A Manifold Three‐Step Synthetic Route to Polycyclic Annulated Hydantoins <i>via</i> Cyclic Imines

Brockmeyer, Fabian; Kröger, Denis; Stalling, Timo; Ullrich, Pasqual; Martens, Jürgen

doi:10.1002/hlca.201200441

Cited by 14 publications

(4 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(Scheme 37). 126 In another interesting work, they developed a novel strategy for easy access to tricyclic heterocycles 121 through a high diastereoselective Cumediated rearrangement reaction based on the bis-amides 118 (Scheme 37). 127 In 2016, they designed an efficient synthetic route for constructing thiazolo-and oxazoloannulated benzodiazepinediones 122 by employing the compounds 119 that allow final single-step cyclization via the S N Ar process (Scheme 37).…”

Section: ■ Introductionmentioning

confidence: 99%

Cyclic Imines in Ugi and Ugi-Type Reactions

et al. 2020

View full text Add to dashboard Cite

Ugi four-component reactions (U-4CRs) are widely recognized as being highly efficient for the synthesis of pseudopeptides. However, the products of these reactions are not so interesting as drug candidates because they are not conformationally restricted enough for a potent interaction with biological targets. One possible way to overcome this problem is to replace amine and oxo components in the U-4CRs with cyclic imines in so-called Joullié−Ugi three-component reactions (JU-3CRs). This approach provides a robust single-step route to peptide moieties connected to N-heterocyclic motifs that are found as core skeletons in many natural products and pharmaceutical compounds. JU-3CRs also provide much better diastereoselectivity than their four-component analogues. We survey here the redesign of many synthetic routes for the efficient preparation of a wide variety of three-, five-, six-, and seven-membered heterocyclic compounds connected to the peptide backbone. Additionally, in the Ugi reactions based on the cyclic imines, α-acidic isocyanides, or azides can be replaced with normal isocyanides or acids, respectively, leading to the synthesis of N-heterocycles attached to oxazoles or tetrazoles, which are of great pharmaceutical significance. This Review includes all research articles related to Ugi reactions based on the cyclic imines to the year 2020 and will be useful to chemists in designing novel synthetic routes for the synthesis of individual and combinatorial libraries of natural products and drug-like compounds.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Cyclic Imines in Ugi and Ugi-Type Reactions

et al. 2020

View full text Add to dashboard Cite

show abstract

“…During the last decades, the effect of the structural modification on the biological activity of the hydantoin derivatives has been studied intensively [ 12 ]. Due to their various biological activities polycyclic hydantoins, especially spirohydantoins [ 13 – 20 ] and fused [ 21 – 23 ] bicyclic hydantoin derivatives, have recently attracted great interest in both organic and medicinal chemistry.…”

Section: Introductionmentioning

confidence: 99%

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

Šmit¹,

Pavlović²,

Milenković³

et al. 2015

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

The mechanism and selectivity of a bicyclic hydantoin formation by selenium-induced cyclization are investigated. The proposed mechanism involves the intermediates formed by an electrophilic addition of the selenium reagent on a double bond of the starting 5-alkenylhydantoin prior the cyclization. These intermediates are readily converted into the more stable cyclic seleniranium cations. A key step of the mechanism is an intramolecular cyclization which is realized through an anti-attack of the internal nucleophile, the amidic nitrogen, to the seleniranium cation yielding the intermediate imidazolinium cations. Their deprotonation is followed by the formation of the fused bicyclic reaction products. Important intermediates and key transition states are studied by using density functional theory (DFT) methods. The pathways of the reaction are investigated in detail. There are two regioselective pathways related to 5-exo and 6-endo products. Theoretical calculations and the monitoring of the cyclization reaction using 1 H NMR spectroscopy are in a good agreement with the proposed mechanism and are consistent with our experimental results. The preferred pathway for formation of 5-exo products is confirmed.1865

show abstract

“…Spirohydantoins and fused polycyclic hydantoins are the leading compounds in drug discovery due to their various biological activities. 54 Intramolecular aminoselenation is a convenient and useful tool for constructing these heterocycles. For example, Šmit et al described an electrochemical aminoselenation method for the synthesis of bicyclic and tricyclic fused hydantoin scaffolds (Scheme 17).…”

Section: Intramolecular Selenofunctionalizationmentioning

confidence: 99%