[2+2+2] cyclotrimerization in synthesis of selaginpulvilin A and C

• Main Author: Mateus, Miguel Alexandre Gomes
• Publication Date: 2020
• Format: Master thesis
• Language: eng
• Source: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Download full: http://hdl.handle.net/10362/129172
• topic: [2+2+2] cyclotrimerization; Natural products; Fluorene scaffold; Selaginpulvilin A; Selaginpulvilin C; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

Since pre-historic ages natural products are employed as medicine by humans. Combi natorial chemistry and high-through-put screening (HTS) process were presented, in the end of the 20th century, has revolutionary methods for the discover of new natural products and their analogues. However, this process failed in reliability, being time-consuming and expensive. Consequently, it left the necessity of finding new affordable techniques to achieve such natural products and analogues. The [2+2+2] cyclotrimerization is a simple yet elegant technique to synthesise a wide variety of functionalized cyclic frameworks. A variety of metals are now used as catalysts in the [2+2+2] cyclotrimerization. Particularly, rhodium catalyst complexes are in the spotlight of chemists, being the RhCl(PPh3)3, known as Wilkinson’s catalyst, the most used. [2+2+2] cyclotrimerization is applied in a variety of fields, including natural prod ucts, materials and miscellaneous. An important application of the [2+2+2] cyclotrimerization is the synthesis of fluorene scaffold. The fluorene scaffold in present in a variety of natural products. Selaginpulvilins are a fluorene derivative with a 6-5-6 carbocyclic system. It is an important structure to pharmaceutical industry and has been used in the Traditional Chinese Medicine for the treatment of dysmenorrhea, asthma, and traumatic injury. In this work we report the use of [2+2+2] cyclotrimerization as a key step for the syn thesis of selaginpulvilin A and C. In a first stage of the project the reliability of the technique was investigated by reacting various starting materials in order to determine the scope and limitations of the key transformation. The main objective of this investigation was the deter mination of an influence of various alkynes upon the course of the cyclotrimerization, in par ticular on the regioselectivity and reaction yields. It was possible to obtain the respective fluo rene scaffold using a variety of alkynes with yields up to 69%. After the determination of the scope of the [2+2+2] cyclotrimerization the next stage was to employ this technique in the synthesis of selaginpulvilins. It was possible achieve the formal synthesis of selaginpulvilin C. The total synthesis of selaginpulvilin A was not achieved due to difficulties in the last stages of the synthesis. The investigation for the synthesis of this natural product is still undergoing.