CATRATS · Catalytic Enantioselective Allene Cycloisomerisation Reactions for Alkaloid Total Synthesis
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2017-06-12 → 2019-06-11
- Финансиране от ЕС
- 183 455 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Нови химични катализатори се използват за създаване на сложни молекули, като например предшественици на алкалоидите леуконицин А и В. Тези структури са основа на много природни съединения с биологични свойства, които могат да бъдат полезни за обществото.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Catalytic Enantioselective Allene Cycloisomerisation Reactions for Alkaloid Total Synthesis
The morphan core is common to >300 natural products, some of which have very important biological properties that may benefit society. Synthetic access to such compounds is challenged by the fact that the morphan is inherently chiral and enantioseletive methods are needed. Catalysing such reactions requires the development of novel catalysts and catalytic systems. The aim of this project was to discover a new catalysed reaction that could access these desirable motifs from easily synthesised allene-linked substrates, and to explore the scope of the reaction with respect to all possible variations. During the course of this project, we have developed a desymmetric intramolecular cyclization of N/O-tethered allenyl cyclohexanones by means of a dual catalytic system via concomitant activation of the cyclohexanone with chiral prolineamide and activation of the allene with copper catalyst is reported. This cyclization strategy provides a reliable solution to construct 4-vinyl-2-azabicyclo[3.3.1]nonan-6-ones, the key precursors of leuconicine A and B. In addition, this cyclization strategy has been successfully expanded to the construction of 4-vinyl-2-oxabicyclo[3.3.1]nonan-6-ones with excellent diastereoselectivity and enantioselectivity. Additionally, we discovered a new enantioselective insertion of diazo compounds into C-C bond of 1.3-dicarbonyl compounds. This reaction provides an efficient method for the construction of an all-carbon quaternary stereocenters, which could be of great interest. There is no sufficient time for me to finish this reaction, and the further research about this transformation is ongoing in our lab.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
A new catalytic enantioselective cycloisomerisation reaction for the direct creation of the azabicyclic core of strychnos alkaloids is proposed. Strychnos alkaloids have been the subject of intensive investigation over the last decades. Recently, leuconicines A and B, which are new members of the Strychnos alkaloid family, have been isolated from extracts of the Malaysian plant Leuconotis maingayi. Leuconicines possess significant bioactivity and they potently reverse multidrug resistance in vincristine-resistant leukemia cells. However, further studies into the biological profile of these natural products are hindered due to insufficient quantities being available from the natural source. In order to secure sufficient quantities and fully determine the therapeutic potential of the leuconicines, a new source of these target molecules is required. A new synthetic route which develops and incorporates ‘state-of-the-art’ methodologies to rapidly forge the extremely complex 6,5,5,6,6,6 hexacyclic ring system and 4 stereocenters, will provide the material. Nevertheless, the synthetic routes toward complex natural products are usually long, contain many individual steps and involve manipulations after each step. For these reasons, new, simple and synthetically efficient organic transformations which reduce the drain of resources are desired. This Fellowship project combines total synthesis, new catalytic enantioselective methodology development, computational calculations and biological evaluation. It has been designed to augment and complement the research and transferable skills sets of the Marie Curie fellow and will greatly enhance his career prospects accordingly. Through the training and the research results arising, the Fellowship will be beneficial to the fellow, the host institution and European science.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз