Diversity-oriented synthesis and cytotoxic screening of fused dihydropyrazin-2(1H)-ones through a Ugi 4-CR/deprotection/Heck sequence

Annulation of the Ugi Products Using Palladium Catalysts

“…The purified pyrazinones 106 were then screened for cytotoxicity in various cancer cell lines. Two derivatives indicated the best inhibition and IC 50 values of 23.6 and 20.9 μM against the prostate cancer cell line PC‐3, in comparison with the nannozinone B and etoposide as standard compounds, showing IC 50 values of 16.9 and 8.3 μM, respectively [64] …”

One‐pot synthesis of novel spirocyclic‐dihydropyrazine‐2‐(1H)ones through a Ugi 4‐CR/deprotection

“…However, the IMCRs result in the formation of linear products since no spontaneous cyclization is observed upon the formation of Ugi products. Therefore, postcondensation transformations are needed in order to obtain the cyclic analogs since they are highly desirable for potentially improved structural and biological properties [7][8][9][10]. Piperazine rings are important structural heterocycles in pharmacologically active compounds [11].…”

“…Several methodologies have been reported for the preparation of heterocyclic compounds containing the dihydropyrazin-2(1H)-one motif using the tandem Ugi/post-Ugi reactions (Scheme 1a-e) [7,8,16,26,27]. Inspired by the impressive activities of oxopiperazines as well as spirocyclic-piperazines [28,29] and in continuation of our investigation in searching for new piperazine derivatives [30][31][32][33], we report a sequential one-pot Ugi/post-Ugi intramolecular annulation approach for the synthesis of novel spirocyclic-dihydropyrazine-2-(1H)ones (Scheme 1f).…”

Four-Component Synthesis of Polysubstituted Pyrazin-2(1H)-ones through a Ugi/Staudinger/Aza-Wittig/Isomerization Sequence

“…The pyrazinone skelecton also exists in some natural products such as peptide JBIR-56 isolated from marine streptomyces, sorazinone B from myxobacteria, and marinopyrazinones A or B isolated from Gram-negative bacteria (Figure ). Due to the significant bioactive properties of the pyrazinone moiety, many efforts have been devoted to the preparation of their derivatives (Figure S1, Supporting Information). − For examples, some pyrazin-2­(1 H )-one derivatives were conveniently obtained by cyclization of α-amino nitriles with oxalyl chloride . Gold-catalyzed intramolecular nucleaphilic addition of N -propargyl peptides produced 3,4-dihydropyrazin-2­(1 H )-ones in good to excellent purities under solid-phase conditions .…”

“…Ring transformations of the mesoionic 1,3-oxazolium-5-olates with TosMIC were used to prepare some pyrazin-2­(1 H )-one derivatives in moderate yields . Other pyrazin-2­(1 H )-ones were also assembled by multicomponent Ugi/deprotect/cyclize (UDC) strategy or Ugi/deprotection/Heck sequence. , Despite the above achievements, most of these methods require several steps and strongly acidic conditions, or the use of precious and hazardous transition metal catalysts. Therefore, the development of new efficient methods for the synthesis of multisubstituted pyrazin-2­(1 H )-ones under mild reaction conditions is in high demand in the discovery of biologically active compounds.…”