Click chemistry in automated synthsis of 96-product library with solid-supported catalyst

First published on April 28, 2010

Girard et al, Molecules, doi:10.3390/molecules15053087

After a 2006 report (Org. Lett. 8, 1689) on a solid phase supported Copper (1+) catalyst for alkyne-azide click reaction ), this article showcases the use of the catalyst system in an automated synthesis of a 96 product-sized triazole library.

Several interesting things. First, they use the automated chemical synthesis station for high-throughput (ChemSpeed ASW-2000). Second, HNMR monitoring of the click reaction was an elegant kinetics measurement. Third, the stability and recycled use of the catalyst are impressive – 5 cycles over 5 days!

At least two questions can be asked. First, Cu(1+) leaching may still be a problem in certain applications / systems / solvents. Second, the resin swelling was not considered in the solvent effect for the click reaction.
An ideal solid-supported catalyst needs have the following: Cu(1+) should be chelated in a kinetically / thermodynamically stable complex for zero leaching yet highly reactive in catalysis; the immobilization should allow reaction components to access the catalyst easily; the resin should be insensitive to solvent choice, preferably including water.
A long way to go!
                          

Click chemistry reagents offerings from Novabiochem / EMD

Novabiochem Letters 2010, No. 1/10

The peptide giant, Novabiochem Brand from EMD, opened its click chemistry reagents offerings in peptide synthesis proucts lines. Newly availabe are a range of suitably protected amino acids bearing azide or terminal alkyne functionalities, in addition to some intermediates bearing these functional groups. They are designed for click chemistry ligations which possess the following features and benefits:
*High yielding ligation in aqueous media
*Orthogonal to standard methods of ligation
*Building blocks compatible with standard Fmoc SPPS methods

Notably, one caution was given that thiols lead to azide reduction.

Previously a list of click reagents vendors was given -
http://clickchemistry.blogspot.com/2010/02/click-chemistry-reagent-vendors-matter.html

This list is expected to grow - and that is only good news to our click chemistry users!