Synthesis and Spectroscopic Properties of Rosamines with Cyclic Amine Substituents

Abstract

There is a close structural similarity between rosamines A and rhodamines B, yet a diversity of structures in the rosamine class and their spectral properties have yet to be explored in depth. This manuscript describes a concise, scalable, solution-phase method to obtain rosamines 1-5 and 12-15, which include some water-soluble derivatives. In one test case (for 15) an illustrative protein conjugate was also formed. Throughout these products were isolated and purified, and the syntheses were found to be scalable. Further, the rosamines with these cyclic amine substituents display solvent-dependent fluorescence intensities, and high quantum yields in chlorinated hydrocarbons. In some cases the nature of the cyclic amine substituent was shown to modulate the fluorescence of the parent molecules in pH-dependent ways. The ring size of those amine substituents also correlated with some of their spectroscopic properties. Several water-soluble rosamines were prepared from some of the addition products 1-5, and one of these, 15, was efficiently conjugated to avidin via an amide linkage. The spectroscopic properties of 15 and 15-avidin in aqueous media were very similar.

New cytotoxic rosamine derivatives selectively accumulate in the mitochondria of cancer cells

“…Although both compounds 10 and 11 have equally potent antiproliferative activity with similar IC 50 values in the low submicromolar range, the fluorescence quantum yield of compound 10 is low, at a value that is approximately 3-fold lower compared with compound 11 (0.28 ± 0.01 vs. 0.10 ± 0.01 in ethanol) [16]. Therefore, only the intracellular localization of compound 11 in HSC2 cells was examined by confocal microscopy using dual-staining techniques (Fig.…”

“…The rosamine derivatives studied here with cyclic amine substituents were part of a new class of fluorescent molecules [16]. They were prepared in solution by S N Ar reactions of a relatively accessible xanthone ditriflate, followed by substitution of the triflate with cyclic amines.…”

Rational Design of a Ratiometric Fluorescent Probe Based on Arene–Metal‐Ion Contact for Endogenous Hydrogen Sulfide Detection in Living Cells

“…Thes ynthetic route to the pyronine-type ligand 6 is given in Scheme3.B riefly,t he 4,7-dihydroxyxanthone 9 obtained from 8 [12a] by deprotection of the pivaloyl groups was converted to ditriflate 10,which was treated with pyrrolidine to give the 4,7-diaminoxanthone 11. [14] After reduction with borane-dimethylsulfide complex, 12 was oxidized by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)t oa fford pyronine 13.F inally,d eprotection of tert-butyl esters and subsequentH PLC purification provided the pure ligand 6.T he photophysical properties of the ligandsa nd their Cd II complexes are summarized in Ta ble S1. In CdCl 2 titration ( Figure S4) www.chembiochem.org large emission blue shifts upon the addition of sodiums ulfide (Na 2 S) as ad onor of H 2 S, leading to changes in the fluorescence ratio value R,a ss hown in Figure 2B and C. Simultaneously,t he absorption spectra of the probes wereh ypsochromically shifted ( Figure S5);t his suggests that the emission shifts were induced by the loss of AM-contact as ar esult of the release of Cd II -free ligands.…”

“…As olution of 10 (400 mg, 0.4 mmol) and pyrrolidine (368 mL, 4.49 mmol) in dry DMSO (5 mL) was stirred at 90 8C for 15 h. [14] After being cooled to RT,the reaction mixture was diluted with CHCl 3 and washed with saturated NaHCO 3 ,t hen dried over Na 2 SO 4 .A fter removal of the solvent in vacuo, the residue was purified by flash column chromatography on silica gel (CHCl 3 / MeOH 60:1) to give 11 (68.5 mg, 20 %) as aw hite powder. Synthesis of 12:Asolution of 11 (40.6 mg, 48 mmol) in dry THF (6 mL) was added dropwise to as olution of borane dimethylsulfide complex (485 mL, 0.96 mmol) in dry THF (0.48 mL).…”

Coumarin‐Caged Rosamine Probes Based on a Unique Intramolecular Carbon–Carbon Spirocyclization

“…Structurally, in comparison to rhodamines, rosamines lack a carboxylic acid functional group. [12] Thus, the traditional rhodamine caging method is not applicable for rosamines, since they can not lactonize to turn off the fluorescence due to the lack of a carboxylic acid group. To the best of our knowledge, rosamines have not been successfully caged yet.…”