojapodine A from kown chiral compound.