Diverse 3-Methylthio-4-Substituted Maleimides through a Novel Rearrangement Reaction: Synthesis and Selective Cell Imaging

Abstract

A transition metal-free protocol for the preparation of fluorescent and non-fluoresent 3-methylthio-4-arylmaleimides in a single step through a new rearrangement from thiazolidine-2,4-diones is described. By employing the optimized reaction conditions, a broad scope of derivatives was prepared in ≤97% yield. The reaction tolerated several substituted aryl groups, including the challenging preparation of pyridyl-containing derivatives. A series of control experiments strongly suggested that the new rearrangement involves a key isocyanate intermediate and a further reaction with in situ-generated methylthiomethyl acetate. The photophysical properties of some of the synthesized derivatives as well as their use in live cell imaging were also investigated, revealing that some of the substituted maleimides are capable of selectively staining different regions of the cells.

Novel NO-TZDs and trimethoxychalcone-based DHPMs: design, synthesis, and biological evaluation as potential VEGFR-2 inhibitors

“…Scheme 1 demonstrates the synthetic pathway of target compounds NO-TZD-3a-d and NO-TZD-5 . Condensation of TZD-1 with different aldehydes in absolute ethanol containing 0.8 equivalent of piperazine 42–44 provided the key intermediates TZDs 2a-d and 4 43 , 45 , 46 which underwent N -alkylation with furoxan mesylate in DMF containing potassium carbonate at 65 °C to yield NO-TZD-3a-d and NO-TZD-5 . On the other hand, O -allylation of NO-TZD-3c with allyl bromide in DMF containing potassium carbonate at 80 °C afforded the allyl derivative NO-TZD-6 ( Scheme 2 ).…”

“…On the other hand, O -allylation of NO-TZD-3c with allyl bromide in DMF containing potassium carbonate at 80 °C afforded the allyl derivative NO-TZD-6 ( Scheme 2 ). Since the chemical shift of the exocyclic olefinic proton in the ( Z )-isomer is relatively deshielded rather than the ( E )-one, the Z -configuration of TZDs was verified by comparing with the incremented chemical shifts 43 , 45–47 . Hence, the existence of singlet signal corresponding to the vinylic proton at 7.93–8.09 ppm demonstrates the Z -configuration of TZDs.…”

“…All reagents and solvents were acquired from commercially available suppliers. The intermediates TZD-1 76 , 77 , TZD-2a-d 43 , 45 , 46 , TZD-4 43 , DHPM-7a-g 48–53 , C-8 48–53 , C-9 56–58 were prepared as previously described.…”

Recent Advances in N-Heterocyclic Small Molecules for Synthesis and Application in Direct Fluorescence Cell Imaging

“…Recently, Amarante and co-workers reported a transition metal-free approach to obtain maleimide derivative 25 through a novel rearrangement from thiazolidine-2,4-diones in one step [ 62 ]. N -butylmaleimide 26 was obtained through a substitution reaction of compound 25 and 1-bromobutane ( Scheme 21 ).…”