Professor Viktor Krchnák, University of Notre Dame, presents the following seminar at the eCombiChem “Cutting Edge Technologies in Combinatorial Chemistry” Web Conference running at http://ecombichem.com/:
Solid-Phase Synthesis on Dual Linkers with a Reference Cleavage Site
Optimization of reaction conditions is a key factor for successful solid-phase synthesis. The assessment of a chemical transformation on solid phase includes cleavage of the resin-bound reaction components followed by analysis of the cleaved sample. To obtain meaningful information regarding the composition of components on solid phase, all components need to be cleaved from the support. Information that cannot be obtained from this simple experiment is the rate of cleavage from the solid support. An independent quantification analysis is required in order to assess the cleavage yield.
We report a general, yet very simple, concept that secures cleavage of all polymer-supported components and, at the same time, estimates the cleavage rate. The synthesis is carried out on a polymer-supported dual linker with a reference cleavage site consisting of two sequential linkers separated by a spacer. The spacer is designed to allow its cleavage from the Linker 1 under standard conditions. Linkers 1 and 2 have to be cleavable with the same reagent. In a cleaved sample, the presence of the desired compound still attached to Linker 2 reveals incomplete cleavage; its absence indicates complete cleavage of compound from Linker 2.
The dual linker contributes in development of solid-phase transformations in several aspects: (i) It ensures cleavage of all resin-bound components. (ii) It allows simple estimation of the cleavage rate of polymer-supported compounds. (iii) It is suitable for straightforward optimization of cleavage protocol, including evaluation of new cleavage cocktails. (iv) It assists in selection of the most suitable linker for given compound classes. (v) It can be used for design of new linkers with altered sensitivity towards cleavage conditions.
Barry Hardy
Douglas Connect
www.douglasconnect.com
Cutting Edge Technologies in Combinatorial Chemistry: ecombichem.com
eCombiChemLeads Blog: http://barryhardy.blogs.com/ecombichemleads/
Recent Comments