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Lecture

Chemical Biology Lecture: Multicomponent Syntheses of Heterocycles

Date
Thursday 4 October 2018
Time
Location
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden
Room
GM4.13

We are delighted to kick off the new season of the Chemical Biology Lecture series with the lecture of Prof. Romano Orru from the department of Chemistry and Pharmaceutical Sciences at the VU Amsterdam. Prof Orru works on the development and application of novel chemical reactions to the synthesis of heterocycles. In recent years he has been making waves with the use of multicomponent syntheses to achieve this. In the application of these reactions to synthesize single products from more than three components, he shows beautiful mastery over these complex cascade reactions.

Abstract

The main research interest of my group focuses on sustainable (atom and step economic) synthetic method development employing domino (or tandem) processes. A powerful strategy involves the use of multicomponent reactions (MCRs), which are one-pot processes that combine at least three different simple reagents in a well-defined manner to form a single product. Typical MCRs proceed with high atom economy and low E factors thus minimizing the number of functional group manipulations towards a given complex molecular target and avoiding the use of protective groups.

Rapid generation of diverse sets of complex N-containing heterocyclic molecules can be achieved by employing diversity-oriented synthetic strategies in combination with so-called complexity-generating reactions. Multicomponent reactions provide a most powerful platform to access diversity as well as complexity in a limited number of reaction steps. In the presentation I will discuss novel modular reaction sequences based on our previously reported MCR chemistry in combination with other common organic reactions, biocatalysis and additional MCRs. Examples in which the synthetic methodology was applied for the easy generation of focused libraries of medicinally relevant N-heterocycles and Natural product analogs will be the focus.

References

  1. Collet, J.W.; Ackermans, K.; Lambregts, J.; Maes, B.U.W.; Orru, R.V.A.; Ruijter, E. “Modular Three-Component Synthesis of 4-Aminoquinolines via an Imidoylative Sonogashira/Cyclization Cascade” J. Org. Chem. 2018, 83, 854-861.
  2. Saya, J.M.; Oppelaar, B.; Cioc, R.C., van der Heijden, G.; Vandevelde, C.M.L.; Orru, R.V.A.; Ruijter, E. “Synthesis of polycyclic spiroindolines by highly diastereoselective interrupted Ugi cascade reactions of 3-(2-isocyanoethyl)indoles”, Chem. Commun. 2016, 52, 12482-12485.
  3. de Graaff, C.; Oppelaar, B.; Péruch, O.; VandeVelde, C.M.L.; Bechi, B.; Turner, N.J.; Ruijter, E.; Orru, R.V.A. “Stereoselective Monoamine Oxidase-Catalyzed Oxidative Aza-Friedel–Crafts Reactions of meso-Pyrrolidines in Aqueous Buffer”, Adv. Synth. Catal. 2016, 358, 1555-1560.
  4. van der Heijden, G.; Jong, J.A.W.; Ruijter, E.; Orru R.V.A. “2-Bromo-6-isocyanopyridine as a Universal Convertible Isocyanide for Multicomponent Chemistry” Org. Lett. 2016, 18, 984-987.
  5. Cioc, R.C.; Ruijter, E.; Orru, R.V.A. “Multicomponent Reactions: Advanced Tools for Sustainable Organic Synthesis” Green Chem. 2014, 16, 2958-2975.
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