This article describes the design and optimization of an effective microwave-assisted multicomponent reaction to produce a novel class of phosphopeptidomimetic compounds. When using aminophosphonic acids (α, β, γ), aldehydes, and isocyanides as reactants and alcohols as solvents, these building blocks are merged to functionalized amido-aminophosphonate structures in a novel Ugi-type one-pot transformation reaction. A high level of structural diversity can be achieved with this synthetic approach, providing a platform for the production of functionalized building blocks for novel bioactive molecules. The general scope of this multicomponent synthetic protocol is explored by variation of reaction parameters together with an evaluation of a diverse set of reaction substrates. The applicability of this reaction has been demonstrated by the synthesis of 17 distinct compounds giving yields in the range of 20-92%.