Towards the ideal synthesis: Development of a sequence of cascade reactions and its application in the synthesis of a natural compound by researchers at the Research Centre for Natural Sciences


The research staff of the Research Centre of Natural Sciences have developed an efficient method based on a sequence of cascade reactions that enables the production of several natural compounds. This has attracted the attention of the scientific community.

The synthesis of complex natural compounds has a rich history and is still a key area of research in chemistry. A series of milestone discoveries and revolutionary innovations in the logic of synthesis design offers an exceptional opportunity for today’s practicing chemists: with enough time and resources, they can produce molecules of almost any complexity. Thanks to the current state of development in the 21st century, it is no longer the capability for synthesis that is important but its efficiency, i.e. the need is for an organic compound to be produced using the simplest possible method, within the shortest time and requiring the least effort and expense. The expectation of modern syntheses is for an integrated approach and encourages further innovation. As so many times before, nature provides an inspiring example to researchers looking for solutions. Particular emphasis is given to mimicking the ability of enzymes to facilitate several chemical steps, i.e. cascade reactions, in a coordinated and selective manner. By using cascade reactions, the synthetic route can be significantly shortened, while time-consuming and costly isolation steps can be eliminated.


One of the most important families of natural compounds for medicine is that of terpene-indole alkaloids, many of which are used in the treatment of cancer, malaria and diseases of the central nervous system. In the course of their work, researchers at the Research Centre for Natural Sciences have developed processes for the production of biologically important and chemically challenging aspidospermane-based terpene-indole alkaloids. The complex structure of the compounds was created by a sequence of high-efficiency cascade reactions, and the central building block of the syntheses was also produced by a scaled process in batches of 100 grams. This efficient and modular route to synthesis also provides an opportunity to produce derivatives, this significantly expanding the chemical scope for drug development. Thanks to the structural features of the central building element, so-called divergent synthesis also becomes possible, i.e. several natural compounds can be created from the common building block.

The research staff of the Research Centre for Natural Sciences– Szilárd Varga, Péter Angyal, Gábor Martin, Orsolya Egyed, Tamás Holczbauer and Tibor Soós (head of the Frustrated Lewis Pairs “Lendület” Group) – have published a report to the scientific community on a procedure that can be used to synthesise five natural compounds by means of the shortest, most efficient and selective series of transformations known so far. Of these, the gram-scale production of (-) - minovincine, an important point of departure for organic synthesis, and the synthesis of cage-structured, highly complex (-) - aspidofractinine have been reported in Angewandte Chemie, a leading journal in the field of chemistry [1]. The significance of the results achieved is shown by the fact that Synfacts, a monthly magazine publishing the most important results of organic chemistry, also highlighted their achievements[2].

Building on this strategy, the synthesis of three additional alkaloids has also been accomplished, which has been disclosed in Organic Letters, the leading journal of organic chemistry, and in Nature Index [3] [4]. Nothing shows the interest of the scientific community in their achievements better than the fact that it was the most read publication in the journal in June, with more than 2,500 views [5].

Under the National Electronic Information Service Program, both publications have been made available to anyone free of charge. [6]