One pot synthesis of selenocysteine containing peptoid libraries by Ugi multicomponent reactions in water

Abstract

Selenocysteine containing peptoids and peptide-peptoid conjugates were synthesized by combinatorial Ugi-MCRs (multicomponent reactions) in water: for the first time, an acetal (selenoacetal 2a) was used in Ugi-MCR to furnish selenocysteine peptoids in one step as model compounds for selenocysteine peptides and proteins.

Novel peptidomimetic compounds containing redox active chalcogens and quinones as potential anticancer agents

“…As before, the IMCR-based approach turned out to be rather successful for the synthesis of a range of chemically diverse sulfur-, selenium-and tellurium-containing peptidomimetic compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). These compounds were tested in various cancer cell lines and, in the case of the tellurium compounds, showed considerable activity in many of these cell cultures, possibly by selectively damaging the ER and actin cytoskeleton, delaying the cell cycle and inducing apoptosis.…”

“…As far as the chemical synthesis is concerned, readily available building blocks, including isonitriles were used in the Passerini and Ugi MCRs for the synthesis of 18 peptidomimetic compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) (Figure 2). The individual building blocks used are shown in Figure 1, whereby the isonitriles were prepared in a good yield (up to 82 %) by dehydration of their corresponding formamides using phosphoryl chloride (POCl 3 ).…”

“…In fact, among the various MCRs, the Ugi and Passerini reactions can be considered a breakthrough as far as diversity of products, chemo-, regio-and stereoselectivity and ease of operation are concerned. [4][5][6][7] At the same time, chalcogen containing peptoids often also exhibit pronounced -yet also selective -biological activities [8][9][10] , especially in the context of redox-modulation. Although, several preparative methods are nowadays available for the preparation of simple chalcogen-containing molecules, there have been only a few reports on the synthesis of more sophisticated compounds, such as larger, multifunctional selenium-or tellurium compounds or biologically 'more amenable' structures, such as redox-active seleno-and telluropeptoids.…”

Synthesis of Selenocysteine and Selenomethionine Derivatives from Sulfur‐Containing Amino Acids

“…In this case, the SeCys derivatives were obtained as racemic mixtures. As the miscellaneous synthesis (Route 2E), Wessjohann [52] recently reported an application of Ugi reaction to one-pot combinatorial synthesis of various SeCys peptoids (Scheme 6).…”

Synthesis and Medicinal Chemistry of Muraymycins, Nucleoside Antibiotics

“…37,38) In our study, 2,4-dimethoxybenzylamine was chosen as a "masked" ammonia, and the resulting 2,4-dimethoxybenzyl (DMB) group at the tertiary amide site after the U4CR can be removed by acidcatalyzed hydrolysis. [39][40][41] Compounds 17, 30, isovaleraldehyde, and 2,4-dimethoxybenzylamine were mixed without any solvent 42) at room temperature for 72 h provided the desired Ugi products 31 in 54% yield as a mixture of diastereomers (1 : 1) at the α-position of the Leu residue. The final deprotection of 31 successfully afforded (−)-MRY D2 (1) and epi-MRY D2 (32) after HPLC separation of the diastereomers and we have accomplished the first total synthesis of 1.…”