This thesis is divided into three chapters. Each chapter describes a review of high-order securinega alkaloids and the total synthesis of dimeric securinega alkaloids flueggenine C, D, and I.
Chapter 1 provides a detailed review of high-order securinega alkaloids. The isolation of flueggenines A and B by Yue and coworkers in 2006 has triggered a burst of isolation reports of dimeric and oligomeric securinega alkaloid natural products. Their compelling molecular structures with various modes of connection between monomeric securinega units have posed intriguing challenges to the synthetic organic community. Herein, we have categorized high-order securinega alkaloids based on their biosynthetic mode of dimerization or oligomerization. We then have compiled all reported syntheses of dimeric securinega alkaloids based on our classification.
Chapter 2 reports the first total synthesis of dimeric securinega alkaloid (–)-flueggenine C. The total synthesis of (–)-flueggenine C is completed via an accelerated intermolecular Rauhut–Currier (RC) reaction. Despite the numerous reports on the total synthesis of monomeric securinegas, the synthesis of dimeric securinegas whose monomeric units are connected by a putative enzymatic RC reaction has not been reported to date. We have found that an installation of a nucleophilic functional group at the γ-position of an enone greatly accelerates the rate of the diastereoselective intermolecular RC reaction. This discovery enabled an efficient and selective formation of the dimeric intermediate which was further transformed to (–)-flueggenine C.
Chapter 3 reports the first total synthesis of dimeric securinega alkaloid (–)-flueggenines D and I. This features the first total synthesis of dimeric securinega alkaloids with a C(α)–C(δ’) connectivity between two monomeric units. The key dimerization was enabled by a sequence that involves Stille reaction and conjugate reduction. The high chemofidelity of the Stille reaction enabled us to assemble two structurally complex fragments that could not be connected by other methods. Stereochemical flexibility and controllability at the δ’-junction of the dimeric intermediate render our synthetic strategy broadly applicable to the synthesis of other high-order securinega alkaloids.
본 학위논문은 3장으로 이루어져 있다. 각 장은 고차원 세큐리네가 알칼로이드에 대한 고찰 및 이합체 세큐리네가 알칼로이드 플루게닌 C, D, I의 전합성에 관한 연구를 다룬다. 1장에선 세큐리네가 알칼로이드에 대한 전반적인 설명을 다룬다. 결합 방식에 따라 고차원 세큐리네가 알칼로이드들을 각각 타입 I, II, III로 분류하였고 각각의 타입에 해당하는 이합체 세큐리네가 알칼로이드의 합성 사례를 다룬다. 2장에선 향상된 라우헛.쿠리어 반응의 개발과 이를 이용한 타입III 이합체 세큐리네가 알칼로이드 플루게닌 C의 전합성에 관한 연구를 다룬다. 3장에선 스틸리 반응을 이용한 타입III 이합체 세큐리네가 알칼로이드 플루게닌 D와 플루게닌 I의 전합성에 관한 연구를 다룬다.
