No abstract

A visible-light-induced method for the construction of heterocyclic scaffolds such as pyrido[1,2-a]indoles and indolizines via sulfonyl radical-triggered relay cyclization without employing any external photocatalyst has been developed. Preliminary mechanistic investigation indicated that indole and pyrrole derivatives could serve as pre-photocatalysts to promote the sulfonylation/cyclization, thereby providing a facile method to synthesize valuable sulfonylated heterocycles.

Boron neutron capture therapy (BNCT) is a promising cancer treatment strategy that utilizes boron-containing ligands. In this report, a series of substituted boramino acids were synthesized and evaluated, aiming to obtain metabolically stable boron-derived agents that could integrate positron emission tomography (PET) with BNCT (a theranostic agent). Based on the phenylalanine (Phe) core structure, the impact of substitution groups on tumor accumulation was studied. The agents were labeled with fluorine-18 in 27.2−66.8% yield via the 18 F− 19 F isotope exchange reaction. In B16-F10 tumor-bearing mice,demonstrated the best tumor uptake (5.54 ± 2.32% ID/g based on ex vivo biodistribution and 3.5 ± 0.04% ID/g based on PET imaging with the tumor-to-muscle ratio up to 2.6) and stability compared with other tested agents. Together, R-[ 18 F]-5a is a promising agent that could potentially integrate PET and BNCT, whose treatment efficacy is worth further evaluation in the future.

Although various radiolabeled tryptophan analogs have been developed to monitor tryptophan metabolism using positron emission tomography (PET) for various human diseases including melanoma and other cancers, their application can be limited due to the complicated synthesis process. In this study, we demonstrated that photoredox radiofluorination represents a simple method to access novel tryptophan-based PET agents. In brief, 4-F-5-OMe-tryptophans (L/D-T13) and 6-F-5-OMe-tryptophans (L/D-T18) were easily synthesized. The 18 F-labeled analogs were produced by photoredox radiofluorination with radiochemical yields ranging from 2.6 ± 0.5% to 32.4 ± 4.1% (3 ≤ n ≤ 5, enantiomeric excess ≥ 99.0%) and over 98.0% radiochemical purity. Small animal imaging showed that L-[ 18 F]T13 achieved 9.58 ± 0.26%ID/g tumor uptake and good contrast in B16F10 tumor-bearing mice (n = 3). Clearly, L-[ 18 F]T13 exhibited prominent tumor uptake, warranting future evaluations of its potential usage in precise immunotherapy monitoring.