German scientists have developed a solid-phase approach to the synthesis of a class of natural product, Jasplakinolide, analogs via "click" chemistry. 

Natural products are a group of molecules that nature itself has evolved to bind to proteins. A lot of natural products are found to possess biological activity for use in pharmaceutical drug discovery and drug design. The natural product jasplakinolide is a 19-membered macrocylic compound isolated from marine Jaspis sponges and is known to possess a remarkable anti-cancer activity profile. 

A team led by Herbert Waldmann has developed an efficient and easy approach to the synthesis of jasplakinolide analogs which contain a 1,2,3-triazolyl component, some peptide-motifs and some non-peptidic structures. For the synthesis of the precursors, the team employed a combination of solution-phase and solid-phase methods. Two types of macrocyclisation methods were then compared: a classical macrolactamisation approach and an alternative one that features a copper (I) catalysed azide-alkyne cycloaddition reaction also known as the "click" reaction. Remarkably, Waldmann found that the "click" chemistry is generally higher yielding than the traditional macrolactamisation. 

'A methodology as the one developed will provide access to numerous analogs of the guiding natural product and maybe deliver new molecules that influence cell division and stability which certainly is of interest from the point of view of drug development,' says Waldmann. 

There are many challenges facing future research in this area. 'It is like finding a needle in the haystack,' commented Waldmann. 'Instead of increasing the size of the haystack, you want to find a magnetic viewing glass! That is what we are trying to do'. 

Kathleen Too