Development of new linkers for the formation of aliphatic C-H bonds on polymeric supports
Two polymeric linkers, 8 and 11, were prepared in high yields. Attachment of an alkyl group to these linkers was facile, and their cleavage from the MeO-PEG polymer support was accomplished by desulfurization using Raney nickel to yield the new carbon-hydrogen bond product 6. The protocol reported herein allows efficient preparation of new polymeric linkers as well as their possible application to combinatorial libraries.
A linker that allows efficient formation of aliphatic C-H bonds on polymeric supports
Alkyl group bearing polymer 10 was prepared by way of sulfide 8 and thiol 11 in high yields. Cleavage of the alkyl chain from the PEG polymer support was accomplished either by homolysis under radical conditions or by desulfurization using Raney nickel to yield the new carbon-hydrogen bond product 12. The methodology developed will allow a variety of molecular scaffolds to be readily manipulated on a polymeric matrix.
Rapid assembly and in situ screening of bidentate inhibitors of protein tyrosine phosphatases
We have successfully designed and synthesized a small library of protein tyrosine phosphatase (PTP) inhibitors, in which the so-called "click chemistry" or Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction was carried out for rapid assembly of 66 different bidentate compounds. Subsequent in situ enzymatic screening revealed a potential PTP1B inhibitor (IC50 = 4.7 μM) which is 10-100 fold more potent than other PTPs.