In recent years, there has been a growing interest in therapeutic peptides within the pharmaceutical industry with more than 50 peptide drugs on the market, approximately 170 in clinical trials, and ...>200 in preclinical development. However, the current state of the art in peptide synthesis involves primarily legacy technologies with use of large amounts of highly hazardous reagents and solvents and little focus on green chemistry and engineering. In 2016, the ACS Green Chemistry Institute Pharmaceutical Roundtable identified development of greener processes for peptide API as a critical unmet need, and as a result, a new Roundtable team formed to address this important area. The initial focus of this new team is to highlight best practices in peptide synthesis and encourage much needed innovations. In this Perspective, we aim to summarize the current challenges of peptide synthesis and purification in terms of sustainability, highlight possible solutions, and encourage synergies between academia, the pharmaceutical industry, and contract research organizations/contract manufacturing organizations.
A multifunctional fluorescent sensor based on a cyclen-appended BINOL derivative (R-1) was synthesized and characterized. It can display on–off-type fluorescence change with high selectivity toward ...Cu(II) among 19 metal ions in 100% aqueous solution. Furthermore, the in situ generated R-1–Cu(II) ensemble could recover the quenched fluorescence upon the addition of sulfide anion resulting in a off–on-type sensing with a detection limit of micromolar range in the same medium. No interference was observed from other biothiols and anions, including GSH, l-Cys, DTT, and sulfates, making it a highly sensitive and selective sulfide probe.
We used iodo-Bodipy derivatives that show strong absorption of visible light and long-lived triplet excited states as organic catalysts for photoredox catalytic organic reactions. Conventionally most ...of the photocatalysts are based on the off-the-shelf compounds, usually showing weak absorption in the visible region and short triplet excited state lifetimes. Herein, the organic catalysts are used for two photocatalyzed reactions mediated by singlet oxygen (1O2), that is, the aerobic oxidative coupling of amines and the photooxidation of dihydroxylnaphthalenes, which is coupled to the subsequent addition of amines to the naphthoquinones, via C–H functionalization of 1,4-naphthoquinone, to produce N-aryl-2-amino-1,4-naphthoquinones (one-pot reaction), which are anticancer and antibiotic reagents. The photoreactions were substantially accelerated with these new iodo-Bodipy organic photocatalysts compared to that catalyzed with the conventional Ru(II)/Ir(III) complexes, which show weak absorption in the visible region and short-lived triplet excited states. Our results will inspire the design and application of new organic triplet photosensitizers that show strong absorption of visible light and long-lived triplet excited state and the application of these catalysts in photoredox catalytic organic reactions.
In this manuscript, we report the first synthesis of an organic monomolecular emitter, which behaves as a circularly polarized luminescence (CPL)-based ratiometric probe. The enantiopure helical ...ortho-oligo(phenylene)ethynylene (o-OPE) core has been prepared by a new and efficient macrocyclization reaction. The combination of such o-OPE helical skeleton and a pyrene couple leads to two different CPL emission features in a single structure whose ratio linearly responds to silver(I) concentration.
Trifluoromethylseleno substituent (CF3Se) is an emerging group, but its direct introduction onto organic molecules is still quite limited and mainly restricted to nucleophilic methods. Herein, we ...describe a new approach to easily and safely perform electrophilic trifluoromethylselenolation starting from a simple and easily accessible reagent, namely, benzyltrifluoromethyl selenide. This strategy can be generalized to various fluoroalkylselanyl groups, even functionalized ones.
Visible light-harvesting C60–bodipy dyads were devised as universal organic triplet photosensitizers for triplet–triplet annihilation (TTA) upconversion. The antennas in the dyad were used to harvest ...the excitation energy, and then the singlet excited state of C60 will be populated via the intramolecular energy transfer from the antenna to C60 unit. In turn with the intrinsic intersystem crossing (ISC) of the C60, the triplet excited state of the C60 will be produced. Thus, without any heavy atoms, the triplet excited states of organic dyads are populated upon photoexcitation. Different from C60, the dyads show strong absorption of visible light at 515 nm (C-1, ε = 70400 M–1 cm–1) or 590 nm (C-2, ε = 82500 M–1 cm–1). Efficient intramolecular energy transfer from the bodipy moieties to C60 unit and localization of the triplet excited state on C60 were confirmed by steady-state and time-resolved spectroscopy as well as DFT calculations. The dyads were used as triplet photosensitizers for TTA upconversion, and an upconversion quantum yield up to 7.0% was observed. We propose that C60–organic chromophore dyads can be used as a general molecular structural motif for organic triplet photosensitizers, which can be used for photocatalysis, photodynamic therapy, and TTA upconversions.
A novel and efficient palladium-catalyzed cascade annulation/arylthiolation reaction has been developed to afford functionalized 3-sulfenylbenzofuran and 3-sulfenylindole derivatives in moderate to ...good yields from readily available 2-alkynylphenols and 2-alkynylamines in ionic liquids. This protocol provides a valuable synthetic tool for the assembly of a wide range of 3-sulfenylbenzofuran and 3-sulfenylindole derivatives with high atom- and step-economy and exceptional functional group tolerance. Moreover, the employment of ionic liquids under mild reaction conditions makes this transformation green and practical. Furthermore, this approach enriched current C–S bond formation chemistry, making a valuable and practical method in synthetic and medicinal chemistry.
Specific chemical reactions by enzymes acting on a nucleobase are realized by flipping the target base out of the helix. Similarly, artificial oligodeoxynucleotides (ODNs) can also induce the base ...flipping and a specific chemical reaction. We now report an easily prepared and unique structure-providing photo-cross-linking reaction by taking advantage of the base-flipping-out field formed by alkene-type base-flipping-inducing artificial bases. Two 3-arylethenyl-5-methyl-2-pyridone nucleosides with the Ph or An group were synthesized and incorporated into the ODNs. We found that the two Ph derivatives provided the cross-linked product in a high yield only by a 10 s photoirradiation when their alkenes overlap each other in the duplex DNA. The highly efficient reaction enabled forming a cross-linked product even when using the duplex with a low T m value.
Design and synthesis of a novel tetraphenylethene–2-pyrone (TPEP) conjugate exhibiting donor–acceptor characteristics is reported. The localized frontier molecular orbitals (DFT studies) and the ...solvent polarity dependent photoluminescence characteristics directly corroborate the presence of intramolecular charge transfer character in TPEP. TPEP is poorly emissive in the solution state. In contrast, upon aggregation (THF/water mixtures), TPEP exhibits aggregation-induced emission enhancement. Upon aggregation, dyad TPEP forms a fluorescent nanoaggregate which was confirmed by transmission electron microscopy imaging studies. The luminescence nanoaggregates were elegantly exploited for selective detection of nitro aromatic compounds (NACs). It was found that nanoaggregates of TPEP were selectively sensing the picric acid over the other NACs. Efficiency of the quenching process was further evaluated by the Stern–Volmer equation. TPEP-based low-cost fluorescent test strips were developed for the selective detection of picric acid.
A gram-scale syn-selective asymmetric vinylogous addition of butenolides to chromones, catalyzed by an Al-Li-BINOL (ALB) complex, was developed in this study. For various combinations of substrates, ...the observed diastereoselectivity approached 20:1 with 84–98% ee. This protocol is complementary to previously reported ones and improves the selectivity for several chromones. This methodology can be applied to a quinolone substrate, affording another type of heterocyclic scaffolds substituted with five-membered lactones. Computational studies support the role of ALB as a bifunctional catalyst in this reaction and provide insights into the origin of the observed stereoselectivity.
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