Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids.

The synthesis of six cyclic depsipeptoids inspired by the natural depsipeptide sansalvamide A is described. An efficient and fast synthetic strategy was developed using a combination of consecutive isocyanide-based multicomponent reactions (Ugi and Passerini reactions). This methodology can be used to access a variety of cyclic oligodepsipeptoids.

Fast and efficient microwave-assisted synthesis of functionalized peptoids via Ugi reactions.

A wide range of N-alkylglycines (peptoids) can be efficiently prepared via Ugi reactions using microwave irradiations. The results confirm the versatility and efficiency of the methodology for the preparation of functionalized peptoids. The products can be used in consecutive Ugi reactions to yield cyclic peptoids of potential biological interest.

Rapid generation of macrocycles with natural-product-like side chains by multiple multicomponent macrocyclizations (MiBs).

A small parallel library of peptoid macrocycles with natural-product-derived side chains of biological importance was produced by Ugi-type multiple multicomponent macrocyclizations including bifunctional building blocks (Ugi-MiBs). Diverse exocyclic elements of high relevance in natural recognition processes, i.e., all functional amino acid residues (e.g., Cys, Arg, His, Trp) and even sugar moieties, can be introduced in a one-pot process into different types of peptoid-containing macrocyclic skeletons. This is exemplified by the use of a diamine/diisocyanide combination of Ugi-MiBs and N-protected alpha-amino acids or carboxy-functionalized carbohydrates as source for the natural-product-like exocyclic elements. Employed as the acid components of the multiple Ugi reactions, they appear as N-amide substituents on the macrocyclic cores. The use of different diamines and diisocyanides allows an easy variation of the N- to C-directionality and therefore of the position of the exocyclic elements.

Design and synthesis of cyclic RGD pentapeptoids by consecutive Ugi reactions.

A new strategy for the synthesis of cyclic peptoids was developed. The approach is based on the use of consecutive Ugi reactions for the assembly of the acyclic peptoid and for the ring closure. Cyclopentapeptoid analogues of the RGD peptides were designed and synthesized using this methodology. The results confirm the versatility and efficiency of the method for the preparation of cyclic oligopeptoids.