Preparation of arylphosphinic acid derivatives as building blocks for binding sites

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1992
Authors
Grady, Haiyan
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Abstract

Several members of a new class of potential binding sites have been designed and prepared from a novel bis amino acid, bisphenylalanylphosphinic acid. The synthesis starts by making 4-iodophenylalanine, for which a greatly improved preparation has been developed. With this method, multi-gram quantities of 4-iodo-(S)-phenylalanine can be obtained easily in one step without racemization. The synthesis of bisphenylalanyl phosphinates, building blocks for binding sites, is an important part in the binding site synthesis. A simple and effective preparation of methyl ester of monoarylphosphinic acids has been developed, which involves palladium catalyzed coupling of aryl iodides with methyl phosphinate. This procedure is compatible with various functional groups and proceeds in reasonable yields. Symmetrically substituted diarylphosphinates can be prepared using two equivalents of the aryl iodide. Unsymmetrically substituted diarylphosphinates are readily obtained from the monoarylphosphinates derived from methyl phosphinate. Deprotection of the bisphenylalanylphosphinate and mixing it with a metal ion lead to self-assembled cyclic metal complex of bisphenylalanyl phosphinic acid. Selective deprotection and peptide coupling of bisphenylalanylphosphinate generate a dipeptide or a macrocyclic peptide. This macrocycle has a non-polar cavity, a hydrophilic external surface and multiple functional groups. The new method for making arylphosphinates also provides a general pathway for synthesis of inhibitors of tyrosine phosphatase;In connection with this research on molecular recognition, we developed an assay for rapidly screening many molecules for binding to a specific ligand. This assay is a novel application of two-dimensional thin layer chromatography.

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Chemistry, Organic chemistry
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