Studies Towards The Total Synthesis Of Daphniyunnine

In this thesis, total synthesis of the Daphniyunnine as the target, two synthetic strategies of Daphniyunnine were designed to build the skeleton of them by intramolecular Diels-Alder reaction of furans (IMDAF) reaction and Prins-pinacol rearrangement reaction as key steps respectively. In the process of the study, new methodologies of Prins cyclization were developed. The thesis mainly consists of the following three chapters:Chapter 1. Progress of Daphniphyllum Alkaloids was reviewed.The sources,isolation structure identification bioactiy,biosynthesis,biomimetic total synthesis and chemical synthesis of Daphniphyllum Alkaloids were presented systematically in this chapter. Daphniphyllum Alkaloids are structurally diverse group of natural products found in the genus Daphniphyllum (Daphniphyllaceae). These alkaloids have attracted great interest from chemists since Yagi reported the isolation of daphnimacrine firstly in 1909. Suzuki and Yamamura firstly proposed the biosynthesis of Daphniphyllum Alkaloids by feeding experiments of isotope label. At the basis of Suzuki and Yamamura's work, Heathcock proposed the biogenic synthesis hypothesis of Daphniphyllum Alkaloids (Heathcock's hypothesis) and have achieved several alkaloids by biomimetic total synthesis. On chemical synthesis of these alkaloids, building of the skeletons of Daphniphyllum Alkaloids have been reported by Overman Denmark,Bonjoch et al.Chapter 2. Building skeletons of Daphniyunnine by intramolecular Diels-Alder reaction of furansIt was designed to build the carbon ring skeleton of Daphniyunnine A—E by intramolecular Diels-Alder reaction of furans (IMDAF) as key step. In this strategy, (S)-Carvone and furfuryl alcohol as materials, several compounds were obtained to explore the IMDAF reaction under thermodynamic and dynamic conditions. Semiquinone substrates, which were designed in order to activate the dienophile in IMDAF reaction, were synthesized and they became aryl easily under IMDAF conditions. This strategy for the synthesis of Daphniphyllum Alkaloids gained valuable work experience.Chapter 3. Building of the skeletons of Daphniyunnine by Prins-pinacol rearrangement reaction and studies on Prins cyclizationIt was designed to build the carbon ring skeleton of Daphniyunnine B by Prins-pinacol rearrangement as key step. Cyclopentanone as material,2-(4, 4-dimethoxybutyl)-l-alkene substituted cyclopentanols were synthesized and we tried to explore whether they would occur the Prins-pinacol rearrangement reaction promoted by Lewis acid. In the reaction, we found that spiro-compounds were obtained by 3-methoxyprop-l-ene substituent promoted pinacol rearrangement reaction under Lewis acid without Prins cyclization. During the course of synthesizing seven-membered rings by Prins cyclization, some new methodologies evolved. The products of Prins cyclization were obtained by FeCl3-promoted reaction of 2-(4, 4-dimethoxybutyl)-1-alkyne substituted cyclopentanols. FeCl3 was superior to other Lewis acid for this reaction. Then, at the basis of this optimized cyclization conditions, derivatives were studied too. We found thatα,β-unsaturated ketone including seven-membered rings was obtained when aromatic alkyne substituent group was employed, however,1-chloroalkene bicarbocycles was gained when alkyl groups substituted alkyne was employed. In the experiment, we also, found that spiro[4.5]decane derivatives were obtained from 2-(5,5-dimethoxypentyl)-1-alkyne substituted cyclopentanols by FeCl3-promoted one-pot protocol in moderate yield and high diastereoselectivity. The relative configuration was determined by X-ray experiment. And plausibe mechanisms were proposed at the basis of experiments.