January 2022

Polyampholyte hydrogels have shown promise as functional biomaterial platforms with resistance to nonspecific protein adsorption (nonbiofouling). Yet there are few zwitterionic cross-linkers available to complement these materials and to provide an extended charge density throughout the 3D network. The recent development of peptide-based zwitterionic cross-linkers has shown merit. Indeed, the use of functionalizable amino acids permits the synthesis of a series of peptide-based zwitterionic methacrylate and methacrylamide cross-linkers. Methacrylate additions prior to peptide coupling provide an outside-in strategy when using natural l-serine or l-lysine as substrates to produce a series of methacrylate and methacrylamide combinations, expanding the library of peptide-based cross-linkers. Here, we describe the preparation of such dipeptide combinations as Ser-Lys, Lys-Ser, and Lys-Lys in zwitterionic bis(methacrylate/methacrylamide) cross-linkers. To highlight the utility of this method and its potential to increase the distance between zwitterionic components, syntheses of the tripeptide Lys-Gly-Lys dimethacrylamide and Ser-Gly-Ser dimethacrylate are reported.

A new general process for constructing ortho-tert-butyl phenols is presented within the context of other known methods. All are briefly evaluated with regards to regioselectivity, efficiency, and functional group tolerance. In addition, we present an assortment of tert-butyl substrates accessed through o-QM chemistry. Our conclusion is that the o-QM process provides greater yields, flexibility, and generality than most other known methods for delivering ortho-tert-buytlated phenols and their derivatives.1 Introduction2 Friedel–Crafts Alkylation3 Addition of t-Bu– or t-Bu• to Carbonyl Compounds4 ipso-SNAr Reactions of Aryl Methoxy and tert-Butylsulfoxide Moieties5 Metal-Mediated Coupling of Aryl Bromides6 Applications of o-Quinone Methides (o-QMs)7 Conclusion

A cascade reaction of 3-phenacylideneoxindoles with trimethylsilyl cyanide is described. This method provides an efficient route for the synthesis of furan-fused 1,3-benzodiazepin-2-one derivatives by simply refluxing a reaction mixture of various 3-phenacylideneoxindoles with trimethylsilyl cyanide in the presence of H2O and K2CO3.

Reductive radical cyclizations are ubiquitous in organic synthesis and have been applied to the synthesis of structurally complex molecules. N-Heterocyclic motifs can be prepared through the cyclization of α-haloamides; however, slow rotation around the amide C–N bond results in preferential formation of an acyclic hydrodehalogenated product. Here, we compare four different methods for preparing γ-, δ-, ε-, and ζ-lactams via radical cyclization. We found that a photoenzymatic method using flavin-dependent ‘ene’ reductases affords the highest level of product selectivity. We suggest that through selective binding of the cis-amide isomer, the enzyme preorganizes the substrate for cyclization, helping to avoid premature radical termination.