Proline-like β-turn mimics accessed via Ugi reaction involving monoprotected hydrazines

Abstract

A four-center, three-component Ugi-type reaction of a variety of keto acids, Boc-or Cbz-protected hydrazine, and isocyanides offers a simple and high-yielding access to cyclic products containing an N-aminolactam unit. The latter are shown to form consistently an intramolecular hydrogen bond leading to a -turn-like secondary structure. The possibility of integrating such N-aminolactam units (without disruption of the folded structure) into pseudotripeptide fragments is demonstrated.The successful use of keto (as well as aldehydo) carboxylic acids as bifunctional inputs for isocyanide-based multicomponent reactions (IMCR) was demonstrated by Harrimann 1 and Ugi. 2 This four-center, three-component process was found to provide a simple and efficient (as well as atom-economical) entry into novel dipeptoid lactam structures. The strategy has been aggressively exploited to give rise to a wide variety of novel small-and medium-size lactamtype heterocyclic scaffolds 3 and validated, in general, the use of bifunctional reagents in IMCR as a source of significant product diversity. 4

Anionic and neutral 2D indium metal–organic frameworks as catalysts for the Ugi one-pot multicomponent reaction

“…27,28 In particular, we have evaluated the Ugi organic transformation, 33,34 which involves the condensation among four substrates, in this case a carbonylderivate, an amine, a carboxylic acid, and an isocyanide to form α-aminoacyl amide derivatives, which are important in the pharmaceutical industry and fine chemistry to develop organic drug-like molecule libraries. [35][36][37] Out of the evaluated MOFs we found that those with a suitable ratio of acid and basic sites in their structure displayed the best catalytic performance. 27 Both, InPF-50, and -51, are formed by SBUs composed of only one metal cation, with accessible acid sites.…”

Synchronizing Substrate Activation Rates in Multicomponent Reactions with Metal–Organic Framework Catalysts

“…[19] The Ugi four-component reaction( U-4CR) is perhaps oneo f the most important isocyanide-based MCRs. [19][20] It is avaluable methodf or generating a-aminoacyl amide derivatives in av ery straightforward manner by the condensation of an aldehyde, amine, carboxylic acid, and isocyanide in ao ne-pot reaction. [18] Lewis acids are not alwaysr equired for many of the reported isocyanide-based MCRs;h owever,t oo btain good yields and selectivity in the U-4CR,L ewis acid catalysts do have to be used.…”

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

“…There are several reports on the use of hydrazones in Ugi reactions [14–23], however, to the best of our knowledge, there is no report involving α-hydrazonocarboxylic acids.…”