The structural characteristics of RNA-peptide (RNP) complexes are suitable for molding of a ligand-binding pocket of the RNP complex in a stepwise manner. The first step involves molding of the RNA subunit by in vitro selection of an RNP pool originating from an RNA library and the peptide, as previously reported for the construction of an ATP-binding RNP complex from an RRE RNA-Rev peptide complex. The second step involves selection from an RNP library consisting of Rev peptides with randomized amino acid residues and the RNA subunit selected in the first molding. The ATP-binding pocket produced by sequential molding of RNA and peptide subunits shows higher affinity to ATP and a distinct specificity for ATP versus dATP as compared to the ATP-binding RNP receptor in which only the RNA subunit has been molded. The second step selection from the peptide-based RNP library allows expansion of the ATP recognition surface, consisting of both RNA and peptide subunits, to enhance the affinity and selectivity to discriminate ATP against dATP. Our approach of stepwise molding offers the advantage of increasing the diversity of the RNP library by utilizing characteristics of different biopolymers. The ribonucleopeptide-based, multi-subunit approach is also extendable to other biomacromolecular assemblies, which may yield artificial receptors and enzymes with increased specificity and more diverse chemical activities.
Polysubstituted isocoumarins such as thunberginol A were synthesized by the reaction of substituted 2-(trimethylsilyl)phenyl triflate with trifluoromethylated β-diketones in the presence of CsF. The reaction proceeded via carbon–carbon bond insertion of aryne followed by intramolecular cyclization and CF3 anion extrusion. The –C(···O)CF3 unit has high potential for not only the nucleophilic moiety but also a useful leaving group of CF3.
2,3-Benzodiazepines were synthesized by two-step or one-pot reactions from aryne precursors. Reaction of 2-(trimethylsilyl)aryl triflates with β-diketones in the presence of CsF gave ortho-substituted benzophenones. Treatment of benzophenones with hydrazine hydrate resulted in the formation of 2,3-benzodiazepines in moderate yields. Tofisopam, a well known anxiolytic, could be synthesized via C–C bond insertion of 3,4-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)butane-1,3-dione, followed by the reaction with hydrazine hydrate in one-pot operation. 2,3-Benzodiazepin-4-ones were also synthesized by the reaction of β-keto esters with triflates in the presence of CsF, followed by the addition of hydrazine hydrate. Substituted isoquinolines were synthesized by the reaction of ortho-substituted benzophenones with ammonium hydroxide.
Novel one-pot synthesis of 2,3-benzodiazepines from aryne precursors was accomplished. Tofisopam, well-known anxiolytics, could be synthesized via C–C bond insertion of 4,5-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)butane-1,3-dione, followed by the reaction with hydrazine hydrate in a one-pot operation. This protocol is applicable to the synthesis of other biologically active 2,3-benzodiazepines, such as Girisopam and Nerisopam.
Polysubstituted isocoumarins were synthesized by the reaction of substituted 2‐(trimethylsilyl)aryl triflates with trifluoromethylated β‐diketones in the presence of CsF. The reaction proceeded through carbon‐carbon bond insertion of aryne and intramolecular cyclization to form intermediates of alcohol anions, which extruded trifluoromethyl anion to afford isocoumarins. By using CuBr as a catalyst, 2 eq. of aryne reacted with β‐diketones to afford phenanthrenes and 1,2‐diarylethanones. Although reaction of 2‐(trimethylsilyl)phenyl triflate with 1,1,1‐trifluoro‐4′‐methylbenzoylacetone in the presence of CsF gave 3‐(4′‐methylphenyl)isocoumarin in 67% yield, addition of 0.2 eq. of CuCN resulted in the formation of 9‐(4‐methylbenzoyl)‐10‐trifluoromethylphenanthrene in 35% yield.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.