Gydo van der Heijden
Gydo van der HeijdenPhD Student
 11/2012 – present
Room:  O|2-4W33
Lab:  O|2-4W35
Phone:  +31 (0)20 59 87488

Biocatalysis and Multicomponent Reactions:

The ideal combination for green chemistry

The multistep total syntheses of complex drugs are often lengthy with many reaction steps and employ a multitude of different, sometimes highly reactive, reagents, catalysts, and protecting group strategies. As a result, the production processes in the pharmaceutical industry are very wasteful and cost inefficient. As part of the “Chem21: Chemical Manufacturing Methods for the 21st Century Pharmaceutical Industries” project initiated by the European Union through the Innovative Medicines Initiative”[1] we are involved in tackling this problem by the development of short and efficient synthetic routes towards existing drugs.

Multicomponent reactions (MCRs) have proven to be excellent candidates for the short and efficient synthesis of complex targets since they approach the ideal synthesis (Figure 1). In these reactions often multiple covalent bonds and several stereocenters are formed in a single reaction step with a high tolerance of different functional groups. Consequently, the use of protection groups can be avoided, which reduces the amount of reaction steps significantly. However, a major challenge in MCR chemistry is the overall poor stereocontrol in most of these reactions.

GA1 Gydo
Figure 1: Ideal Synthesis

Biocatalysts offer a broad repertoire of stereospecific conversions for the synthesis of functionalized building blocks to address the selectivity issues of MCRs. In addition, biocatalitical processes often require just one reaction step to provide products with high purity without the need of tedious protecting and deprotecting steps. The combination of biocatalytic principles with MCR strategies would represent a highly desirable approach towards the green synthesis of bioactive compounds (Figure 2). This concept has been convincingly validated by the elegant synthesis of the hepatitis C drug Telaprevir.[2]

GA2 Gydo
Figure 2: Combination of biocatalysis and MCRs.

My PhD involves the development of more efficient synthetic route towards complex bioactive compounds, utilizing the excellent synergy between MCRs and biocatalysis.

[2] A. Znabet et al., Chem. Comm., 2010, 46, 7918.


van der Heijden, G.; Ruijter, E.; Orru, R. V. A. Synlett 2013, 24, 666–685.