A Synthesis of Spirooxindole‐Isoindolinones Through Ugi Reaction Followed by Copper‐Catalyzed Tandem C−N/C−C Coupling Process

Zhong, Xianqiang; Luo, Jianghao; Zhou, Wei; Cai, Qian

doi:10.1002/adsc.202100889

Cited by 10 publications

(5 citation statements)

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“…In 2021, Cai and co‐workers presented a copper‐catalyzed cascade C−N/C−C coupling process of Ugi adducts for the construction of spiroindolinone‐isoindolinone skeletons in moderate to good yields (Scheme 28). [29] Substituents on the 2‐iodobenzic acid with an electron‐donating group such as methyl and methoxy, or an electron‐withdrawing group such as fluoro, chloro and bromo, worked well, delivering the products in moderate to good yields. Substituted 2‐iodobenzaldehydes carrying an electron‐donating group or an electron‐withdrawing group were well tolerated, yielding the products in moderate to good yields.…”

Section: Polycyclic Peptidomimeticsmentioning

confidence: 99%

Recent Advances in the Synthesis of Peptidomimetics via Ugi Reactions

Liu,

Voskressensky,

Van der Eycken

2024

Chemistry A European J

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Peptidomimetics have been extensively explored in many area due to their ability to improve pharmacological qualities and interesting biological activities. Cycles could be incorporated in peptides to reduce their flexibility, often enhancing the affinity for a certain receptor. Many efforts have been made to synthesize various peptidomimetics. Among them, the Ugi reaction is a popular way for the synthesis of peptidomimetics because it provides peptide‐like products. The Ugi reaction consists of the condensation of an aldehyde or ketone, a carboxylic acid, an amine, and an isocyanide usually giving a linear peptidomimetic. In order to obtain other linear, cyclic or polycyclic peptidomimetics, the acyclic products have to undergo additional transformations or cyclizations. This review covers the years from 2018‐2023, regarding the synthesis of linear, cyclic and polycyclic peptidomimetics, employing Ugi reactions eventually followed by post‐Ugi transformations. Organo‐catalyzed reactions, base‐promoted reactions, and metal‐free reactions toward peptidomimetics are highlighted.

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Section: Polycyclic Peptidomimeticsmentioning

confidence: 99%

Recent Advances in the Synthesis of Peptidomimetics via Ugi Reactions

Liu,

Voskressensky,

Van der Eycken

2024

Chemistry A European J

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“…Screening of conditions enabled selective synthesis of spirooxindole–isooxindole 8 a [9c] and spirooxindole–oxindole 9 a from N ‐pivaloyloxy benzamide 1 a and different diazooxindoles 5 a and 7 a , respectively (Table S1). N ‐benzyl diazooxindole 5 a as the substrate yielded the annulation product 8 a (91 % yield, isomer ratio 8 a : S7 >20 : 1) in THF, whereas in acetonitrile in the presence of the electron‐withdrawing methanesulfonamide ( 7 a ), a Lossen‐rearrangement led to highly selective formation of 9 a in high yield (82 % yield, isomer ratio S10 : 9 a <1 : 20, see Scheme 1, for a detailed discussion see Table S1).…”

Section: Figurementioning

confidence: 99%

Morphological Profiling Identifies the Motor Protein Eg5 as Cellular Target of Spirooxindoles

et al. 2023

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Oxindoles and iso‐oxindoles are natural product‐derived scaffolds that provide inspiration for the design and synthesis of novel biologically relevant compound classes. Notably, the spirocyclic connection of oxindoles with iso‐oxindoles has not been explored by nature but promises to provide structurally related compounds endowed with novel bioactivity. Therefore, methods for their efficient synthesis and the conclusive discovery of their cellular targets are highly desirable. We describe a selective RhIII‐catalyzed scaffold‐divergent synthesis of spirooxindole–isooxindoles and spirooxindole–oxindoles from differently protected diazooxindoles and N‐pivaloyloxy aryl amides which includes a functional group‐controlled Lossen rearrangement as key step. Unbiased morphological profiling of a corresponding compound collection in the Cell Painting assay efficiently identified the mitotic kinesin Eg5 as the cellular target of the spirooxindoles, defining a unique Eg5 inhibitor chemotype.

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“…2-Iodobenzaldehyde, 2-iodobenzoic acid, methylamine and tert -butyl isocyanide were selected to be model substrates. The reaction proceeds via C–N coupling, which facilitates N -arylation followed by C–C coupling, furnishing spiro derivatives 108 (Scheme 89).…”

Section: Tandem Copper-catalyzed N-arylation–c/n/o/s–arylationmentioning

confidence: 99%