6533b7d9fe1ef96bd126c2a0
RESEARCH PRODUCT
A three-component Mannich-type condensation leading to phosphinic dipeptides—extended transition state analogue inhibitors of aminopeptidases
Arthur MuchaMałgorzata PawełczakAnna Dziełaksubject
chemistry.chemical_classificationDipeptideStereochemistryCarboxylic acidOrganic ChemistryPeptidePhosphorus acidCondensation reactionBiochemistryAmino acidchemistry.chemical_compoundtransition state inhibitorschemistryTransition state analogDrug DiscoveryphosphinomethylationaminopeptidasesMannich reactionMannich condensationdescription
Abstract N-Protected α-aminoalkylphosphinic acids bearing a P–H function were found to be novel practical building blocks in three-component condensations with formaldehyde and secondary amines (amino acids). Such Mannich-type N -phosphonomethylation is a common approach for phosphorus acid derived substrates and leads to multifunctional (phosphonic/amino/carboxylic) compounds of diverse relevance. The utility of this reaction was examined for construction, in a single synthetic step, of advanced phosphinic pseudodipeptides designed to act as extended transition state analogue inhibitors of selected aminopeptidases. Phosphinomethylation of primary amino acids was less efficient and yielded mixtures of products which were separated into individual components, and their structures identified.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-06-01 | Tetrahedron Letters |