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1. Unnatural Lysines with Reduced Sidechain N ‐Basicity: Synthesis of N ‐trifluoroethyl Substituted Lysine and Homologs

   https://doi.org/10.1002/slct.202203132  

   Jameson, Brian; Glaser, Rainer (December 2022, ChemistrySelect)

   Abstract The syntheses are reported of N^ϵ‐(2,2,2‐trifluoroethyl)‐D,L‐lysine (^tFK) and N^ζ‐(2,2,2‐trifluoroethyl)‐D,L‐homolysine (^tFK₊₁) from amino alcohols HO−(CH₂)_n−NH₂. The syntheses involve reductive amination, Appel bromination, and the stereoselective bond formation between C_α of the amino acid and the fluorinated alkyl chain in the Schöllkopf bislactim amino acid synthesis. The methyl esters of the fluorinated amino acids are the relevant substrates for oligopeptide synthesis. With theR‐Schöllkopf reagent, we stereoselectively generated methyl N^ϵ‐boc‐N^ϵ‐(2,2,2‐trifluoroethyl)‐L‐lysinate and methyl N^ζ‐boc‐N^ζ‐(2,2,2‐trifluoroethyl)‐L‐homolysinate. Products and intermediates were characterized by ¹H NMR, ¹³C NMR, COSY, HSQC, and LCMS. A variety of N‐functionality may be introduced by reacting hemiacetals with different appendages. This fluorine modification reduces the sidechain N‐basicity by combined ‐I effect of the three fluorines. This effect increases the [amine]/[ammonium ion] ratio of the sidechain amine in lysine to facilitate carbamylation at lower pH conditions. 

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2. ItOct (I t Octyl) – pushing the limits of ItBu: highly hindered electron-rich N-aliphatic N-heterocyclic carbenes

   https://doi.org/10.1039/D3SC01006F  

   Rahman, Md. Mahbubur; Meng, Guangrong; Bisz, Elwira; Dziuk, Błażej; Lalancette, Roger; Szostak, Roman; Szostak, Michal (April 2023, Chemical Science)

   ItBu (ItBu = 1,3-di- tert -butylimidazol-2-ylidene) represents the most important and most versatile N -alkyl N-heterocyclic carbene available in organic synthesis and catalysis. Herein, we report the synthesis, structural characterization and catalytic activity of ItOct (I t Octyl), C 2 -symmetric, higher homologues of ItBu. The new ligand class, including saturated imidazolin-2-ylidene analogues has been commercialized in collaboration with MilliporeSigma: ItOct, 929 298; SItOct, 929 492 to enable broad access of the academic and industrial researchers within the field of organic and inorganic synthesis. We demonstrate that replacement of the t -Bu side chain with t -Oct results in the highest steric volume of N -alkyl N-heterocyclic carbenes reported to date, while retaining the electronic properties inherent to N-aliphatic ligands, such as extremely strong σ-donation crucial to the reactivity of N -alkyl N-heterocyclic carbenes. An efficient large-scale synthesis of imidazolium ItOct and imidazolinium SItOct carbene precursors is presented. Coordination chemistry to Au( i ), Cu( i ), Ag( i ) and Pd( ii ) as well as beneficial effects on catalysis using Au( i ), Cu( i ), Ag( i ) and Pd( ii ) complexes are described. Considering the tremendous importance of ItBu in catalysis, synthesis and metal stabilization, we anticipate that the new class of ItOct ligands will find wide application in pushing the boundaries of new and existing approaches in organic and inorganic synthesis. 

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3. Oxidative degradation of sequence-defined peptoid oligomers

   https://doi.org/10.1039/D2ME00179A  

   Schunk, Hattie C.; Austin, Mariah J.; Taha, Bradley Z.; McClellan, Matthew S.; Suggs, Laura J.; Rosales, Adrianne M. (January 2023, Molecular Systems Design & Engineering)

   Due to their N -substitution, peptoids are generally regarded as resistant to biological degradation, such as enzymatic and hydrolytic mechanisms. This stability is an especially attractive feature for therapeutic development and is a selling point of many previous biological studies. However, another key mode of degradation remains to be fully explored, namely oxidative degradation mediated by reactive oxygen and nitrogen species (ROS/RNS). ROS and RNS are biologically relevant in numerous contexts where biomaterials may be present. Thus, improving understanding of peptoid oxidative susceptibility is crucial to exploit their full potential in the biomaterials field, where an oxidatively-labile but enzymatically stable molecule can offer attractive properties. Toward this end, we demonstrate a fundamental characterization of sequence-defined peptoid chains in the presence of chemically generated ROS, as compared to ROS-susceptible peptides such as proline and lysine oligomers. Lysine oligomers showed the fastest degradation rates to ROS and the enzyme trypsin. Peptoids degraded in metal catalyzed oxidation conditions at rates on par with poly(prolines), while maintaining resistance to enzymatic degradation. Furthermore, lysine-containing peptide–peptoid hybrid molecules showed tunability in both ROS-mediated and enzyme-mediated degradation, with rates intermediate to lysine and peptoid oligomers. When lysine-mimetic side-chains were incorporated into a peptoid backbone, the rate of degradation matched that of the lysine peptide oligomers, but remained resistant to enzymatic degradation. These results expand understanding of peptoid degradation to oxidative and enzymatic mechanisms, and demonstrate the potential for peptoid incorporation into materials where selectivity towards oxidative degradation is necessary, or directed enzymatic susceptibility is desired. 

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4. The effect of thread-like monomer structure on the synthesis of poly[ n ]catenanes from metallosupramolecular polymers

   https://doi.org/10.1039/d2sc05542b  

   Tranquilli, Marissa M.; Rawe, Benjamin W.; Liu, Guancen; Rowan, Stuart J. (March 2023, Chemical Science)

   The main-chain poly[ n ]catenane consists of a series of interlocked rings that resemble a macroscopic chain-link structure. Recently, the synthesis of such intriguing polymers was reported via a metallosupramolecular polymer (MSP) template that consists of alternating units of macrocyclic and linear thread-like monomers. Ring closure of the thread components has been shown to yield a mixture of cyclic, linear, and branched poly[ n ]catenanes. Reported herein are studies aimed at accessing new poly[ n ]catenanes via this approach and exploring the effect the thread-like monomer structure has on the poly[ n ]catenane synthesis. Specifically, the effect of the size of the aromatic linker and alkenyl chains of the thread-like monomer is investigated. Three new poly[ n ]catenanes (with different ring sizes) were prepared using the MSP approach and the results show that tailoring the structure of the thread-like monomer can allow the selective synthesis of branched poly[ n ]catenanes. 

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5. N , N -Disubstituted- N ′-acylthioureas as modular ligands for deposition of transition metal sulfides

   https://doi.org/10.1039/c7dt04860b  

   Ali, Zahra; Richey, Nathaniel E.; Bock, Duane C.; Abboud, Khalil A.; Akhtar, Javeed; Sher, Muhammad; McElwee-White, Lisa (January 2018, Dalton Transactions)

   null (Ed.)

   First row transition metal complexes (Ni, Co, Cu, Zn) with N , N -disubstituted- N ′-acylthiourea ligands have been synthesized and characterized. Bis( N , N -diisopropyl- N ′-cinnamoylthiourea)nickel was found to have the lowest onset temperature for thermal decomposition. Thin film deposition of Ni, Co, and Zn sulfides by aerosol assisted chemical vapor deposition from their respective N , N -diisopropyl- N ′-cinnamoylthiourea complexes at 350 °C has been demonstrated. 

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